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What's new in oncology
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What's new in oncology
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Jun 2017. | This topic last updated: Jul 20, 2017.

The following represent additions to UpToDate from the past six months that were considered by the editors and authors to be of particular interest. The most recent What's New entries are at the top of each subsection.

BREAST CANCER

Risks of breast and ovarian cancer among BRCA mutation carriers (June 2017)

In a prospective cohort study of over 9800 female BRCA mutation carriers, cumulative rates of breast and ovarian cancer until age 80 years were 72 and 44 percent for BRCA1 carriers and 69 and 17 percent for BRCA2 carriers, respectively [1]. In addition to educating women regarding their genetic risk factors, we also counsel women on how other risk modifiers, including reproductive history, use of hormonal therapy, and oophorectomy status, may impact their lifetime cancer risks. (See "Prevalence of BRCA1 and BRCA2 mutations and associated cancer risks", section on 'Breast and ovarian cancer' and "Prevalence of BRCA1 and BRCA2 mutations and associated cancer risks", section on 'Nongenetic cancer risk modifiers'.)

Olaparib in BRCA-associated, HER2-negative breast cancer (June 2017)

The role of poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors in metastatic breast cancer is being investigated. In the phase III OlympiAD trial, over 300 patients with metastatic HER2-negative, BRCA-associated breast cancer with disease progression despite chemotherapy were randomly assigned to the PARP inhibitor olaparib or to chemotherapy [2]. Progression-free survival (PFS) was longer for the PARP group (7.0 versus 4.2 months), with fewer toxicities. Overall survival data are not yet mature. In the setting of evolving data, some UpToDate contributors offer olaparib to those with metastatic HER2-negative, BRCA-associated breast cancer that has progressed on previous therapies, while others await further survival data prior to suggesting this therapy. (See "Systemic treatment for metastatic breast cancer: General principles", section on 'Special considerations for BRCA carriers'.)

Nonanthracycline-based regimens in the neoadjuvant treatment of HER2-positive breast cancer (June 2017)

Although efficacy of anthracycline or nonanthracycline-based regimens is similar in the adjuvant setting for patients with local HER2-positive breast cancer, data in the neoadjuvant setting are limited. In a phase III trial of over 400 patients with stage II to III HER2-positive breast cancer randomly assigned to nonanthracycline- or anthracycline-based neoadjuvant chemotherapy with concurrent pertuzumab and trastuzumab, the rates of pathologic complete response rate (pCR) did not differ between the arms (67 versus 68 percent, respectively) [3]. Rates of febrile neutropenia and decline in left ventricular ejection fraction were higher among those receiving anthracyclines. These data support our approach of offering nonanthracycline-based chemotherapy, together with HER2-directed therapy, to women receiving neoadjuvant treatment for HER2-positive breast cancer. (See "Neoadjuvant therapy for patients with HER2-positive breast cancer", section on 'Nonanthracycline-based treatment'.)

Adjuvant pertuzumab for HER2-positive breast cancer (June 2017)

While pertuzumab has shown benefit in the neoadjuvant setting for high-risk HER2-positive breast cancer, its role in the adjuvant setting is just now emerging. In the phase III APHINITY trial, over 4800 patients with HER2-positive breast cancer who were treated with adjuvant chemotherapy and trastuzumab were randomly assigned to pertuzumab (concurrent with trastuzumab) or placebo [4]. At a median follow-up of approximately 45 months, patients receiving pertuzumab had higher three-year invasive disease-free survival rates (94 versus 93 percent), with the greatest benefit for those with node-positive disease. Given this trial, we now suggest the addition of adjuvant pertuzumab for women with node-positive disease or larger, node-negative tumors (>2 cm). However, some patients may reasonably choose against additional treatment, given the added toxicities of pertuzumab and lack of demonstrated overall survival benefit. (See "Adjuvant systemic therapy for HER2-positive breast cancer", section on 'Addition of pertuzumab for high-risk disease'.)

Adjuvant capecitabine for residual HER2-negative breast cancer after neoadjuvant chemotherapy (June 2017)

In a randomized trial of approximately 900 patients with HER2-negative breast cancer and residual disease after neoadjuvant chemotherapy, patients in the adjuvant capecitabine group, compared with placebo, had higher rates of five-year disease-free survival (74 versus 68 percent) and overall survival (89 versus 84 percent) [5]. Subgroup analyses suggested that these findings were driven primarily by outcomes in patients with triple-negative disease. Toxicities were higher in patients receiving capecitabine, including diarrhea, neutropenia, and hand-foot syndrome. Given these results, we now suggest capecitabine for patients with residual HER2-negative breast cancer after neoadjuvant therapy, though observation is also acceptable, given the increased toxicities associated with adjuvant capecitabine. (See "Adjuvant chemotherapy for HER2-negative breast cancer", section on 'Patients who received neoadjuvant treatment'.)

Adjuvant bisphosphonates in early breast cancer (April 2017)

Although there are clear indications for bisphosphonates for women with breast cancer and decreased bone mineral density, use of bisphosphonates to improve cancer outcomes is more controversial. Studies have shown a small but consistent mortality benefit with adjuvant bone modifying therapy in postmenopausal women with early breast cancer [6,7]. The absolute benefits are small, however, and studies of the effectiveness of adjuvant bisphosphonate therapy are ongoing. Based on currently available data and recent guidelines from the American Society of Clinical Oncology (ASCO) and Cancer Care Ontario (CCO) [7], we offer adjuvant bisphosphonate therapy to postmenopausal women deemed to be at moderate to high risk of breast cancer recurrence. (See "Overview of the use of osteoclast inhibitors in early breast cancer", section on 'Impact on breast cancer outcomes'.)

Adjuvant trastuzumab in early HER2-positive breast cancer (February 2017)

In the Herceptin Adjuvant (HERA) trial, over 5000 women with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer who had completed adjuvant chemotherapy were randomly assigned to observation or to the addition of trastuzumab for one or two years [8-11]. In the final report of this study, at a median of 11 years of follow-up, one year of trastuzumab improved disease-free and overall survival relative to observation [9]. There were no further improvements with extension to two years of trastuzumab, but the incidence of cardiotoxicity was higher. These results support our approach of administering adjuvant trastuzumab for one year to those with HER2-positive early breast cancer. (See "Adjuvant systemic therapy for HER2-positive breast cancer", section on 'Treatment duration'.)

Duration of adjuvant endocrine therapy for breast cancer (July 2016, Modified February 2017)

For postmenopausal women receiving adjuvant treatment with an aromatase inhibitor (AI) for hormone-positive breast cancer, the minimum duration of treatment is five years. While data from the MA17R trial demonstrated that extending the duration from 5 to 10 years improved recurrence-free survival [12], preliminary results from the NSABP-B42, DATA, and IDEAL trials, reported at the San Antonio Breast Cancer Symposium, have not confirmed this benefit [13-15]. No study has demonstrated a benefit in overall survival with extended adjuvant AI therapy, and bone-related toxic effects are more frequent among those receiving extended treatment. While variations in methodology likely account for the differences in recurrence-free survival between the studies, the magnitude of any potential benefit is likely to be greatest for those at highest risk for recurrence. While we previously had recommended an extended course of AI adjuvant therapy for most postmenopausal women with nonmetastatic hormone-positive disease, based on the new data, we now suggest offering extended adjuvant aromatase inhibitor therapy to those with high-risk disease (eg, node-positive or ≥T3 disease). (See "Adjuvant endocrine therapy for non-metastatic, hormone receptor-positive breast cancer", section on 'Duration of endocrine treatment'.)

CANCER SCREENING AND PREVENTION

Risk of colon cancer in patients with diverticulitis (April 2017)

The utility of routine colonoscopy after acute diverticulitis is debated. An analysis of data from a Danish registry showed that patients hospitalized for diverticulitis were twice as likely to develop colon cancer over the 18-year study period as those without diverticulitis, and over 50 percent of colon cancers were diagnosed within one year of diagnosis of diverticulitis [16]. This study underscores the importance of endoscopic surveillance in patients with diverticular disease and supports our recommendation for performing a colonoscopy after the complete resolution of an episode of acute diverticulitis in patients who have not had a colonoscopy within a year. (See "Acute colonic diverticulitis: Medical management", section on 'Colonoscopy for all patients'.)

Vitamin D and prevention of cancer (April 2017)

In a trial comparing the effect of vitamin D and calcium supplementation with placebo on the incidence of cancer in over 2000 postmenopausal women, there was no difference between groups in the incidence of cancer at four years [17]. An analysis by cancer site showed no difference in the incidence of breast cancer between the two groups; there were too few cancers at other sites to analyze. Although several study limitations may have contributed to the absence of an effect, including enrollment of patients with a relatively high baseline vitamin D level and permission to take vitamin D supplements (up to 800 international units daily) outside of the intervention, vitamin D supplementation for the prevention of cancer is not warranted. (See "Vitamin D and extraskeletal health", section on 'Cancer'.)

Flexible sigmoidoscopy and colorectal cancer screening in older women (January 2017)

Flexible sigmoidoscopy is one of several screening modalities recommended by the US Preventive Services Task Force for colorectal cancer (CRC) screening. However, sigmoidoscopy is less effective at detecting lesions in the right side of the colon (beyond the 60 cm reach of the sigmoidoscope) than the left side, and right-sided lesions are more common in older women. A study that pooled results from three randomized trials (nearly 300,000 individuals) comparing screening by sigmoidoscopy with no screening found that the incidence of CRC at 10 to 12 years was decreased in men but, in women, only in those younger than 60 years [18]. Current screening recommendations do not indicate gender-based preferences for screening options, but these findings call into question the effectiveness of flexible sigmoidoscopy as a screening modality for women over age 60 years. (See "Tests for screening for colorectal cancer: Stool tests, radiologic imaging and endoscopy", section on 'Evidence of effectiveness' and "Screening for colorectal cancer: Strategies in patients at average risk", section on 'Comparison of tests'.)

Fecal immunochemical testing for colorectal cancer screening (January 2017)

Multiple test strategies are available for screening in people with average risk for colorectal cancer (CRC). Annual stool testing for occult blood using a guaiac reagent (gFOBT) has been widely implemented and is one of the screening strategies endorsed by the US Preventive Services Task Force. Fecal immunochemical testing (FIT) is another option and has the potential advantages of better test performance (improved sensitivity for CRC and advanced adenomas) and better patient adherence (one stool sample, no diet restrictions) compared with gFOBT. The US Multi-Society Task Force has published consensus guidelines recommending FIT over gFOBT when occult blood stool testing is elected for CRC screening [19]. (See "Tests for screening for colorectal cancer: Stool tests, radiologic imaging and endoscopy", section on 'Immunochemical tests for fecal blood' and "Screening for colorectal cancer: Strategies in patients at average risk", section on 'Comparison of tests'.)

Effectiveness of screening colonoscopy in older adults (January 2017)

The effectiveness of screening for colorectal cancer (CRC) in older adults is uncertain. Randomized trials of screening colonoscopy have not been completed, and trials currently underway do not include adults 75 years and older. A study of Medicare beneficiaries found that undergoing colonoscopy believed to be for screening modestly decreased the risk of CRC (2.2 versus 2.6 percent in the no-screening group) over an eight-year period for those aged 70 to 74 years, with a smaller, but statistically non-significant, decrease in risk (2.8 versus 3.0 percent in the no-screening group) for those 75 to 79 years [20]. Adverse events following colonoscopy occurred in less than 1 percent. The decision whether to recommend screening for a patient at any age, but especially those over 75 years of age, should depend upon the patient's health status, anticipated life expectancy, risk for colorectal cancer (CRC), and personal values. (See "Screening for colorectal cancer: Strategies in patients at average risk", section on 'Screening in older adults'.)

GASTROINTESTINAL CANCER

Duration of adjuvant oxaliplatin for stage III colon cancer (July 2017)

Six months of oxaliplatin-based chemotherapy has been standard adjuvant treatment for stage III colon cancer, but associated neuropathy has prompted interest in shorter treatment. In preliminary results from a pooled analysis of over 12,000 patients with stage III colon cancer from six trials comparing three versus six months of treatment, there was less neuropathy, and the absolute decrement in three-year disease-free survival (DFS) with three months of treatment was very small (<1 percent) [21]. Noninferiority for shorter treatment was supported for earlier substages of disease (T1-3, N1) but not T4 or N2 disease (table 1). These data are preliminary, and overall survival results are not mature. In the interim, we continue to suggest six months of oxaliplatin-based therapy for high-risk disease (T4, N2), but it seems reasonable to limit adjuvant therapy to three months in patients with low-risk disease (T1-3, N1). Patients with low-risk disease who place a high value on minimizing the risk of a disease recurrence may still choose six months of therapy, with oxaliplatin doses adjusted based upon neurotoxicity. Patients with higher-risk disease who place a higher value on avoiding neurotoxicity may choose three months of therapy if they are willing to accept a small potential detriment in DFS. (See "Adjuvant therapy for resected stage III (node-positive) colon cancer", section on 'Duration of therapy'.)

Lenvatinib for advanced hepatocellular cancer (July 2017)

The benefits of first-line sorafenib for advanced hepatocellular cancer (HCC) are modest. A randomized noninferiority trial (the REFLECT study) compared lenvatinib versus sorafenib in over 900 patients with unresectable HCC and no prior systemic therapy [22]. In a preliminary report presented at the 2017 annual meeting of the American Society of Clinical Oncology (ASCO), lenvatinib was noninferior in terms of median overall survival, and both the objective response rate and time to tumor progression were significantly better. Rates of grade 3 or 4 hypertension were higher with lenvatinib, while hand-foot skin reaction was more frequent with sorafenib. Lenvatinib represents a reasonable first-line treatment alternative to sorafenib, especially for patients who cannot tolerate sorafenib. (See "Systemic treatment for advanced hepatocellular carcinoma", section on 'Lenvatinib'.)

Optimal timing of reoperation for gallbladder cancer incidentally found at cholecystectomy (May 2017)

When gallbladder cancer is diagnosed incidentally after cholecystectomy, most patients require a second operation to remove residual disease. In a retrospective analysis of the optimal timing of reoperation by the US Extrahepatic Biliary Malignancy Consortium, reoperation four to eight weeks after the initial cholecystectomy was associated with improved overall survival compared with earlier or later reoperation [23]. This finding requires prospective validation before we would routinely recommend scheduling reoperation four to eight weeks after initial surgery. In practice, timing reoperation may also be influenced by nonclinical factors, such as access to a qualified surgeon or center. (See "Surgical management of gallbladder cancer", section on 'Identified by pathology'.)

Laparoscopic versus open surgery for rectal cancer (May 2017)

Transabdominal rectal cancer surgery can be performed via open, laparoscopic, or robotic approaches. In a systematic review and meta-analysis of 14 randomized trials, laparoscopic surgery resulted in a higher rate of noncomplete total mesorectal excision than open surgery (13 versus 10 percent) [24]. Other technical outcomes were not different. Long-term data are needed to determine whether the higher rate of noncomplete total mesorectal excision will result in worse survival. In the absence of these data, the best surgical approach needs to be determined individually by tumor and patient characteristics, as well as surgeon experience. (See "Rectal cancer: Surgical principles", section on 'Laparoscopic versus open approach'.)

Regorafenib for second-line treatment of advanced hepatocellular cancer (April 2017)

In a randomized trial, regorafenib was shown to provide benefit as a second-line agent for patients with advanced hepatocellular cancer (HCC) and Child-Pugh A liver function who progressed after receiving sorafenib [25]. Compared with placebo, regorafenib significantly improved median overall survival, and the main toxicities were hypertension, hand-foot skin reaction, fatigue, and diarrhea. Largely based upon these data, in April 2017, the US Food and Drug Administration expanded the indications for regorafenib to include patients with HCC previously treated with sorafenib. While optimal patient selection has not been established, a trial of regorafenib is reasonable for patients progressing after first-line sorafenib who maintain a good performance status and adequate liver function, and who are willing to trade treatment-related morbidity for the possibility of a small gain in survival. (See "Systemic treatment for advanced hepatocellular carcinoma", section on 'Regorafenib'.)

Guideline on use of molecular markers in colorectal cancer (April 2017)

The prognostic value of a wide variety of potentially clinically applicable molecular markers has been extensively studied in colorectal cancer (CRC). An updated multisociety United States guideline recommends testing for DNA mismatch repair protein (MMR) status to identify patients at high risk for Lynch syndrome, expanded or extended RAS testing for patients being considered for therapy targeting the epidermal growth factor receptor (EGFR), and BRAF V600 mutational analysis for deficient MMR tumors with loss of MLH1 expression to evaluate for Lynch syndrome risk [26]. They also concluded that there was insufficient evidence to use BRAF mutational status as a predictive molecular biomarker for response to anti-EGFR therapies. However, this is a controversial area. UpToDate recommends not using EGFR inhibitors in patients with a tumoral BRAF V600E mutation. (See "Pathology and prognostic determinants of colorectal cancer", section on 'Molecular factors'.)

ASCO guideline update for adjuvant chemotherapy in pancreatic cancer (April 2017)

A focused clinical practice guideline update for potentially curable pancreatic cancer has been issued by the American Society of Clinical Oncology (ASCO) [27]. For most patients, six months of adjuvant chemotherapy using a doublet regimen of capecitabine plus gemcitabine is preferred over gemcitabine alone, in the absence of concerns for toxicity or tolerance. Treatment should be initiated within eight weeks of resection, assuming complete surgical recovery. This guideline update supports our prior recommendation for doublet therapy. (See "Treatment for potentially resectable exocrine pancreatic cancer", section on 'Choice of therapy'.)

Open versus laparoscopic resection for stage II or III colon cancer (March 2017)

In a trial involving over 1000 patients with stage II or III colon cancer, colon resection performed with complete mesocolic excision and central vascular ligation resulted in equally excellent five-year survivals (over 90 percent) whether surgery was performed open or laparoscopically [28]. Thus, surgeons treating colon cancer have a choice of techniques, but must follow strict oncologic principles, including complete mesocolic excision, to ensure optimal outcomes. (See "Surgical resection of primary colon cancer", section on 'Regional lymphadenectomy'.)

Telotristat for refractory carcinoid syndrome diarrhea (March 2017)

Telotristat inhibits the production of serotonin by carcinoid tumors and reduces the frequency of carcinoid syndrome diarrhea. The randomized TELESTAR trial compared two doses of oral telotristat (250 mg and 500 mg, each taken three times daily) against placebo in 135 patients who had uncontrolled symptoms from carcinoid syndrome despite treatment with a somatostatin analog [29]. Treatment with telotristat at either dose was associated with a reduction in bowel movement frequency compared with placebo, and the drug was well tolerated. Based upon these results, telotristat has been approved in the United States, in combination with somatostatin analog therapy, for the treatment of adults with diarrhea related to carcinoid syndrome that is inadequately controlled by somatostatin analog therapy alone [30]. The recommended dose is 250 mg three times daily [31]. (See "Treatment of the carcinoid syndrome", section on 'Telotristat'.)

Assessing response to chemoradiotherapy in anal cancer (February 2017)

An analysis of data from the ACT II trial supports the view that anal squamous cell cancers (SCCs) continue to regress for up to 26 weeks after the completion of chemoradiotherapy and that the decision to pursue surgery for persisting disease is best deferred until then [32]. The complete clinical response (cCR) rate increased over time, and 72 percent of those not in a cCR at 11 weeks achieved it at 26 weeks. Furthermore, the greatest separation in long-term outcomes between responders and nonresponders occurred when the assessment was delayed until 26 weeks. Based upon these results, we agree with updated guidelines from the National Comprehensive Cancer Network recommending that patients can be watched for up to six months following completion of chemoradiotherapy as long as there is no progressive disease during this period of follow-up. (See "Clinical features, staging, and treatment of anal cancer", section on 'Assessing the response to primary chemoradiotherapy'.)

GENITOURINARY ONCOLOGY

PIVOT trial of surgery versus observation in localized prostate cancer (July 2017)

The PIVOT trial randomly assigned men with localized prostate cancer to radical prostatectomy or observation [33]. After a median follow-up of 12.7 years, the difference in the overall risk of death (61 and 67 percent for surgery and observation, respectively) was not statistically significant; only 9 percent of all deaths were due to prostate cancer. Additional treatment for prostate cancer was eventually required in 34 percent of those managed with radical prostatectomy and 60 percent of those managed with observation. Both erectile dysfunction and urinary incontinence were more frequent with radical prostatectomy. (See "Radical prostatectomy for localized prostate cancer", section on 'Survival impact of radical prostatectomy'.)

Abiraterone/prednisone plus ADT for prostate cancer (June 2017)

Abiraterone blocks the conversion of steroid precursors to androgenic steroids within prostate cancer cells, thus providing the rationale for combining ADT with abiraterone. Two large trials demonstrated that the combination of abiraterone plus androgen deprivation therapy (ADT) prolongs overall survival, compared with ADT alone, in patients with castration-sensitive disease [34,35]. For men with high-risk advanced or metastatic prostate cancer, we recommend that ADT be combined with abiraterone or with docetaxel, as either combination prolongs overall survival compared with ADT monotherapy. The choice of regimen should include a discussion with the patient of the potential toxicities associated with each agent. (See "Initial systemic therapy for castration-sensitive prostate cancer", section on 'ADT plus abiraterone'.)

Adjuvant therapy and resected renal cell carcinoma (June 2017)

The role of adjuvant therapy following complete resection of renal cell carcinoma (RCC) has been unclear, with conflicting results from two previous trials using sunitinib and sorafenib. In an initial report from the PROTECT trial in patients with completely resected RCC, there was no difference in disease-free survival comparing adjuvant pazopanib with placebo [36]. Except for patients enrolled in a formal clinical trial, there is no current role for adjuvant therapy with vascular endothelial growth factor (VEGF) pathway inhibitors in patients with resected RCC. (See "Overview of the treatment of renal cell carcinoma", section on 'Antiangiogenic and targeted therapy'.)

Immunotherapy plus targeted therapy for metastatic renal cell carcinoma (June 2017)

Checkpoint inhibitor immunotherapy targeting programmed cell death 1 (PD-1) or PD ligand 1 (PD-L1) has demonstrated improved overall survival in metastatic cancer from multiple primary sites, including second-line therapy of metastatic renal cell carcinoma (RCC). Efforts to improve further the results of checkpoint inhibition immunotherapy are looking at various combination approaches. Two phase I/II studies presented at the 2017 American Society of Clinical Oncology meeting reported promising activity for the combinations of atezolizumab plus bevacizumab and avelumab plus axitinib [37-39]. Phase III clinical trials are in progress with both of these regimens for the initial treatment of metastatic RCC. (See "Immunotherapy of renal cell carcinoma", section on 'Combined antiangiogenic plus checkpoint inhibitor therapy'.)

Oral contraceptives and ovarian cancer risk (June 2017)

Use of oral estrogen-progestin contraceptives is associated with a reduction in risk of ovarian cancer. In the largest and longest duration study of oral contraceptive use, the Royal College of General Practitioners’ Oral Contraception Study followed over 46,000 women for up to 44 years and found that ever-use of oral contraceptives was associated with a 33 percent reduction in ovarian cancer risk [40]. This finding supports previous data and our recommendation for use of oral contraceptives in women who desire ovarian cancer risk reduction who have not undergone risk reduction surgery and who are not trying to conceive. (See "Risk-reducing bilateral salpingo-oophorectomy in women at high risk of epithelial ovarian and fallopian tubal cancer" and "Epithelial carcinoma of the ovary, fallopian tube, and peritoneum: Epidemiology and risk factors", section on 'Oral contraceptives'.)

Sentinel lymph node biopsy in endometrial cancer (May 2017)

Sentinel lymph node biopsy for staging endometrial carcinoma is increasingly performed instead of selective or extended nodal dissection. In the largest multicenter prospective study of the procedure in over 300 women with clinical stage I endometrial carcinoma, successful mapping of at least one sentinel lymph node was achieved in 86 percent and the sensitivity of the sentinel lymph node was 97 percent [41]. Nevertheless, we believe further study is needed before sentinel lymph node biopsy is established as a reasonable alternative to full pelvic lymphadenectomy in endometrial carcinoma. (See "Endometrial carcinoma: Pretreatment evaluation, staging, and surgical treatment", section on 'Sentinel node biopsy'.)

Adjuvant versus early salvage radiation therapy in prostate cancer (May 2017)

The optimal management of men with pathologic T3 disease and an undetectable prostate-specific antigen (PSA) following radical prostatectomy is uncertain. There are no completed randomized trials comparing adjuvant radiation therapy (RT) with salvage RT when a biochemical relapse is first detected. A retrospective study found that observation with early salvage RT for a rising serum PSA was as effective as adjuvant RT in terms of metastasis-free and overall survival at eight years follow-up [42]. For men with pathologic T3 disease and negative or minimally positive surgical margins following radical prostatectomy and with an undetectable serum PSA, either adjuvant RT or early salvage RT (if there is a rise in serum PSA) are reasonable options. (See "Prostate cancer: Pathologic stage T3 disease or positive surgical margins following radical prostatectomy", section on 'Adjuvant RT versus early salvage RT'.)

Checkpoint inhibition immunotherapy for initial therapy of advanced urothelial carcinoma (April 2017, Modified May 2017)

The role of checkpoint inhibition immunotherapy for patients with advanced urothelial carcinoma is evolving. Pembrolizumab, an agent targeting the programmed cell death-1 (PD-1) protein, previously had been shown to prolong overall survival in patients who relapsed following chemotherapy and was approved in the United States for this indication. In an expanded phase II study of pembrolizumab as initial therapy for patients who were not candidates for cisplatin chemotherapy, the objective response rate was 29 percent and the median duration of response had not been reached [43]. Based upon these results, pembrolizumab is now approved for first-line therapy in this setting. Atezolizumab had previously been approved for this indication. (See "Treatment of metastatic urothelial cancer of the bladder and urinary tract", section on 'Immunotherapy'.)

Quality of life in men with localized prostate cancer (March 2017)

Radical prostatectomy, external beam radiation therapy, brachytherapy, and active surveillance all are important options for the treatment of low-risk, clinically localized prostate cancer. Two large prospective studies using validated instruments provide important additional insights into the impact on quality of life for each of these treatment modalities [44,45]. The choice of therapeutic approach depends upon an informed patient decision incorporating knowledge about the potential advantages and disadvantages associated with each approach along with personal preferences (table 2 and table 3 and table 4). (See "Initial approach to low- and very low-risk clinically localized prostate cancer", section on 'Quality of life'.)

Hypofractionated radiation therapy for prostate cancer (March 2017)

Historically, conventional schedules for external beam radiation therapy (RT) for localized prostate cancer have used daily doses given for seven to eight weeks. In the randomized PROFIT trial, a hypofractionated RT schedule (a larger dose per fraction given over four weeks) was noninferior in terms of both efficacy and toxicity to a conventional schedule, confirming results from three other phase III trials [46]. For patients in whom costs and convenience are important considerations, hypofractionated RT is an appropriate alternative to a conventional schedule. (See "External beam radiation therapy for localized prostate cancer", section on 'Hypofractionation'.)

Adjuvant chemotherapy for urothelial carcinoma of the upper urinary tract (January 2017)

Patients with locally advanced urothelial carcinoma of the upper urinary tract and those with positive lymph nodes following nephroureterectomy are at high risk for recurrence and death. A retrospective analysis of data from the National Cancer Database found that those receiving adjuvant chemotherapy had a significantly prolonged overall survival [47]. In the absence of randomized trials, we suggest adjuvant chemotherapy for these patients if they are fit for chemotherapy. (See "Malignancies of the renal pelvis and ureter", section on 'Adjuvant chemotherapy'.)

Chemotherapy for mediastinal nonseminomatous germ cell tumors (January 2017)

Cisplatin-based chemotherapy is the primary treatment for patients with mediastinal nonseminomatous germ cell tumors (NSGCTs). However, many patients require subsequent surgical resection of a residual thoracic mass. In a retrospective analysis, the combination of bleomycin, etoposide, and cisplatin (BEP) was associated with significantly more severe pulmonary toxicity and treatment-related deaths than the combination of etoposide, ifosfamide, and cisplatin (VIP) [48]. In the absence of randomized trials, we recommend VIP rather than BEP for the initial chemotherapy of mediastinal NSGCTs. (See "Extragonadal germ cell tumors involving the mediastinum and retroperitoneum", section on 'Systemic chemotherapy'.)

GYNECOLOGIC ONCOLOGY

Risks of breast and ovarian cancer among BRCA mutation carriers (June 2017)

In a prospective cohort study of over 9800 female BRCA mutation carriers, cumulative rates of breast and ovarian cancer until age 80 years were 72 and 44 percent for BRCA1 carriers and 69 and 17 percent for BRCA2 carriers, respectively [1]. In addition to educating women regarding their genetic risk factors, we also counsel women on how other risk modifiers, including reproductive history, use of hormonal therapy, and oophorectomy status, may impact their lifetime cancer risks. (See "Prevalence of BRCA1 and BRCA2 mutations and associated cancer risks", section on 'Breast and ovarian cancer' and "Prevalence of BRCA1 and BRCA2 mutations and associated cancer risks", section on 'Nongenetic cancer risk modifiers'.)

Laparoscopic interval debulking after neoadjuvant chemotherapy for ovarian cancer (May 2017)

Women with stage IIIC or IV ovarian cancer and unresectable disease may be candidates for neoadjuvant chemotherapy (NACT) followed by interval debulking, typically performed with laparotomy. Results of a large retrospective study suggest that laparoscopy could be a minimally invasive option for such debulking. Compared with laparotomy, laparoscopy was associated with similar three-year overall survival rates (47.5 versus 52.6 percent), similar suboptimal debulking rates (20.0 versus 22.6 percent), a shorter hospital stay by one day, and similar 30-day readmission rates [49]. Further study is needed to evaluate whether short-term morbidity is reduced with use of laparoscopy. (See "Cancer of the ovary, fallopian tube, and peritoneum: Staging and initial surgical management", section on 'Role of laparoscopy'.)

Survival with laparoscopic staging for early endometrial carcinoma (May 2017)

The second largest randomized trial of total laparoscopic hysterectomy versus total abdominal hysterectomy for treatment of apparent stage I endometrial carcinoma reported similar disease-free survival at 4.5 years and overall survival for the two techniques [50]. Based on these and previous data, laparoscopic hysterectomy appears to be a reasonable approach for initial management of women with apparent stage I endometrial cancer and may be preferable to open surgery because of lower perioperative morbidity. (See "Endometrial carcinoma: Pretreatment evaluation, staging, and surgical treatment", section on 'Laparoscopy'.)

Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer (March 2017)

In a phase III trial, enrolling approximately 550 patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who have responded to platinum-based chemotherapy, niraparib maintenance improved progression-free survival relative to placebo, although over a third experienced severe hematologic toxicity [51]. Based on these results, the US Food and Drug Administration (FDA) has approved niraparib for the maintenance treatment of such patients [52]. However, overall survival data are still immature and niraparib has not been compared with bevacizumab, which is better studied in the maintenance setting. Pending further data, we reserve use of niraparib maintenance for patients with relapsed ovarian cancer who are not candidates for bevacizumab and who are in a complete or partial response to platinum-based chemotherapy. (See "Medical treatment for relapsed epithelial ovarian, fallopian tubal, or peritoneal cancer: Platinum-sensitive disease".)

Hysterectomy-corrected cervical cancer mortality rates and racial variation (February 2017)

Cervical cancer incidence and mortality rates are known to vary across racial groups in the United States but can be underestimated if data are not adjusted for prior hysterectomy. In a population-based study that corrected for the prevalence of hysterectomy, cervical cancer mortality in black women was more than twice that of white women from 2000 to 2012 (10.1 versus 4.7 per 100,000) [53]. These data add to the body of evidence showing a racial disparity in cervical cancer mortality and support the need for research to identify and overcome the factors that account for this disparity. (See "Invasive cervical cancer: Epidemiology, risk factors, clinical manifestations, and diagnosis", section on 'Incidence and mortality'.)

MELANOMA AND OTHER SKIN CANCER

Management of a positive sentinel lymph node biopsy in patients with cutaneous melanoma (June 2017)

Historically, completion dissection of all involved nodal basins was considered the standard treatment approach for patients with cutaneous melanoma and a positive sentinel lymph node biopsy (SLNB). In the phase III Multicenter Selective Lymphadenectomy Trial II (MSLT II), patients with a positive SLNB were randomly assigned to either completion lymph node dissection or observation that included ultrasound evaluation of the appropriate lymph node basins at each follow-up visit [54]. Melanoma-specific survival at three years was the same for both groups, although the incidence of recurrence in regional lymph nodes was higher in patients managed with observation and ultrasound surveillance. The incidence of lymphedema was higher in patients who underwent immediate lymph node dissection. For patients with a positive SLNB, we suggest clinical observation coupled with ultrasound surveillance of the positive nodal basin. Completion lymph node dissection is indicated if, in the absence of distant metastases, there is evidence of regional lymph node recurrence. (See "Evaluation and treatment of regional lymph nodes in melanoma", section on 'Multicenter Selective Lymphadenectomy Trial II'.)

Adjuvant ipilimumab in stage III melanoma (June 2017)

Ipilimumab is approved at a dose of 10 mg/kg as adjuvant therapy for stage III melanoma based on prolongation of overall survival. An unplanned exploratory analysis of the E-1609 trial was presented at the 2017 American Society of Clinical Oncology meeting comparing the 10 mg/kg versus 3 mg/kg dosage schedule of ipilimumab in the adjuvant setting [55]. Toxicity was significantly decreased with the 3 mg/kg schedule and there was no difference in the three-year relapse-free survival rate. While stronger evidence supports the use of the 10 mg/kg dose, there are currently inadequate data to require the selection of this dose over the 3 mg/kg dose in the adjuvant setting. (See "Adjuvant immunotherapy for melanoma", section on 'Efficacy and toxicity'.)

Durability of pembrolizumab-induced remissions for advanced melanoma (June 2017)

In the previously reported phase III KEYNOTE-006 trial, pembrolizumab was compared with ipilimumab, with treatment continuing for up to two years in the absence of progression or toxicity. Results were updated at the 2017 American Society of Clinical Oncology meeting [56]. Overall, 19 percent of responding patients completed the two years of planned treatment with pembrolizumab and discontinued therapy. With a median follow-up of 9.7 months after pembrolizumab discontinuation, 91 percent of patients remained progression free. These results provide additional support for the durability of responses to pembrolizumab and the ability to discontinue treatment after two years. (See "Immunotherapy of advanced melanoma with immune checkpoint inhibition", section on 'Anti-PD-1 versus anti-CTLA-4 antibodies'.)

Avelumab immunotherapy for metastatic Merkel cell carcinoma (March 2017)

Chemotherapy historically has been used to treat advanced Merkel cell carcinoma (MCC), although it has not been shown to prolong survival and has been associated with significant toxicity. Avelumab, a monoclonal antibody that blocks the PD-1 ligand (PD-L1), was approved by the US Food and Drug Administration based on a phase II study in patients who had received prior chemotherapy demonstrating a 32 percent response rate (23 percent partial and 9 percent complete), relatively durable remissions (six-month progression-free survival 40 percent), and a favorable side effect profile [57,58]. Based upon these results, avelumab is our preferred treatment for the initial treatment of patients with metastatic MCC. (See "Staging and treatment of Merkel cell carcinoma", section on 'Avelumab'.)

Targeted therapy for advanced melanoma with an NRAS mutation (March 2017)

Binimetinib, an inhibitor of MEK, is able to block the MAPK pathway in patients with advanced melanoma and an NRAS driver mutation. In a phase III trial in this patient population, binimetinib significantly prolonged progression-free survival compared with chemotherapy in patients who had progressed during or after immunotherapy [59]. Binimetinib is not currently approved for use outside of a clinical trial setting. (See "Molecularly targeted therapy for metastatic melanoma", section on 'NRAS-mutated tumors'.)

Retreatment with BRAF and MEK inhibition in advanced melanoma (March 2017)

Targeted therapy with a combination of BRAF and MEK inhibition is an important treatment option for tumors that contain a driver mutation in BRAF. However, most patients eventually develop progressive disease. Results from a prospective phase II study provide evidence that retreatment with the combination of a BRAF and MEK inhibitor may be of value in patients who have acquired resistance to both mitogen-activated protein kinase (MAPK)-targeted therapy and immune checkpoint inhibitors [60]. (See "Molecularly targeted therapy for metastatic melanoma", section on 'Retreatment'.)

NEUROONCOLOGY

Postoperative stereotactic radiosurgery for resected brain metastases (July 2017)

Two randomized trials lend further support to the use of postoperative stereotactic radiosurgery (SRS) rather than whole brain radiation therapy (WBRT) or observation after resection of a single brain metastasis. In one trial, patients treated with single-fraction SRS to the surgical cavity had improved neurocognitive function and similar overall survival compared with those treated with WBRT [61]. In the second trial, single-fraction SRS decreased rates of local recurrence compared with observation, especially for tumors smaller than 2.5 cm preoperatively [62]. Larger tumors may be better suited for multiple-fraction SRS, which allows for a higher dose of radiation to be delivered to the surgical cavity. (See "Overview of the treatment of brain metastases", section on 'Postoperative radiation'.)

PALLIATIVE AND SUPPORTIVE CARE

Safe storage of prescription opioids (May 2017)

Although safe storage of prescription opioid medications (eg, locked cabinet) is recommended, it infrequently occurs. In a United States nationally representative survey of over 1000 adults with prescription opioid use in the past 12 months, only 9 percent reported safe storage of their medications [63]. In further analysis of those adults with children younger than 18 years of age in the household, safe storage was reported in less than one-third of households with young children and 12 percent of households with children older than six years of age [64]. These results support the need for anticipatory guidance by health care providers, emphasizing opioid safe storage and how it may limit opioid misuse and overdose, especially in households with children and adolescents. Further research should focus on developing and implementing effective means of secure storage in households. (See "Opioid intoxication in children and adolescents", section on 'Safe storage'.)

US REMS requirements eliminated for use of epoetin and darbepoetin (April 2017)

The US Food and Drug Administration (FDA) instituted a Risk Evaluation and Mitigation Strategy (REMS) program in 2010 for the use of erythropoiesis stimulating agents (ESAs) in patients receiving myelosuppressive chemotherapy for cancer, which required hospitals and physicians to enroll, complete training, and provide written documentation of the discussion of risk with patients prior to instituting ESAs. In 2017, the FDA determined that full implementation of the REMS had had minimal impact on ESA utilization beyond the changes observed after the Medicare restriction of coverage for ESAs and multiple other FDA regulatory actions. The FDA concluded that the REMS was no longer necessary and the REMS requirements were eliminated for these ESA products in patients receiving myelosuppressive chemotherapy for cancer [65]. (See "Role of erythropoiesis-stimulating agents in the treatment of anemia in patients with cancer", section on 'APPRISE: the FDA Risk Evaluation and Mitigation Strategy program'.)

Concurrent benzodiazepines in opioid-using patients and overdose risk (April 2017)

Benzodiazepines can potentiate the respiratory depressant effects of opioid medication, and concurrent use may be a factor in the rising rate of opioid overdose. In an analysis of a large sample of patients prescribed an opioid, the proportion who concurrently received a benzodiazepine nearly doubled over 12 years [66]. Concurrent use of both medications was associated with an increased risk of opioid overdose compared with patients receiving only the opioid. Avoiding this medication combination may prevent some overdoses. (See "Prevention of lethal opioid overdose in the community", section on 'Risk factors'.)

Naldemedine for opioid-induced constipation (March 2017)

The benefit of naldemedine, an oral peripherally acting opioid receptor antagonist, for opioid-induced constipation (OIC) was shown in two identically designed 12-week phase III randomized trials conducted in patients with noncancer chronic pain and OIC [67]. In a preliminary report, naldemedine, compared with placebo, decreased constipation and was well tolerated with no signs or symptoms of opioid withdrawal or decrease in opioid analgesic efficacy. Naldemedine has been approved in the United States for OIC in adult patients with chronic noncancer pain [68]. However, efficacy has also been shown for treatment of OIC in cancer patients [69], and naldemedine can be used off label in this population. The European Medicines Agency has approved naldemedine for treatment of OIC without restriction to noncancer pain [70]. (See "Cancer pain management with opioids: Prevention and management of side effects", section on 'Other oral agents'.)

Scalp hypothermia to prevent chemotherapy-induced alopecia (March 2017)

Two prospective studies have evaluated the efficacy of two different automated scalp cooling devices in women with early stage breast cancer [71,72]:

In an interim analysis of a randomized trial comparing the Paxman Scalp Cooling device and no scalp hypothermia for women with breast cancer receiving adjuvant chemotherapy (one-third anthracycline-based, the remainder taxane-based), one-half of the hypothermia group had limited hair loss (to less than 50 percent, not requiring a wig) compared with none in the control group [71]. Adverse events were all grade 1 and 2, including primarily headache and feeling cold. The success rate was higher with taxane-containing regimens.

In a multicenter prospective cohort study, 101 patients receiving non-anthracycline taxane-based chemotherapy and who used the DigniCap Scalp Cooling device were compared with 16 concurrently treated controls who did not use the device [72]. Two-thirds of the intervention group, compared with none of the control group, had limited hair loss (to less than 50 percent) one month after the end of chemotherapy. At a median follow-up of 2.5 years, no patient developed scalp metastases.

These results confirm prior studies on the efficacy and safety of scalp hypothermia to reduce chemotherapy-related hair loss. The FDA approved one device (DigniCap) for patients with breast cancer in December 2015 and expanded the approval to cover all solid tumors in July 2017. (See "Chemotherapy-induced alopecia", section on 'Efficacy and safety'.)

Early initiation of palliative care and survival (February 2017)

When initiated early in the disease course, palliative care improves clinical and quality of care outcomes; randomized trials in patients with cancer or advanced lung disease also report a survival advantage, although more diverse palliative care populations have not been studied. A meta-analysis of seven randomized trials involving 2184 patients concluded that there was no association between early initiation of palliative care and overall survival [73]. Previous reports of a possible survival advantage may have reflected bias in patient selection; only one of the seven trials was rated as having a low risk of bias. (See "Benefits, services, and models of subspecialty palliative care", section on 'Rationale for palliative care'.)

Palliative care during hematopoietic cell transplantation (February 2017)

For patients with serious life-threatening illness, comprehensive palliative care can be successfully integrated with disease-modifying treatment. The benefits of delivering palliative care alongside potentially curative treatment were shown in a randomized trial of inpatient palliative care consultation versus usual transplant care in 160 adults with hematologic malignancies undergoing autologous or allogeneic hematopoietic cell transplantation [74]. At two weeks posttransplant, the increase in depression, anxiety, and overall symptom burden was less in the intervention group, and the decrease in quality of life (QOL) was also smaller. Depression and QOL benefits persisted at three months. (See "Benefits, services, and models of subspecialty palliative care", section on 'Rationale for palliative care'.)

Antipsychotics for delirium in terminally ill patients (January 2017)

The benefit of antipsychotics for management of delirium in terminally ill patients has been called into question by a randomized trial in which 247 inpatients of a hospice or palliative care service with mild to moderately severe delirium were assigned to oral risperidone, haloperidol, or placebo every 12 hours for 72 hours [75]. All patients received individualized supportive care. Patients who received antipsychotics had more severe delirium, worse delirium-associated distress scores, more use of midazolam, more extrapyramidal effects, and worse short-term survival. In our view, this study does not justify abandoning the use of antipsychotics for severely agitated delirious patients but points to the importance of reversing precipitating causes, providing best supportive care for symptomatic distress associated with delirium, and the need for additional research on the use of antipsychotics. (See "Overview of managing common non-pain symptoms in palliative care", section on 'Treatment'.)

Dosing interval for zoledronic acid in patients with bone metastases (January 2017)

For patients with bone metastases from a solid tumor, the approved dose and schedule of administration for zoledronic acid to reduce the frequency of skeletal-related events (SREs) is 4 mg every three to four weeks. Less frequent dosing is supported by data from CALGB (Alliance) trial 70604, which randomly assigned 1822 patients with bone metastases from breast or prostate cancer or multiple myeloma to the same dose of zoledronic acid every 4 or every 12 weeks for two years, starting with the first dose. There was no difference in the proportion of patients who developed at least one SRE (29.5 versus 28.6 percent) [76]. There are now sufficient data in breast and castration-resistant prostate cancer to support dosing of zoledronic acid every 12 rather than every 4 weeks, and we suggest this approach for most patients. We still prefer every-four-week dosing, at least initially, for patients who have extensive or highly symptomatic bone metastases. (See "Osteoclast inhibitors for patients with bone metastases from breast, prostate, and other solid tumors", section on 'Dosing interval'.)

THORACIC ONCOLOGY

Revised follow-up for a solitary pulmonary nodule (June 2017)

Fleischner Society guidelines have been updated to reflect the accumulating data on the malignancy risk of incidental pulmonary nodules and growth rates of lung cancer [77]. Important changes include guidance on identifying benign nodules with minimal follow-up imaging. For patients with a solid or subsolid (ground glass or part-solid) solitary pulmonary nodule measuring <6 mm, follow-up computed tomography (CT) is optional, but no longer required. A solitary pulmonary nodule that is solid and unchanged on serial CT over a two-year period, or subsolid and unchanged over a five-year period, is likely benign and does not need further diagnostic evaluation. Recommendations in UpToDate have been revised to reflect these new guidelines. (See "Diagnostic evaluation and management of the solitary pulmonary nodule", section on 'Management strategy' and "Diagnostic evaluation and management of the solitary pulmonary nodule", section on 'Solid nodules ≤8 mm'.)

No benefit with nivolumab as frontline treatment for advanced NSCLC (June 2017)

Immunotherapy using programmed death receptor 1 (PD-1) antibodies is an area of active investigation in non-small cell lung cancer (NSCLC). In a phase III trial of over 400 treatment-naïve NSCLC patients with at least 5 percent programmed death receptor-ligand 1 (PD-L1) expression, nivolumab did not improve progression-free or overall survival compared with platinum-doublet chemotherapy [78]. Further research is needed to identify patients who might benefit from frontline nivolumab. (See "Immunotherapy of non-small cell lung cancer with immune checkpoint inhibition", section on 'First-line setting'.)

Adjuvant EGFR inhibition in EGFR-mutated NSCLC (June 2017)

Chemotherapy has been used as standard adjuvant systemic treatment for non-small cell lung cancer (NSCLC), regardless of the presence of a driver mutation. However, in preliminary results of a phase III trial of over 200 patients with stage II to IIIA epidermal growth factor receptor (EGFR)-mutated NSCLC, median disease-free survival was longer (20 versus 18 months) and severe adverse events were less frequent for those randomly assigned to 24 months of adjuvant gefitinib compared with those assigned to chemotherapy [79]. We await overall survival data before routine incorporation of adjuvant EGFR inhibition into clinical practice. (See "Adjuvant systemic therapy in resectable non-small cell lung cancer", section on 'Molecularly targeted agents'.)

Next-generation ALK-inhibitors in crizotinib-naive ALK-positive NSCLC (June 2017)

For patients with advanced anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC), crizotinib has been administered as frontline therapy. However, newer agents have shown promising efficacy in advanced ALK-positive NSCLC:

In a global trial of 303 patients randomly assigned to frontline crizotinib versus the next-generation inhibitor alectinib (ALEX), those receiving alectinib experienced a longer progression-free survival (PFS, not reached versus 11.1 months), with fewer toxicities, at a median follow-up of approximately 18 months [80]. These results are consistent with an earlier Japanese trial [81].

In a phase III trial of 376 patients comparing ceritinib, another next-generation ALK inhibitor, with pemetrexed and a platinum agent, ceritinib improved progression-free survival (17 versus 8 months) [82]. Ceritinib has not been compared with crizotinib in the frontline setting.

For patients with newly diagnosed, ALK-positive NSCLC, we now recommend frontline therapy with alectinib. For those without access to alectinib, appropriate alternatives include crizotinib or ceritinib. (See "Anaplastic lymphoma kinase (ALK) fusion oncogene positive non-small cell lung cancer".)

Brigatinib in crizotinib-refractory ALK-positive NSCLC (May 2017)

While the first generation anaplastic lymphoma kinase (ALK) inhibitor crizotinib is highly active in patients with ALK-positive non-small cell lung cancer (NSCLC), almost all patients develop resistance to the drug. In a phase II study of 222 patients with crizotinib-refractory, ALK-positive NSCLC receiving the next generation ALK inhibitor brigatinib, progression-free survival was 9.2 and 12.9 months, respectively, among those receiving a lower and higher dose of the agent [83]. Although it has been associated with early pulmonary toxicity in approximately 9 percent of cases, brigatinib is now approved by the US Food and Drug Administration (FDA) for patients with ALK-positive metastatic NSCLC who have progressed on or are intolerant to crizotinib [84]. We consider brigatinib or another next generation ALK inhibitor, ceritinib or alectinib, to be appropriate therapy in this setting. (See "Anaplastic lymphoma kinase (ALK) fusion oncogene positive non-small cell lung cancer", section on 'Brigatinib'.)

No added benefit from MEK inhibitor in KRAS-mutant NSCLC (May 2017)

Although KRAS-mutant lung cancer is the largest genomically defined subset of non-small cell lung cancer (NSCLC), there are no established targeted therapies for its treatment. In a phase III trial of over 500 patients with advanced KRAS-mutant NSCLC, the addition of selumetinib, a mitogen-activated protein kinase (MEK) inhibitor, to docetaxel failed to improve progression-free survival, overall survival, or response rate relative to docetaxel alone [85]. We continue to treat patients with advanced KRAS-mutant NSCLC in the same manner as those with unknown or untargetable mutation status. (See "Personalized, genotype-directed therapy for advanced non-small cell lung cancer", section on 'Targeted therapy under investigation'.)

Pembrolizumab approved with chemotherapy in treatment-naïve nonsquamous NSCLC (May 2017)

The anti-programmed death-1 (PD-1) antibody pembrolizumab has been approved by the US Food and Drug Administration (FDA) in combination with carboplatin and pemetrexed for treatment-naïve patients with advanced, nonsquamous non-small cell lung cancer (NSCLC). In a randomized phase II trial of 123 such patients, the addition of pembrolizumab to carboplatin and pemetrexed improved objective response rate (55 versus 29 percent, respectively) and progression-free survival (13 versus 6 months, respectively) relative to chemotherapy alone [86]. Although we continue to prefer pembrolizumab monotherapy for those with ≥50 percent tumor cell staining for PD-L1, and targeted agents for those with EGFR or ALK genetic alterations, we now offer the combination of carboplatin, pemetrexed, and pembrolizumab as one frontline treatment option for other patients with nonsquamous NSCLC. (See "Immunotherapy of non-small cell lung cancer with immune checkpoint inhibition", section on 'Pembrolizumab'.)

OTHER ONCOLOGY

Proton pump inhibitors may decrease absorption of capecitabine (July 2017)

Elevated gastric pH levels associated with use of proton pump inhibitors may alter dissolution and absorption of capecitabine and impair its efficacy. A secondary analysis of a large phase III study comparing capecitabine plus oxaliplatin with or without lapatinib for the treatment of advanced gastroesophageal cancer showed lower overall survival in patients who received concomitant proton pump inhibitors; a similar finding has been reported in patients receiving adjuvant capecitabine for colon cancer [87]. Patients who are receiving a capecitabine-containing regimen for any cancer should probably not take proton pump inhibitors concurrently. (See "Systemic therapy for locally advanced unresectable and metastatic esophageal and gastric cancer", section on 'Oral fluoropyrimidines' and "Adjuvant therapy for resected stage III (node-positive) colon cancer", section on 'Capecitabine'.)

Types of cancers associated with obesity (April 2017)

Excess weight is associated with an increased risk of developing and dying from cancer, but the number and types of cancers are inconsistent across studies. In a review of 204 meta-analyses that investigated the association between indices of adiposity and developing 36 primary cancers and their subtypes, associations were identified for esophageal adenocarcinoma, multiple myeloma, and cancers of the gastric cardia, colon, rectum, biliary tract, pancreas, breast (in women who had never taken hormones), endometrium, ovary, and kidney [88]. (See "Obesity in adults: Health consequences", section on 'Cancer'.)

Decline in secondary malignancies among childhood cancer survivors (March 2017)

In addition to recurrences of primary malignancies, cancer survivors are at a higher risk for secondary malignancies as a result of their cancer treatments. In a study of over 23,000 survivors of childhood cancer, 6.9 percent of survivors experienced neoplasms, most commonly breast or thyroid cancer, over a mean follow-up of 20.5 years [89]. The frequency of subsequent malignancies decreased by decade of diagnosis (2.1, 1.7 and 1.3 percent for the 1970s, 1980s and 1990s, respectively). This decline may be related to a decrease in the proportion of individuals receiving radiation and the median radiation dose administered over time. (See "Overview of cancer survivorship care for primary care and oncology providers".)

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