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Initial treatment with either neoadjuvant chemoradiation (CRT) or induction FOLFOX (5-Fluorouracil, leucovorin, and oxaliplatin) chemotherapy followed by CRT is considered standard treatment for locally advanced rectal cancer. We compared patient-reported outcomes (PRO) during CRT in patients who had received induction chemotherapy versus those who did not.We reviewed records of patients with locally advanced rectal cancer who were treated with CRT between September 2009 and October 2014, and who had completed ≥ 4 PRO assessments during treatment. Clinician- and patient-reported toxicities were collected each week during treatment. We fit binomial generalized linear models to maximum toxicity scores across all patients' visits.Of 123 patients with ≥ 4 PRO assessments, 87 (71%) patients reported a clinically meaningful PRO score of 3 or higher for diarrhea, and 91 (74%) patients reported a PRO score of ≥ 3 for urgency, during 1 or more weeks of treatment, corresponding to 'very frequent' or worse. Of 116 patients who had also completed ≥ 4 clinician-reported assessments for descriptive analysis, clinically significant diarrhea (Common Terminology Criteria for Adverse Events grade ≥ 2) was reported in 9% of patients, and grade 2 proctitis and cystitis were reported in 20% and 4%, respectively. Eighty-four (68%) patients had undergone induction chemotherapy prior to CRT. Patients who received induction chemotherapy had 68% lower odds of experiencing significant urgency (odds ratio [OR], 0.32; 95% confidence interval [CI], 0.11-0.95; P = .04), 76% lower odds of bleeding (OR, 0.24; 95% CI, 0.1-0.62; P .01), and 75% lower odds of tenesmus (OR, 0.25; 95% CI, 0.11-0.6; P .01) versus those treated with upfront CRT.Based on PROs, a high proportion of patients experienced clinically significant symptoms during pelvic CRT, with diarrhea and urgency being most commonly reported. This appears to be under-reported on clinician-reported assessments. Delivery of induction chemotherapy was associated with lower odds of experiencing urgency, bleeding, and tenesmus on PROs during subsequent CRT, with no significant impact on diarrhea and rectal pain.

Background Treatment of advanced anal squamous cell cancer (SCC) is usually with the combination of cisplatin and 5-fluorouracil, which is associated with heterogeneous responses across patients and significant toxicity. We examined the safety and efficacy of a modified schedule, FOLFCIS (leucovorin, fluorouracil, and cisplatin), and performed an integrated clinical and genomic analysis of anal SCC. Patients and Methods We reviewed all patients with advanced anal SCC receiving first-line FOLFCIS chemotherapy – essentially a FOLFOX (leucovorin, fluorouracil, and oxaliplatin) schedule with cisplatin substituted for oxaliplatin – in our institution between 2007 and 2017, and performed deep sequencing to identify genomic markers of response and key genomic drivers. Results Fifty-three patients with advanced anal SCC (48 metastatic; 5 unresectable, locally advanced) received first-line FOLFCIS during this period; all were platinum-naive. The response rate was 48% (95% confidence interval [CI], 32.6%-63%). With a median follow-up of 41.6 months, progression-free survival and overall survival were 7.1 months (95% CI, 4.4-8.6 months) and 22.1 months (95% CI, 16.9-28.1 months), respectively. Among all patients with advanced anal SCC that underwent sequencing during the study period, the most frequent genomic alterations consisted of chromosome 3q amplification (51%) and mutations in PIK3CA (29%) and KMT2D (22%). No genomic alteration correlated with response to platinum-containing treatment. Although there were few cases, patients with human papillomavirus-negative anal SCC did not appear to benefit from FOLFCIS, and all harbored distinct genomic profiles with TP53, TERT promoter, and CDKN2A mutations. Conclusions FOLFCIS appears effective and safe as first-line chemotherapy in patients with advanced anal SCC and represents an alternative treatment option for these patients.

Thermal ablation of colorectal cancer liver metastases with minimum margin > 10 mm offers the best local tumor control. Biliary complications occurred only in patients that received hepatic artery infusion especially in the face of pre-existing biliary dilatation, exposure to bevacizumab, and ablation with minimum margin > 10 mm. For patients at risk, such as those in the hepatic artery infusion group, a margin of 6 to 10 mm offers 76% local tumor control rate and 4% major biliary complications incidence.Introduction: The purpose of this study was to identify risk factors associated with local tumor progression-free survival (LTPFS) and complications after colorectal liver metastases (CLM) thermal ablation (TA). Patients and Methods: This retrospective analysis included 286 patients with 415 CLM undergoing TA (radiofrequency and microwave ablation) in 378 procedures from January 2003 to July 2017. Prior hepatic artery infusion (HAI), bevacizumab, pre-existing biliary dilatation, ablation modality, minimal ablation margin (MM), prior hepatectomy, CLM number, and size were analyzed as factors influencing complications and LTPFS. Statistical analysis included the Kaplan-Meier method, Cox proportional hazards model, competing risk analysis, univariate/multivariate logistic/exact logistic regressions, and the Fisher exact test. Complications were reported according to modified Society of Interventional Radiology guidelines. Results: The median follow-up was 31 months. There was no LTP for MM > 10 mm. Smaller tumor size, increased MM, and prior hepatectomy correlated with longer LTPFS. The major complications occurred following 28 (7%) of 378 procedures. There were no biliary complications in HAI-naive patients, versus 11% in HAI patients (P 10 mm. In HAI patients, ablation with 6 to 10 mm and > 10 mm MM resulted in major biliary complication rates of 4% and 21% (P = .0011), with corresponding LTP rates of 24% and 0% (P = .0033). In HAI-naive patients, the LTP rates for 6 to 10 mm and > 10 mm MM were 27% and 0%, respectively. Conclusions: No LTP was seen for MM > 10 mm. Biliary complications occurred only in HAI patients, especially in those with biliary dilatation, bevacizumab, and MM > 10 mm. In HAI patients, MM of 6 to 10 mm resulted in 76% local tumor control and 4% major biliary complications incidence. (C) 2020 Published by Elsevier Inc.

Colorectal cancer (CRC) is the second leading cause of cancer-related death in the United States. Advances in therapies over the past decade have led to improved outcomes for many patients. In addition to cytotoxic chemotherapy, advances in our understanding of tumor biology have led to the development of agents targeted against molecular pathways. The addition of these so-called targeted agents has been shown to add further to the activity of chemotherapy combinations and, in some cases, to offer modest survival advantages. However, these agents are not without substantial potential for toxicity. This review will discuss the available therapies and the data to justify the appropriate use and nonuse of targeted therapies in patients with metastatic CRC.

Background Heat shock protein 90 (Hsp90) is a cellular chaperone that is required for the maturation and stability of a variety of proteins that play key roles in colon cancer initiation and progression. The primary objective of the current study was to define the safety and efficacy of ganetespib, a novel, selective small-molecule Hsp90 inhibitor, in patients with refractory metastatic colorectal cancer. Patients and Methods The study was a single-arm, Simon 2-stage, phase II trial for patients with chemotherapy-refractory, metastatic colorectal cancer. Patients received ganetespib 200 mg/m 2 intravenously. Tumor tissue was collected before treatment and 48 hours after treatment for changes in expression of Hsp90 client proteins and other potential pharmacodynamics markers. V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS), v-Raf murine sarcoma viral oncogene homolog B, and phosphatidylinositol-4, 5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) mutational status was also determined. Results Seventeen patients were treated (median age, 58; range, 44-79 years). No patients demonstrated objective regression of disease. Two patients had stable disease of 6.8 and 5.1 months duration. Serious adverse events that were potentially attributable to ganetespib included diarrhea (12%, n = 2), fatigue (17%, n = 3), and increased aspartate aminotransferase/alanine aminotransferase (12%, n = 2) and alkaline phosphatase (6%, n = 1) levels. Of the 17 evaluable patients, 9 (53%) including patients with stable disease as best response, had KRAS-mutant tumors. Conclusion In this first phase II investigation of an Hsp90 inhibitor in colorectal cancer, ganetespib as a single agent did not demonstrate activity in chemotherapy-refractory metastatic colorectal cancer. However, on the basis of the drug's promising preclinical combination data and the relatively mild toxicity profile, further clinical investigation of this agent in combination with standard cytotoxic agents is planned.

Background Studies indicate that the incidence of young women diagnosed with colorectal cancer is rising, thus there is an increasing number of female colorectal cancer survivors of premenopausal and child-bearing age. Adjuvant FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin) chemotherapy is the most widely used standard treatment for stage III and high-risk stage II colon cancer. We evaluated the incidence of FOLFOX-induced amenorrhea in women age 50 and younger treated with adjuvant therapy for colorectal cancer. Patients and Methods A search of pharmacy records identified 119 women age 50 or younger who received adjuvant FOLFOX chemotherapy at Memorial Sloan-Kettering for stage II or III colorectal cancer from January 2002 and January 2011. Eligible patients were mailed an anonymous questionnaire. The returned surveys were reviewed and the results tallied. Results Seventy-three patients returned the questionnaire. Twenty-four patients were excluded from analysis: 19 were treated with pelvic radiotherapy, 2 patients had undergone bilateral oophorectomy, 2 had a hysterectomy, and 1 stopped menstruating before diagnosis. Forty-nine patient responses were analyzed. In total, 41% (n = 20) experienced amenorrhea during chemotherapy. Sixteen percent had persistent amenorrhea 1 year after completion of chemotherapy. The incidence of amenorrhea during chemotherapy trended higher in patients aged older than 40 compared with patients aged 40 and younger (59% vs. 31% [P = .075]). There was no statistically significant difference in persistent amenorrhea between the 2 age groups (24% vs. 13%; P = .42). Conclusion In this retrospective series, there appears to be a trend toward FOLFOX induced amenorrhea during chemotherapy increasing with age. Twenty-four percent of women older than the age of 40 were found to have persistent amenorrhea after FOLFOX therapy. Because of the small sample size, the study is underpowered to detect a statistically significant difference between older and younger patients. Prospective studies are planned to further characterize the effect of FOLFOX on early menopause and fertility.