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Background: Despite contributions provided by the recent clinical trials, several issues and challenges still remain unsolved in adjuvant colon cancer (CC). Hence, further studies should be planned to better refine risk assessment as well as to establish the optimal treatment strategy in the adjuvant setting. However, it is necessary to request adequate, contemporary and relevant variables and report them homogeneously in order to bring maximal information when analyzing their prognostic value., Material and Methods: The project was devised to gain a consensus from experts engaged in the planning, accrual and analyses of stage II and III CC clinical trials, to identify mandatory and recommended baseline variables in order to i) harmonize future data collection worldwide in clinical trials dedicated to adjuvant treatment of CC; ii) propose guidance for Case Report Forms to be used for clinical trials in this setting. A total of 72 questions related to variables that should be reported and how to report them in adjuvant clinical trials were approved and then voted to reach a final consensus from panelists., Results: Data items on patient-related factors, histopathological features, molecular profile, circulating biomarkers and blood analyses were analyzed and discussed by the whole expert panel. For each item, we report data supporting the acquired consensus and the relevant issues that were discussed. Nineteen items were deemed to be mandatory for resected stage III patients and 24 for resected stage II disease. In addition, 9 and 4 items were judged as recommended for stage III and II, respectively., Conclusion: In our opinion, these 28 variables should be used and uniformly reported in more comprehensive CRFs as research groups design future clinical trials in the field of adjuvant colon cancer., Competing Interests: Declaration of Competing Interest All authors declare no competing interest regarding this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: National and international guidelines recommend the use of 1 dose of intravesical chemotherapy immediately following surgery for nonmuscle invasive bladder cancer, which is performed infrequently on a population level. We sought to understand the importance of potential environmental and clinical dimensions involved in the decision to offer this therapy., Materials and Methods: Urologists from the Michigan Urological Surgery Improvement Collaborative (MUSIC) rated 8 distinct clinical vignettes involving patients with nonmuscle invasive bladder cancer. A ratings-based conjoint analysis method was used to evaluate the clinical vignette responses. Each vignette included 4 clinical dimensions and 2 environmental dimensions, with each dimension consisting of 2 possible attributes. The relative importance of each attribute was derived from the regression model and ranked in order., Results: A total of 58 urologists answered the clinical vignettes which represents >75% of MUSIC sites. The median age of urologists was 53, most were male, and median years in practice was 20 years post residency. An environmental attribute, having a recovery room protocol for instilling and disposing of the chemotherapy, ranked as the most influential attribute for giving postoperative chemotherapy (utility=8.6). The clinical attribute yielding the strongest preference for giving chemotherapy was tumor grade (utility=4.9). These preferences varied by different subgroups of urologists, particularly regarding the type of practice a urologist was in., Conclusions: This study demonstrates that urologists have clear preferences for when they offer postoperative immediate chemotherapy. Factors beyond just clinical variables play a role in this decision making process such as the structure of the recovery room.

Abstract: Induction chemotherapy (IC) and adjuvant chemotherapy (AC) are used to enhance tumor locoregional control and support early treatment for distant metastases. However, optimum combinatorial treatment of these chemoradiotherapy regimens with radiotherapy in curing locoregionally advanced nasopharyngeal carcinoma (NPC) remains unclear. Here, we evaluate the efficacy and therapeutic outcome of a combinatorial treatment strategy involving IC, intensity-modulated radiotherapy (IMRT), and AC, by retrospectively analyzing 243 NPC patients who were treated by IC followed by IMRT and AC. The rates of 3-/5-year local-regional control rate, distant failure-free rate (DFFR), progression-free survival (PFS), and overall survival (OS) were 93.3%/90.3%, 84.2%/79.4%, 79.6%/74.4%, and 84.0%/72.6%, respectively. The 3-/5-year OS rates of patients in stage III or IVA were 91.5%/75.1% and 86.5%/56.5%, respectively. Combination cisplatin with paclitaxel showed no significance in OS as compared to cisplatin plus 5-fluorouracil (P-value = .17). Total four-cycle IC and AC was significantly beneficious versus three-cycle in DFFR (P-value = .04), as well as total 6 chemotherapy cycles compared to 4 in DFFR and PFS (P-value = .03 and P-value = .01, respectively). All survival indicators were adversely affected by T-category, while N-category could only predict DFFR and PFS. Radiation dosage represented as a second prognostic factor for local control. We propose that IC combined with IMRT and AC for locoregionally advanced NPC shows effective treatment outcomes., Competing Interests: The authors declare that they have no potential conflict of interest relevant to this article., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Aim: To describe real-world breast cancer medications among reproductive-age women. Patients & methods: Using data from a Japanese claims database, anticancer prescriptions were classified into seven categories of amenorrhea risk based on fertility preservation guidelines. Results: We identified 2999 women with records of breast cancer and anticancer prescription from 2005 to 2018. The proportions of prescriptions were as follows: high, 4.1-12.9%; intermediate: 6.0-16.3%; low: 0.4-2.3%; very low/no: 0.3-12.2%; unknown: 33.9-45.5%; unlisted combination: 12.2-23.4%; and unlisted drug: 12.5-26.7%. The common drugs in the unknown category were trastuzumab (n = 1527), docetaxel (n = 1014), and paclitaxel (n = 995). For medications unlisted in the guidelines, various drugs and drug combinations were observed. Conclusion: Numerous anticancer drugs are currently being prescribed with insufficient evidence regarding amenorrhea risk.

Background: Previous studies of stage III colon cancer using the hazard function demonstrated that the risk of recurrence in patients with adjuvant chemotherapy never exceeded that of patients without adjuvant chemotherapy. However, it is unclear whether the same can be said for rectal cancer patients and whether adjuvant chemotherapy reduces recurrence. This study aimed to compare the recurrence hazard of stage III rectal cancer with that of colon cancer by adjuvant chemotherapy status using the hazard function, a method that allows for the assessment of instantaneous risk of recurrence over time., Methods: This retrospective nationwide study consisted of 10,356 patients with stage III colorectal cancer who underwent curative resection between January 1997 and December 2012 in Japan. Recurrence hazards of rectal and colon cancers were compared between patients treated with adjuvant chemotherapy and those who were not. Analyses in which recurrence was divided into local and distant recurrence were also performed., Results: The hazard rate of recurrence in rectal cancer patients with adjuvant chemotherapy was consistently lower throughout the follow-up period, and the peak time of recurrence later, compared to patients without adjuvant chemotherapy (peaked at 15.7 vs. 7.1 months). Adjuvant chemotherapy also strongly suppressed distant recurrence but not local recurrence in rectal cancer patients. Similar results were observed in colon cancer patients., Conclusions: Our results using nationwide real-world data in Japan suggest that, similar to what is observed in colon cancer patients, adjuvant chemotherapy delays the peak of recurrence and suppresses distant recurrence in stage III rectal cancer patients.

Background: In 2004, the European Study Group for Pancreatic Cancer (ESPAC)-1 long-term data concluded that adjuvant chemotherapy provided a survival benefit for patients with pancreatic ductal adenocarcinoma (PDAC), whereas adjuvant chemoradiation was associated with worse overall survival. In this study, we investigated how long it took for US practice patterns to change following this trial., Methods: The National Cancer Database was used to identify patients with stage I-III PDAC who underwent R0 or R1 resection followed by adjuvant chemotherapy or chemoradiation between 1998 and 2015. A multivariate analysis was performed to determine predictors of receiving adjuvant chemoradiation in the post-ESPAC-1 era., Results: Between 1998 and 2015, adjuvant chemotherapy use increased from 2.9% to 51.6%, whereas adjuvant chemoradiation decreased from 49.5% to 22.9%. In 2010, adjuvant chemotherapy utilization surpassed that of chemoradiation. For patients diagnosed in the post-ESPAC-1 era, adjuvant chemotherapy (n = 7733) and chemoradiation (n = 6969) groups were compared. Patients who underwent adjuvant chemoradiation were younger, had private insurance, underwent surgery at nonacademic centers, and had more pathologically advanced cancers (all P < 0.01). After 2010, R1 resection was the strongest independent predictor of adjuvant chemoradiation use by multivariate analysis (OR 2.05, CI 1.8-2.3, P < 0.01)., Conclusions: Adjuvant chemotherapy use exceeded that of adjuvant chemoradiation 6 y after the final publication of ESPAC-1 in 2004, highlighting the challenges of disseminating and adopting clinical data. After 2010, R1 disease was the most significant predictor of receiving adjuvant chemoradiation. Prospective studies are underway to definitively address the role of adjuvant chemoradiation in PDAC., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Adenosquamous carcinoma (ASC) of the pancreas is a rare form of malignancy with a poor prognosis. We herein report our case series with review of the contemporary literature., Methods: With institutional review board approval, we identified 23 patients with pancreatic ASC., Results: ASC was more common in women (61%), with a median age of 73 y at presentation. The tumor was in the head of the pancreas in 65% of cases. Six cases (26%) had resectable disease, three (13%) were borderline resectable, and eight (34.7%) were locally advanced or metastatic. First-line treatment included pancreatic resection in eight cases (34.8%), concurrent neoadjuvant chemoradiation in three (13%), and neoadjuvant chemotherapy in two (8.7%). Most resected tumors had pathological T3 stage (80%). Pathological nodal disease was demonstrated in 60%, and margins were positive in three cases. Complete pathological response was not observed, although fibrosis presented in only one case (10%). Eventually, twenty patients developed metastatic disease. Overall survival is 11.5 [95% confidence interval 6, 14.5] months., Conclusions: ASC demonstrates a more aggressive malignant phenotype and carries a worse prognosis. Oncological resection is the mainstay of treatment. Neoadjuvant chemoradiation is an emerging approach in the management of ASC that has been extrapolated from the adenocarcinoma neoadjuvant trials., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: Main controversies in endometrial cancer treatment include the role of lymphadenectomy and optimal adjuvant treatment. We assessed clinical outcome in a population-based endometrial cancer cohort in relation to changes in treatment management over two decades., Methods: All consenting endometrial cancer patients receiving primary treatment at Haukeland University Hospital from 2001 to 2019 were included (n = 1308). Clinicopathological variables were evaluated for year-to-year changes. Clinical outcome before and after discontinuing adjuvant radiotherapy and individualizing extent of lymphadenectomy was analyzed., Results: The rate of lymphadenectomy was reduced from 78% in 2001-2012 to 53% in 2013-2019. The rate of patients with verified lymph node metastases was maintained (9% vs 8%, p = 0.58) and FIGO stage I patients who did not undergo lymphadenectomy had stable 3-year recurrence-free survival (88% vs 90%, p = 0.67). Adjuvant chemotherapy for completely resected FIGO stage III patients increased from 27% to 97% from 2001 to 2009 to 2010-2019, while adjuvant radiotherapy declined from 57% to 0% (p < 0.001). These patients had improved 5-year overall- and recurrence-free survival; 0.49 [95% CI: 0.37-0.65] in 2001-2009 compared to 0.61 [0.45-0.83] in 2010-2019, p = 0.04 and 0.51 [0.39-0.68] to 0.71 [0.60-0.85], p = 0.03, respectively. For stage I, II and IV, survival rates were unchanged., Conclusions: Our study demonstrates that preoperative stratification by imaging and histological assessments permits a reduction in lymphadenectomy to around 50%, and is achievable without an increase in recurrences at 3 years. In addition, our findings support that adjuvant chemotherapy alone performs equally to adjuvant radiotherapy with regard to survival, and is likely superior in advanced stage patients., Competing Interests: Declaration of competing interest There are no conflicts of interest to disclose., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The aim of this systematic review and meta-analysis is to evaluate the efficacy and safety of adjuvant targeted therapy by sunitinib combined with surgery in the treatment of advanced or metastatic renal cell carcinoma., Methods: PubMed/Medline, Web of Science, Cochrane Library, ClinicalTrials.gov (http://www.ClinicalTrials.gov), China National Knowledge Infrastructure (CNKI) will be searched for clinical research articles related to the efficacy and safety of adjuvant therapy combined with surgery in the treatment of advanced and metastatic RCC. The identification, inclusion and exclusion flow charts will be conducted according to the PRISMA guidelines. The quality assessment will be done by Quadas-2 evaluation tool. Key parameters including OS in 10, 20, 30, and 40 months, PFS in 10, 20, and 30 months, objective response rate (ORR), stable disease (SD) rate, progressive disease (PD) rate, median OS and PFS, types of AEs and their occurrence rates, etc will be extracted. The evaluation of the efficacy and safety will be pooled by CMA., Results: This systematic review will provide evidence on the efficacy and safety of adjuvant therapy by sunitinib combined with surgery in treating advanced and metastatic RCC., Conclusion: The study aims to generalize data concerning the response rate, OS, PFS and rates of adverse effects of the perioperative use of sunitinib in advanced and metastatic RCC patients. The evidence provided by this systematic review and meta-analysis will help guide the clinical decision making and enlighten the future management of advanced or metastatic RCC., Registration: This protocol has been registered on the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY registration number: INPLASY2020110093; INPLASY DOI number: 10.37766/inplasy2020.11.0093 Available at: https://inplasy.com)., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Biliary tract cancer (BTC) includes a heterogeneous group of aggressive malignancies comprising gallbladder cancer (GBC), ampulla of Vater cancer (AVC), intrahepatic cholangiocarcinoma (iCCA), and extrahepatic cholangiocarcinoma (eCCA). Unfortunately, potentially curative resection is possible in approximately the 25% of presenting patients, and relapse rates are high, with a notable proportion of BTCs experiencing disease recurrence. Recent years have seen the publication of several prospective clinical trials evaluating the role of adjuvant systemic treatments, and among these, the phase III BILCAP study provided evidence supporting the use of capecitabine after radical surgery in BTC patients; in fact, although the study failed to meet its primary endpoint, the capecitabine arm showed improved clinical outcomes in terms of overall survival (pre-planned sensitivity analysis in the intention-to-treat population and in the per-protocol analysis) and relapse-free survival. However, the BILCAP has been widely criticized, with several authors that have not accepted adjuvant capecitabine as novel standard of care. In this review, we summarize current state of the art regarding adjuvant systemic treatment in BTC, highlighting advantages and disadvantages of recent clinical trials, and suggesting new research directions in this setting., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: Adjuvant chemotherapy for colon cancer with lymph node involvement (Stage III) has been the standard of care since the 1990s. Meanwhile, considerable evolvement of surgery combined with dedicated histopathological examinations may have led to stage migration. Furthermore, prognostic factors other than lymph node involvement have proven to affect overall survival. Thus, adjuvant chemotherapy in Stage III colon cancer should be reconsidered. The objective was to compare recurrence rates and survival in stage III colon cancer patients treated with or without adjuvant chemotherapy. Further, to assess the impact of extensive mesenterectomy, lymph node stage and vascular invasion on outcome., Methods: Consecutive patients operated for Stage III colon carcinoma between 31 December 2005 and 31 December 2015 were identified in the pathological code register by matching colon (T67) and either adenocarcinoma (M81403) or mucinous adenocarcinoma (M84803), with lymph node (T08) and metastasis of adenocarcinoma (M81406 or M84806). Medical records of all identified patients were reviewed., Results: Of 216 identified patients, 69 received no postoperative adjuvant chemotherapy (group NC), 69 insufficient adjuvant chemotherapy (FLV or < minimum recommended 6 cycles FLOX, group IC), and 78 sufficient adjuvant chemotherapy (≥ 6 cycles FLOX, group SC). When adjusted for age and comorbidity, 5-year overall survival did not differ statistically significant between groups (76% vs. 83% vs. 85%, respectively). Vascular invasion and a high lymph node ratio significantly reduced overall survival., Conclusion: The findings imply that subgroups of Stage III colon cancer patients have good prognosis also without adjuvant chemotherapy. For definite conclusions about necessity of adjuvant chemotherapy, prospective trials are needed.

Purpose: The summary presented herein represents Part I of the two-part series dedicated to Advanced Prostate Cancer: AUA/ASTRO/SUO Guideline discussing prognostic and treatment recommendations for patients with biochemical recurrence without metastatic disease after exhaustion of local treatment options as well as those with metastatic hormone-sensitive prostate cancer. Please refer to Part II for discussion of the management of castration-resistant disease., Materials and Methods: The systematic review utilized to inform this guideline was conducted by an independent methodological consultant. A research librarian conducted searches in Ovid MEDLINE (1998 to January Week 5 2019), Cochrane Central Register of Controlled Trials (through December 2018), and Cochrane Database of Systematic Reviews (2005 through February 6, 2019). An updated search was conducted prior to publication through January 20, 2020. The methodology team supplemented searches of electronic databases with the studies included in the prior AUA review and by reviewing reference lists of relevant articles., Results: The Advanced Prostate Cancer Panel created evidence- and consensus-based guideline statements to aid clinicians in the management of patients with advanced prostate cancer. Such statements are summarized in figure 1[Figure: see text] and detailed herein., Conclusions: This guideline attempts to improve a clinician's ability to treat patients diagnosed with advanced prostate cancer. Continued research and publication of high-quality evidence from future trials will be essential to improve the level of care for these patients.

Purpose: The summary presented herein represents Part II of the two-part series dedicated to Advanced Prostate Cancer: AUA/ASTRO/SUO Guideline discussing prognostic and treatment recommendations for patients with castration-resistant disease. Please refer to Part I for discussion of the management of patients with biochemical recurrence without metastatic disease after exhaustion of local treatment options as well as those with metastatic hormone-sensitive prostate cancer., Results: The Advanced Prostate Cancer Panel created evidence- and consensus-based guideline statements to aid clinicians in the management of patients with advanced prostate cancer. Such statements are summarized in figure 1[Figure: see text] and detailed herein., Materials and Methods: The systematic review utilized to inform this guideline was conducted by an independent methodological consultant. A research librarian conducted searches in Ovid MEDLINE (1998 to January Week 5 2019), Cochrane Central Register of Controlled Trials (through December 2018), and Cochrane Database of Systematic Reviews (2005 through February 6, 2019). An updated search was conducted prior to publication through January 20, 2020. The methodology team supplemented searches of electronic databases with the studies included in the prior AUA review and by reviewing reference lists of relevant articles., Conclusions: This guideline attempts to improve a clinician's ability to treat patients diagnosed with advanced prostate cancer. Continued research and publication of high-quality evidence from future trials will be essential to improve the level of care for these patients.

Introduction: The results of adjuvant chemotherapy trials in stage II and III colon cancer are often extrapolated to real-world patients. This study was conducted to determine the proportion of real-world patients with stage II/III colon cancer who would be eligible for adjuvant chemotherapy trials and to compare the outcomes among eligible versus ineligible patients., Patients and Methods: We identified all patients diagnosed with stage II/III colon cancer between 2004 and 2015 from a large province in Canada. Patients meeting any one of the following criteria were considered ineligible: age > 75 years, anemia, comorbid conditions (heart disease, uncontrolled diabetes, kidney disease, liver disease), and a history of malignancy or immunosuppression. Cox regression models were constructed to determine the factors predicting overall and cancer-specific survival., Results: A total of 7841 patients with stage II/III colon cancer were identified, of whom 52.0% were men and median age at diagnosis was 71 years. Approximately 58.6% of patients were deemed trial ineligible; the most common reasons for ineligibility included advanced age (36.2%), renal dysfunction (26.9%), and cardiac disease (17.4%). In the real-world setting, 54.0% of eligible patients received adjuvant chemotherapy compared to 23.2% of ineligible patients (odds ratio, 3.89; 95% confidence interval, 3.53-4.28; P < .0001). The 5-year overall and cancer-specific survival of trial-ineligible patients who received adjuvant chemotherapy was significantly better than those treated with surgery alone., Conclusion: The eligibility criteria of adjuvant chemotherapy trials in colon cancer should be broadened to be more representative of real-world patients., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: To investigate the survival outcomes of patients with stage IIIA colon cancer. In addition, risk factors that affect the oncologic outcome of stage IIIA colon cancer patients and the role of adjuvant chemotherapy were evaluated., Patients and Methods: Data from 326 colon cancer patients with stage IIIA who underwent surgery between January 2000 and December 2016 were retrospectively reviewed. Patients diagnosed with hereditary cancer and those who received preoperative neoadjuvant therapy were excluded., Results: The 5-year recurrence-free survival (RFS) rate in stage IIIA colon cancer patients who underwent curative resection was 93.9%. Of the patients with recurrence, the survival rate of those who underwent surgical resection was better than that of patients who received palliative chemotherapy or no treatment (12/13, 92.3% vs. 2/4, 50.0%), respectively; P = .052). Multivariate analysis showed that high serum carcinoembryonic antigen (s-CEA) was an independent and statistically significant prognostic factor for RFS, and ulcerative gross-type disease tended to be a poor prognostic factor. There was no difference in RFS in patients with elevated s-CEA or ulcerative gross-type disease according to receipt of adjuvant chemotherapy., Conclusion: Patients with stage IIIA colon cancer had a relatively favorable survival outcome. Even in patients with relapsed disease, long-term survival could be a result if surgical resection is accomplished. High s-CEA concentration is a significant poor prognostic factor for recurrence, and ulcerative gross-type disease tends to be a poor prognostic factor. Postoperative adjuvant chemotherapy may not provide a survival benefit for stage IIIA colon cancer, even in the presence of risk factors. Because of the rarity of this patient group and the low rate of recurrence, large-scale multicenter studies are needed to find and confirm the risk group that would receive a benefit from adjuvant chemotherapy., (Copyright © 2020. Published by Elsevier Inc.)

Trastuzumab emtansine (Kadcyla ® ), an antibody-drug conjugate of trastuzumab (Herceptin ® ) connected by a thioether linker to the microtubule inhibitor DM1 (a cytotoxic derivative of maytansine), provides direct intracellular delivery of the potent cytotoxin DM1 to HER2-overexpressing cells, while retaining trastuzumab activity. Its approval in metastatic/advanced breast cancer (BC) has been extended to include single-agent adjuvant treatment of HER2-positive early BC in patients with residual invasive disease in the breast and/or lymph nodes after neoadjuvant taxane-based and HER2-targeted treatment. In the pivotal KATHERINE trial in this population, significantly more trastuzumab emtansine than trastuzumab recipients were estimated to be free of invasive disease recurrence at 3 years, with a 50% reduction in the risk of invasive disease recurrence or death. The tolerability of trastuzumab emtansine in early BC was consistent with its known safety profile; as expected, adverse events were more common with trastuzumab emtansine than with trastuzumab. Recently updated international and national treatment guidelines recommend trastuzumab emtansine as a preferred option in this high-risk BC population.

Approximately 20% of all breast cancers overexpress the human epidermal growth factor receptor 2 (HER2). Targeting breast cancer through this vital oncogenic protein has been a major step towards improved patient outcomes. Today, several anti-HER2 agents are in clinical use including: the monoclonal antibodies trastuzumab and pertuzumab; the small molecule inhibitors lapatinib, neratinib, and tucatinib; and the antibody-drug conjugates ado-trastuzumab emtansine and trastuzumab deruxtecan, in some jurisdictions. In addition, several trastuzumab biosimilars have recently been granted regulatory approval in North America and the EU, and are enhancing patient access to HER2-directed therapy. The various agents differ greatly in their side-effect profiles and approved indications, from neoadjuvant and adjuvant use in early disease, to first- and later-line use in metastatic disease. This review discusses the current treatment recommendations for the use of anti-HER2 agents alone and in combination, examines the latest advances in HER2-targeted drugs and how they may be best applied in clinical practice, and provides guidance on optimal sequencing of the growing array of therapeutic options for HER2-positive breast cancer.

Objective: The Japan Society of Gynecologic Oncology published its first clinical guidelines for uterine cervical cancer in 2007 which has been revised twice in 2011 and 2017. The aim of this study was to investigate the influence of the first guideline publication on the therapeutic trend and patient outcome by analyzing uterine cervical cancer cases registered to the cancer registry organized by the Japan Society of Obstetrics and Gynecology., Methods: Data of uterine cervical cancer cases registered to the cancer registry from 2000 to 2012 were provided. Epidemiological and clinical trend were analyzed by the Chi-squared test with subsequent standardized residual analysis. Overall survival among the patients registered between 2004 and 2009 was analyzed using the Fine and Gray competing risk model., Results: 68,707 cases were registered during the study period. A trend analysis revealed that the guideline publication may have led to a decrease in neoadjuvant chemotherapy in parallel with an increase in radiation therapy mainly in stage II and III patients undergoing primary treatment. A survival analysis indicated that the introduction of the guideline may have improved overall survival among stage III uterine cervical cancer patients, even though a significant difference was not observed in all of the cases., Conclusions: This study demonstrated the potential influence of the guideline publication on the clinical trend and patient outcome. As this is the first assessment of the guideline for uterine cervical cancer in Japan, continuous evaluation is necessary to further comprehend the significance of this guideline., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to disclose regarding to this study., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: This systematic review assessed compliance to guidelines for the management of nonmuscle-invasive bladder carcinoma (NMIBC)., Methods: The PUBMED, Web of Science, Cochrane Library, and Scopus databases were searched in November 2019 in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis statement., Results: Fifteen studies incorporating a collective total of 10,575 NMIBC patients were eligible for inclusion in this systematic review. We found that the rates of compliance were 53.0% with a single immediate intravesical instillation in patients with presumed low or intermediate risk, 37.1% with intravesical bacillus Calmette-Guerin or chemotherapy in those with intermediate risk, 43.4% with performance of a second transurethral resection in high-risk patients, 32.5% with administration of adjuvant intravesical bacillus Calmette-Guerin in high-risk patients, 36.1% with radical cystectomy in highest-risk patients, and 82.2% with cystoscopy for follow-up., Conclusions: Compliance with NMIBC guidelines remains low. Better guideline education and understanding holds the key to achieving high compliance. Strategies to improve guideline compliance at the physician level are urgently required., (Copyright © 2020. Published by Elsevier Inc.)

Objective: Ultra-radical surgery to achieve complete resection in advanced epithelial ovarian cancer (EOC) has been widely accepted without strong supporting data. Our objective was to assess overall survival after a structured shift to an ultra-radical upfront surgical treatment algorithm and to investigate changes in the distribution of primary treatments after this shift., Patients and Methods: In this population-based cohort study, all women with suspected EOC in the Stockholm-Gotland region of Sweden reported to the Swedish Quality Registry for Gynecologic Cancer (SQRGC) and National Cancer Registry (NCR) were selected in two 3-year cohorts, based on year of diagnosis (before (cohort1) or after (cohort 2) change in surgical treatment algorithm) and followed for at least three years. 5-year overall survival (OS) in non-surgically and surgically treated women was analyzed. Moreover, proportional distribution of primary treatment was evaluated., Results: 752 women were included in the final analysis (n = 364 and 388 in cohort 1 and 2 respectively) with a median follow-up of 29 and 27 months. The complete resection rate increased from 37 to 67% (p ≤ 0.001) as well as proportion non-surgically treated women, 24 to 33%. No improvement in OS was observed in non-surgically (HR 0.76 (95% CI, 0.58-1.01); p = 0.06) or surgically treated (HR 0.94 (95% CI, 0.75-1.18); p = 0.59) women, even when complete resection was achieved (HR 1.31 (95% CI, 0.89-1.92); p = 0.17)., Conclusion: A shift to ultra-radical upfront surgery in EOC did not improve survival despite a significant increase in complete resection rate. Identifying the limitations of surgical treatment remains a challenge., Competing Interests: Declaration of competing interest All authors declare no conflicts of interest., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: Today, the rapid outbreak of COVID-19 is the leading health issue. Patients with cancer are at high risk for the development of morbidities of COVID-19. Hence, oncology centers need to provide organ-based recommendations for optimal management of cancer in the COVID-19 era., Methods: In this article, we have provided the recommendations on management of locally advanced rectal cancer during the COVID-19 pandemic based on our experience in Shohada-e Tajrish Hospital, Iran., Results: We recommend that patients with locally advanced rectal cancer should be managed in an individualized manner in combination with local conditions related to COVID-19., Conclusion: Our recommendation may provide a guide for oncology centers of developing countries for better management of locally advanced rectal cancer.

Purpose: Despite advances in various treatment modalities, surgical resection for pancreatic ductal adenocarcinoma (PDA) remains the only curative treatment. Data remains limited regarding survival rates for resectable PDA when managed by a multidisciplinary pancreas conference (MDPC). The aim of this study is to assess survival rates, identify significant predictors of mortality, and assess the benefits of adjuvant chemotherapy for resectable PDA following presentation at a MDPC., Methods: All patients presented from April 2013 to August 2016 with resectable PDA were discussed at a MDPC at a tertiary care center and were followed prospectively until November 2017. Survival analysis was performed using Kaplan-Meier for age, tumor size, tumor differentiation, T-stage, lymph node status, and completion of adjuvant chemotherapy cycles. Independent predictors of survival were determined using multivariate Cox regression modeling., Results: After MDPC consensus and exclusions, total of 64 patients underwent successful surgery. Amongst this cohort, 1-, 2-, and 3-year survival was 78.13%, 46.30%, and 27.27%, respectively. A total of 37 patients (58%) initiated and 16 patients (25%) finished chemotherapy following surgery. Log-rank analysis revealed that tumor size, age, surgical margins, lymph node status, and number of adjuvant chemotherapy cycles received significantly influenced post-operative survival. Tumor size (p < 0.001), lymph node status (p = 0.035), and number of adjuvant chemotherapy cycles (p = 0.041) remained significant after multivariate Cox regression model., Conclusions: Our results suggest that patients with PDA with tumor size > 50 mm and/or lymph node involvement have poor outcomes despite being surgically resectable. Successful completion of adjuvant chemotherapy has better survival outcomes as compared with incomplete or no adjuvant chemotherapy. The role of alternative management such as down-staging with neoadjuvant therapy should be considered.

Background: Accurate detection of patients with minimal residual disease (MRD) after surgery for stage II colon cancer (CC) remains an urgent unmet clinical need to improve selection of patients who might benefit form adjuvant chemotherapy (ACT). Presence of circulating tumor DNA (ctDNA) is indicative for MRD and has high predictive value for recurrent disease. The MEDOCC-CrEATE trial investigates how many stage II CC patients with detectable ctDNA after surgery will accept ACT and whether ACT reduces the risk of recurrence in these patients., Methods/design: MEDOCC-CrEATE follows the 'trial within cohorts' (TwiCs) design. Patients with colorectal cancer (CRC) are included in the Prospective Dutch ColoRectal Cancer cohort (PLCRC) and give informed consent for collection of clinical data, tissue and blood samples, and consent for future randomization. MEDOCC-CrEATE is a subcohort within PLCRC consisting of 1320 stage II CC patients without indication for ACT according to current guidelines, who are randomized 1:1 into an experimental and a control arm. In the experimental arm, post-surgery blood samples and tissue are analyzed for tissue-informed detection of plasma ctDNA, using the PGDx elio™ platform. Patients with detectable ctDNA will be offered ACT consisting of 8 cycles of capecitabine plus oxaliplatin while patients without detectable ctDNA and patients in the control group will standard follow-up according to guideline. The primary endpoint is the proportion of patients receiving ACT when ctDNA is detectable after resection. The main secondary outcome is 2-year recurrence rate (RR), but also includes 5-year RR, disease free survival, overall survival, time to recurrence, quality of life and cost-effectiveness. Data will be analyzed by intention to treat., Discussion: The MEDOCC-CrEATE trial will provide insight into the willingness of stage II CC patients to be treated with ACT guided by ctDNA biomarker testing and whether ACT will prevent recurrences in a high-risk population. Use of the TwiCs design provides the opportunity to randomize patients before ctDNA measurement, avoiding ethical dilemmas of ctDNA status disclosure in the control group., Trial Registration: Netherlands Trial Register: NL6281/NTR6455 . Registered 18 May 2017, https://www.trialregister.nl/trial/6281.

Background: It is estimated that around 15-30% of patients with early stage colon cancer benefit from adjuvant chemotherapy. We are currently not capable of upfront selection of patients who benefit from chemotherapy, which indicates the need for additional predictive markers for response to chemotherapy. It has been shown that the consensus molecular subtypes (CMSs), defined by RNA-profiling, have prognostic and/or predictive value. Due to postoperative timing of chemotherapy in current guidelines, tumor response to chemotherapy per CMS is not known, which makes the differentiation between the prognostic and predictive value impossible. Therefore, we propose to assess the tumor response per CMS in the neoadjuvant chemotherapy setting. This will provide us with clear data on the predictive value for chemotherapy response of the CMSs., Methods: In this prospective, single arm, multicenter intervention study, 262 patients with resectable microsatellite stable cT3-4NxM0 colon cancer will be treated with two courses of neoadjuvant and two courses of adjuvant capecitabine and oxaliplatin. The primary endpoint is the pathological tumor response to neoadjuvant chemotherapy per CMS. Secondary endpoints are radiological tumor response, the prognostic value of these responses for recurrence free survival and overall survival and the differences in CMS classification of the same tumor before and after neoadjuvant chemotherapy. The study is scheduled to be performed in 8-10 Dutch hospitals. The first patient was included in February 2020., Discussion: Patient selection for adjuvant chemotherapy in early stage colon cancer is far from optimal. The CMS classification is a promising new biomarker, but a solid chemotherapy response assessment per subtype is lacking. In this study we will investigate whether CMS classification can be of added value in clinical decision making by analyzing the predictive value for chemotherapy response. This study can provide the results necessary to proceed to future studies in which (neo) adjuvant chemotherapy may be withhold in patients with a specific CMS subtype, who show no benefit from chemotherapy and for whom possible new treatments can be investigated., Trial Registration: This study has been registered in the Netherlands Trial Register (NL8177) at 11-26-2019, https://www.trialregister.nl/trial/8177 . The study has been approved by the medical ethics committee Utrecht (MEC18/712).

Opinion Statement: Hormone receptor (HR) positive breast cancer has a high propensity for late recurrences that might be prevented with longer durations of endocrine therapy (ET). However, trials evaluating extended adjuvant ET have produced somewhat conflicting results. Additionally, ET is associated with not only day to day side effects that can impact quality of life, but more detrimental effects that can cause significant morbidity. Although patients with higher stage disease are at greater risk of late recurrences, even patients with stage 1 disease have a significant risk of recurrence after 5 years. Current guidelines recommend extending therapy for patients with node-positive disease, but recommendations for patients with node-negative disease are less clear. This has led to the development of various genomic tests to aid oncologists in further individualizing their approach when it comes to deciding which subpopulation of patients with HR-positive breast cancer may benefit from extending their endocrine therapy beyond 5 years. There are several assays that are prognostic of recurrences years 6 to 10 following diagnosis. Additionally, the breast cancer index has been shown to be predictive of extended ET in patients who have completed 5 years of tamoxifen. None of the available assays are, to date, predictive of recurrence after 10 years. Genomic testing is not appropriate for all patients, especially if the results will not predict the choice of further treatment. Ultimately, genomic testing should help facilitate shared decision making between the patient and oncologist.

Background: Tyrosine kinase inhibitor-based adjuvant therapy showed no survival benefits for patients with high-risk nonmetastatic renal cell carcinoma (nmRCC). Five randomized immune-oncology checkpoint inhibitor trials are ongoing. We assessed the effect of stage, grade, and histologic type on cancer-specific mortality (CSM) in candidates for 1 of the 4 North American ongoing immune-oncology checkpoint inhibitor trials of high-risk nmRCC., Patients and Methods: From the Surveillance, Epidemiology, and End Results database (2001-2015), we identified patients who had undergone surgery for nmRCC and had met the inclusion criteria for the PROSPER RCC (nivolumab in treating patients with localized kidney cancer undergoing nephrectomy), CheckMate 914 (a study comparing the combination of nivolumab and ipilimumab versus placebo in participants with localized renal cell carcinoma), KEYNOTE-564 [safety and efficacy study of pembrolizumab (MK-3475) as monotherapy in the adjuvant treatment of renal cell carcinoma post nephrectomy], or IMmotion010 [a study of atezolizumab as adjuvant therapy in participants with renal cell carcinoma (RCC) at high risk of developing metastasis following nephrectomy] trials. Kaplan-Meier and multivariable Cox regression models were used to assess the 10-year CSM rates in the overall cohort according to stage, grade, and histologic characteristics, and in 4 generated random samples according to the eligible patients for each of the 4 trials., Results: Of 116,750 patients who had undergone surgery for nmRCC, 18,559 (15.9%) had fulfilled the inclusion criteria for 1 of the 4 trials. The greatest proportion of higher stage and grade combinations and sarcomatoid histologic features would have qualified for IMmotion010, followed by KEYNOTE-564, CheckMate 914, and PROSPER RCC. Multivariable Cox regression models demonstrated the most unfavorable prognosis for stage N1 grade 3/4 (hazard ratio [HR], 11.5; P < .001), stage T4N0 grade 3/4 (HR, 9.8; P < .001), and sarcomatoid histologic features (HR, 5.5; P < .001). Among the 4 random samples, the difference in the qualifying criteria resulted in the greatest versus progressively lower CSM rates in the IMmotion010, KEYNOTE-564, CheckMate 914, and PROSPER RCC trials, respectively (P < .001)., Conclusions: Our findings indicate that participation in adjuvant immunotherapy trials should be predominantly encouraged for patients with high-grade stage T3, T4, and N1 and patients with any stage with sarcomatoid pathologic features., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Small-cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare and highly aggressive ovarian malignancy. In almost all cases, it is associated with somatic and often germline pathogenic variants in SMARCA4 , which encodes for the SMARCA4 protein (BRG1), a subunit of the SWI/SNF chromatin remodeling complex. Approximately 20% of human cancers possess pathogenic variants in at least one SWI/SNF subunit. Because of their role in regulating many important cellular processes including transcriptional control, DNA repair, differentiation, cell division, and DNA replication, SWI/SNF complexes with mutant subunits are thought to contribute to cancer initiation and progression. Fewer than 500 cases of SCCOHT have been reported in the literature and approximately 60% are associated with hypercalcemia. SCCOHT primarily affects females under 40 years of age who usually present with symptoms related to a pelvic mass. SCCOHT is an aggressive cancer, with long-term survival rates of 30% in early-stage cases. Although various treatment approaches have been proposed, there is no consensus on surveillance and therapeutic strategy. An international group of multidisciplinary clinicians and researchers recently formed the International SCCOHT Consortium to evaluate current knowledge and propose consensus surveillance and therapeutic recommendations, with the aim of improving outcomes. Here, we present an overview of the genetics of this cancer, provide updates on new treatment targets, and propose management guidelines for this challenging cancer., (©2020 American Association for Cancer Research.)

In addition to classical clinicopathologic factors, such as hormone receptor positivity, human epidermal growth factor receptor 2 (HER2) status, and tumor size, grade, and lymph node status, a number of commercially available genomic tests may be used to help inform treatment decisions for early breast cancer patients. Although these tests improve our understanding of breast cancer and help to individualize treatment decisions, clinicians face challenges when deciding on the most appropriate test to order, and the advantages, if any, of one test over another. The Breast Cancer Therapy Expert Group (BCTEG) recently convened a roundtable meeting to discuss issues surrounding the use of genomic testing in early breast cancer, with the goal of providing practical guidance on the use of these tests by the community oncologist, for whom breast cancer may be only one of many tumor types they treat. The group recognizes that genomic testing can provide important prognostic (eg, risk for recurrence), and in some cases predictive, information (eg, benefit of chemotherapy, or extended adjuvant endocrine therapy), which can be used to help guide treatment decisions in breast cancer. The available tests differ in the types of information they provide, and in the patient populations and clinical trials that were conducted to validate them. We summarize the discussion of the BCTEG on this topic, and we also consider several patient cases and clinical scenarios in which genomic testing may, or may not, be useful to guide treatment decisions for the practicing community oncologist., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Expression of human epidermal growth factor receptor 2 (HER2) in breast cancer defines a subset of patients (∼15%-20%) who are candidates for anti-HER2 therapies, most notably, trastuzumab, pertuzumab, antibody drug conjugates (eg, T-DM1), and tyrosine kinase inhibitor (TKI) drugs (eg, lapatinib and neratinib), all of which have dramatically changed the prognosis for this aggressive subtype of breast cancer. A roundtable meeting of the Breast Cancer Therapy Expert Group (BCTEG) was convened in March 2018 in an effort to discuss and clarify, from the perspective of the practicing community oncologist, recent developments in the diagnosis and treatment of HER2-positive (HER2 + ) breast cancer. Members of the group selected 4 key topics for discussion prior to the meeting, including diagnosis of HER2 + disease, and its treatment in the neoadjuvant, adjuvant, and metastatic settings. Approved testing methods, such as immunohistochemistry and fluorescence in situ hybridization, are used to demonstrate overexpression and/or amplification of HER2 in breast tumors, and established clinical guidelines are used to appropriately define treatment plans for patients with HER2 + disease. The panel acknowledges a range of treatment options now available for treatment of HER2 + breast cancer in the neoadjuvant, adjuvant, and advanced/metastatic settings, although it is noted that many controversies remain, including the optimal sequence of therapies, the most appropriate treatment(s) for subsets of patients with HER2 + disease (eg, hormone receptor-negative or -positive/HER2 + ), and uncertainties surrounding the diagnosis and definition of HER2 + disease. The current report summarizes the discussion of the BCTEG panel on this topic., (Copyright © 2019. Published by Elsevier Inc.)

Introduction: Recent studies have questioned the relative benefit of radiotherapy (RT) for older patients with favorable breast cancer given the lack of survival benefit and marginal local control benefit. Despite the 2004 National Comprehensive Cancer Network (NCCN) guidelines advocating for the option of hormonal therapy alone, trends in utilization rates of RT in this group are not well-documented. We analyzed our institutional experience with implementation of the guidelines over time., Material and Methods: We identified 564 patients aged ≥ 60 years with favorable breast cancer treated with breast conserving surgery from 2000 to 2017. Patients met criteria for Cancer and Leukemia Group B (CALGB) 9343, Postoperative Radiotherapy in Minimum Risk Elderly (PRIME II), or the very-low risk cohort identified in the Toronto-British Columbia study. Multivariable logistic regression analysis was performed to assess the magnitude of association between omission status, grade, and tumor size while controlling for age and year of diagnosis., Results: Overall RT omission rates were 17.6% prior to the 2004 NCCN update and 45% after the publication of the 10-year CALGB data in 2013. The overall RT omission rate was 29%. Patients with grade 1 to 2 histology (odds ratio, 3.2; 95% confidence interval, 1.3-7.7; P = .01) and tumors < 1 cm (odds ratio, 1.60; 95% confidence interval, 0.4-0.9; P = .007) were more likely to omit RT than those with higher grade or larger tumors., Conclusions: We observed a slight decrease in the use of RT over time, suggesting a move towards adoption of the NCCN guidelines. There remains a fundamental need to continue to individualize breast cancer care based on risk stratification and make evidenced-based treatment recommendations with equitable use of health care resources., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Ductal carcinoma in situ (DCIS) represents 15% of all breast cancers in France. The first national survey was conducted in 2003. The present multi-center real-life practice survey aimed at assessing possible changes in demographic, clinical, pathologic, and treatment features., Material and Methods: From March 2014 to September 2015, patients diagnosed with DCIS from 71 centers with complete information about age, diagnostic features, and treatment modalities were prospectively included., Results: A total of 2125 patients with a median age of 58.6 years from 71 centers were studied. DCIS was diagnosed by mammography in 87.5% of cases. Preoperative biopsy was performed in 96% of cases. The median tumor size was 15 mm. Nuclear grade was low, intermediate, and high in 12%, 36%, and 47% of cases, respectively. Margins were considered to be negative in 83% of cases. Overall mastectomy and lumpectomy rates were 25% and 75%, respectively. The immediate breast reconstruction rate was 50%. Sentinel node biopsy and axillary dissection rates were 41% and 2.6%, respectively. After lumpectomy, 97% of patients underwent radiotherapy, and 32% received a boost dose. Only 1% of patients received endocrine therapy. Compared with our previous survey, the median tumor size remained the same, and the proportion of high-grade lesions increased by 9%. The mastectomy rate decreased by 4%., Conclusions: The clinical practice identified in this survey complies with French DCIS guidelines. About 10% of patients with low-grade DCIS may be eligible to participate in treatment de-escalation trials., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: This study aimed to compare the survival outcomes of radio-chemotherapy (R-CT) and radical hysterectomy with postoperative standard therapy (RH) in stage IB1-IIA2 cervical cancer patients., Methods: Based on the large amount of diagnostic and treatment cervical cancer data in China, a real-world study and 1:1 case-control matching were used to compare overall survival (OS) and disease-free survival (DFS) in cervical cancer patients., Results: In this real-world study, the 5-year OS and DFS in the R-CT group (n = 8949) were lower than those in the RH group (n = 18,152). After applying the inclusion criteria, the OS and DFS in the R-CT group (n = 582) were lower than those in the RH group (n = 4308). After 1:1 case-control matching, the 5-year OS and DFS in the R-CT group (n = 535) were lower than those in the RH group (n = 535) (OS: 76.1% vs. 84.6%, p < 0.001, HR = 1.819; DFS: 75.1% vs. 81.5%, p < 0.001, HR = 1.462, respectively). Further stratification showed that for stage IB1 and IIA1 patients, the 5-year OS and DFS in the R-CT group (n = 300) were lower than those in the RH group (n = 300) (OS: 78.9% vs. 87.0%, p < 0.001, HR = 2.160; DFS: 77.0% vs. 84.9%, p < 0.001, HR = 2.053, respectively). In stage IB2 and IIA2 patients, the 5-year OS in the R-CT group (n = 235) was lower than that in the RH group (n = 235) (72.5% vs. 81.5%, p = 0.039; HR = 1.550), but no difference in the 5-year DFS was found between the two groups (72.6% vs. 76.9%, p = 0.151)., Conclusions: Our study found that for stage IB1-IIA2 cervical cancer patients, RH offers better overall survival and disease-free survival outcomes than R-CT, however, due to the inherent biases of retrospective study, it needs to be confirmed by randomized trials. In addition, we need to further understand the quality of life of the two treatments., Trial Registration: registration number: CHiCTR1800017778; International Clinical Trials Registry Platform Search Port, http://apps.who.int/trialsearch/. registration date: August 14, 2018.

Biliary tract cancer, including cholangiocarcinoma (CCA) and gallbladder cancer (GBC) are rare tumours with a rising incidence. Prognosis is poor, since most patients are diagnosed with advanced disease. Only ~20% of patients are diagnosed with early-stage disease, suitable for curative surgery. Despite surgery performed with potentially-curative intent, relapse rates are high, with around 60-70% of patients expected to have disease recurrence. Most relapses occur in the form of distant metastases, with a predominance of liver spread. In view of high tumour recurrence, adjuvant strategies have been explored for many years, in the form of radiotherapy, chemo-radiotherapy and chemotherapy. Historically, few randomised trials were available, which included a variety of additional tumours (e.g. pancreatic and ampullary tumours); most evidence relied on phase II and retrospective studies, with no high-quality evidence available to define the real benefit derived from adjuvant strategies. Since 2017, three randomised phase III clinical trials have been reported; all recruited patients with resected biliary tract cancer (CCA and GBC) who were randomised to observation alone, or chemotherapy in the form of gemcitabine (BCAT study; included patients diagnosed with extrahepatic CCA only), gemcitabine and oxaliplatin (PRODIGE-12/ACCORD-18; included patients diagnosed with CCA and GBC) or capecitabine (BILCAP; included patients diagnosed with CCA and GBC). While gemcitabine-based chemotherapy failed to show an impact on patient outcome (relapse-free survival (RFS) or overall survival (OS)), the BILCAP study showed a benefit from adjuvant capecitabine in terms of OS (pre-planned sensitivity analysis in the intention-to-treat population and in the per-protocol analysis), with confirmed benefit in terms of RFS. Based on the BILCAP trial, international guidelines recommend adjuvant capecitabine for a period of six months following potentially curative resection of CCA as the current standard of care for resected CCA and GBC. However, BILCAP failed to show OS benefit in the intention-to-treat (non-sensitivity analysis) population (primary end-point), and this finding, as well as some inconsistencies between studies has been criticised and has led to confusion in the biliary tract cancer medical community. This review summarises the adjuvant field in biliary tract cancer, with evidence before and after 2017, and comparison between the latest randomised phase III studies. Potential explanations are presented for differential findings, and future steps are explored., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Neoadjuvant therapy is an increasing treatment option in the management of breast cancer. The tumor response to neoadjuvant therapy, especially the pathological complete response, is a validated endpoint frequently used in clinical trials. However, there is still a lack of standardization for the surgical specimen management in the neoadjuvant setting. This leads to heterogeneity in the specimen handling and might lead to significant bias for the prognostic assessment of patients or in clinical trials. The GEFPICS group, composed of expert breast cancer pathologists, herein presents guidelines for the management of breast and axillary specimen before treatment (management of biopsy, items of the pathological report) and after neoadjuvant therapy (specimen handling, histological assessment of response, items of the pathological report and response grading systems)., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Objectives: To investigate the treatment pattern of non-muscle invasive bladder cancer patients among urologists in Japan, Korea and Taiwan, with emphasis on compliance with important treatment guidelines., Methods: A Web-based questionnaire survey was conceived by representative members of each country's urological oncology society and was open from June 2016 to February 2017 to each society's members. Descriptive statistics and multinomial logistic regression analysis were used., Results: A total of 2334 urologists were invited and 701 responded to the survey with a response rate of 30.0%. Instruments used during transurethral resection of bladder cancer varied significantly between countries and depended on their availability. The re-transurethral resection rate for pT1 or high-grade disease >50% of the time was significantly higher in Japan than in the other two countries, but the collective rate was just 49%. The frequency of intravesical therapy in intermediate- to high-risk disease was generally consistent across countries. However, the choice of agent between chemotherapy and bacillus Calmette-Guérin was significantly different between countries. Maintenance bacillus Calmette-Guérin was used <10% of the time by 45% of respondents, the most important reasons being fear of side-effects, followed by a lack of efficacy and shortage of drug supply., Conclusions: There are significant differences between Japan, Korea and Taiwan in the management of intermediate- to high-risk non-muscle invasive bladder cancer. The results of this survey can serve as the basis for joint efforts to develop common clinical guidelines., (© 2019 The Japanese Urological Association.)

In December 2017, ESMO Open-Cancer Horizons convened a round-table discussion on the background and latest data regarding cyclin-dependent kinase (CDK)4/6 inhibitors with endocrine therapy (ET) in the treatment of endocrine-sensitive breast cancer (BC). A review on this discussion was published in summer 2018 (https://esmoopen.bmj.com/content/3/5/e000368).Endocrine-sensitive BC with non-visceral disease and limited spread of the metastases.Endocrine-sensitive BC with non-life-threatening visceral involvement. Several open questions were identified, which led to a second ESMO Open discussion on CDK4/6 inhibitors, taking place in December 2018 and covered in this article. The panel discussed two important clinical scenarios and the pro and cons of a treatment approach with CDK4/6 inhibitors for each scenario:Endocrine-sensitive BC with non-visceral disease and limited spread of the metastases.Endocrine-sensitive BC with non-life-threatening visceral involvement. Regarding scenario 1, the panel agreed that CDK4/6 inhibitors should be recommended in first-line therapy for most patients if cost and practicality allow. However, the use of single-agent ET with an aromatase inhibitor in the first-line treatment of these patients is still a possibility for a small group of patients with very limited disease, such as one or two bone lesions or limited lymph node involvement. Regarding scenario 2, chemotherapy is the first approach for patients with endocrine-sensitive metastatic BC with life-threatening visceral involvement because of the need for a faster response. The therapeutic approaches for patients with non-life-threatening visceral involvement are still under debate. Nevertheless, CDK4/6 inhibitors are currently the treatment of choice for most patients with a close follow-up of tumour response. A treatment algorithm has been suggested at the round table., Competing Interests: Competing interests: MP: honoraria for lectures, consultation or advisory board participation from the following for-profit companies: Bayer, Bristol-Myers Squibb, Novartis, Gerson Lehrman Group (GLG), CMC Contrast, GlaxoSmithKline, Mundipharma, Roche, Astra Zeneca, AbbVie, Lilly, Medahead, Daiichi Sankyo and Merck Sharp & Dome. JG: research support from Eisai, Genomic Health, Novartis, Pfizer and Roche; travel grants from Eisai, Genomic Health, Novartis, Pfizer and Roche; honoraria for advisory boards and speaker fees from Daiichi, Eisai, Genomic Health, Ipsen, Macrogenics, MSD, Novartis, Onxeo, Pfizer and Roche. GJ: grants, personal fees and non-financial support from Novartis and Roche; personal fees and non-financial support from Pfizer, Lilly, Amgen, BMS, Astra-Zeneca; personal fees from Celgene, Puma Technology, Daiichi Sankyo and Abbvie. AA: advisory boards, travel grants, speaker fees: Novartis, Roche, Lilly, Amgen, Eisai, BMS, MSD, LeoPharma, Genomic Health and Ipsen. CS: honoraria for lectures, consultation or advisory board participation from the following for-profit companies: Novartis, Gerson Lehrman Group, Astra-Zeneca, Lilly, Roche, Amgen, Pfitzer, Merck KGaA, and Tesaro. CCZ: honoraria from Roche, Novartis, BMS, MSD, Imugene, Ariad, Pfizer, Merrimack, Merck KGaA, Fibrogen, AstraZeneca, Tesaro, Gilead, Servier and Shire., (© Author (s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ on behalf of the European Society for Medical Oncology.)

Introduction: Stereotactic body radiotherapy (SBRT) is a non-invasive alternative to surgery for the treatment of non-metastatic prostate cancer (PC). The objectives of the Novel Integration of N ew prostate radiation schedules with adJuvant Androgen deprivation (NINJA) clinical trial are to compare two emerging SBRT regimens for efficacy with technical substudies focussing on MRI only planning and the use of knowledge-based planning (KBP) to assess radiotherapy plan quality., Methods and Analysis: Eligible patients must have biopsy-proven unfavourable intermediate or favourable high-risk PC, have an Eastern Collaborative Oncology Group (ECOG) performance status 0-1 and provide written informed consent. All patients will receive 6 months in total of androgen deprivation therapy. Patients will be randomised to one of two SBRT regimens. The first will be 40 Gy in five fractions given on alternating days (SBRT monotherapy). The second will be 20 Gy in two fractions given 1 week apart followed 2 weeks later by 36 Gy in 12 fractions given five times per week (virtual high-dose rate boost (HDRB)). The primary efficacy outcome will be biochemical clinical control at 5 years. Secondary endpoints for the initial portion of NINJA look at the transition of centres towards MRI only planning and the impact of KBP on real-time (RT) plan assessment. The first 150 men will demonstrate accrual feasibility as well as addressing the KBP and MRI planning aims, prior to proceeding with total accrual to 472 patients as a phase III randomised controlled trial., Ethics and Dissemination: NINJA is a multicentre cooperative clinical trial comparing two SBRT regimens for men with PC. It builds on promising results from several single-armed studies, and explores radiation dose escalation in the Virtual HDRB arm. The initial component includes novel technical elements, and will form an important platform set for a definitive phase III study., Trial Registration Number: ANZCTN 12615000223538., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Many older patients don't receive appropriate oncological treatment. Our aim was to analyse whether there are age differences in the use of adjuvant chemotherapy and preoperative radiotherapy in patients with colorectal cancer., Methods: A prospective cohort study was conducted in 22 hospitals including 1157 patients with stage III colon or stage II/III rectal cancer who underwent surgery. Primary outcomes were the use of adjuvant chemotherapy for stage III colon cancer and preoperative radiotherapy for stage II/III rectal cancer. Generalised estimating equations were used to adjust for education, living arrangements, area deprivation, comorbidity and clinical tumour characteristics., Results: In colon cancer 92% of patients aged under 65 years, 77% of those aged 65 to 80 years and 27% of those aged over 80 years received adjuvant chemotherapy (χ 2 trends  < 0.001). In rectal cancer preoperative radiotherapy was used in 68% of patients aged under 65 years, 60% of those aged 65 to 80 years, and 42% of those aged over 80 years (χ 2 trends  < 0.001). Adjusting by comorbidity level, tumour characteristics and socioeconomic level, the odds ratio of use of chemotherapy compared with those under age 65, was 0.3 (0.1-0.6) and 0.04 (0.02-0.09) for those aged 65 to 80 and those aged over 80, respectively; similarly, the odds ratio of use of preoperative radiotherapy was 0.9 (0.6-1.4) and 0.5 (0.3-0.8) compared with those under 65 years of age., Conclusions: The probability of older patients with colorectal cancer receiving adjuvant chemotherapy and preoperative radiotherapy is lower than that of younger patients; many of them are not receiving the treatments recommended by clinical practice guidelines. Differences in comorbidity, tumour characteristics, curative resection, and socioeconomic factors do not explain this lower probability of treatment. Research is needed to identify the role of physical and cognitive functional status, doctors' attitudes, and preferences of patients and their relatives, in the use of adjuvant therapies.

The peritoneum is a common site of dissemination for colorrectal cancer, with a poorer prognosis than other sites of metastases. In the last two decades, it has been considered as a locoregional disease progression and treated as such with curative intention treatments. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is the actual reference treatment for these patients as better survival results have been reached as compared to systemic chemotherapy alone, but its therapeutic efficacy is still under debate. Actual guidelines recommend that the management of colorectal cancer with peritoneal metastases should be led by a multidisciplinary team carried out in experienced centers and consider CRS + HIPEC for selected patients. Accumulative evidence in the last three years suggests that this is a curative treatment that may improve patients disease-free survival, decrease the risk of recurrence, and does not increase the risk of treatment-related mortality. In this review we aim to gather the latest results from referral centers and opinions from experts about the effectiveness and feasibility of CRS + HIPEC for treating peritoneal disease from colorectal malignancies., Competing Interests: Conflict-of-interest statement: Any author has any potential conflicts of interest to declare. No financial support was received for this review.

Introduction: Contemporary guidelines recommend cystectomy with neoadjuvant or adjuvant cisplatin-based chemotherapy given with curative intent for patients with resectable muscle-invasive bladder cancer (MIBC). However, rates and appropriateness of perioperative chemotherapy utilization remain unclear. We therefore sought to characterize use of perioperative chemotherapy in older radical cystectomy MIBC patients and examine factors associated with use., Methods: Using Surveillance, Epidemiology, and End Results (SEER)-Medicare data, we identified patients with MIBC diagnosed between 2004 and 2013 and treated with radical cystectomy. We classified patients into 3 treatment groups: cystectomy alone, neoadjuvant, or adjuvant chemotherapy. Chemotherapy was classified by regimen. We then fit a multinomial multivariable logistic regression model to assess association between patient factors with the receipt of each treatment., Results: We identified 3,826 eligible patients. The majority (484; 65%) received cystectomy alone. Neoadjuvant (676; 18% overall, 69% cisplatin-based), and adjuvant chemotherapy (666, 17% overall, 55% cisplatin-based) were used in similar proportions of cystectomy patients. Over the study period, the odds of receiving adjuvant chemotherapy decreased by 7.5%, whereas neoadjuvant therapy increased by 27.5% (both P < 0.001). There was an increase in use of cisplatin-based regimens in the neoadjuvant setting (35 to 72%, P < 0.001), but not the adjuvant setting. Female gender, lower comorbidity, married status, and lower stage disease were associated with greater odds of receiving neoadjuvant chemotherapy (all P < 0.05)., Conclusion: From 2004 to 2013 use of neoadjuvant chemotherapy for MIBC increased while use of adjuvant chemotherapy decreased. Future studies examining barriers to appropriate chemotherapy use, and the comparative effectiveness of neoadjuvant versus adjuvant chemotherapy are warranted., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Breast cancer subtype is a key determinant in treatment decision-making, and also effects survival outcome. In this population-based study, in-depth analyses were performed to examine the impact that breast cancer subtype and receipt of guideline-concordant adjuvant systemic therapy (AST) have on survival using a population-based cancer registry's data., Methods: Women aged ≥20 years with microscopically confirmed stage I-III breast cancer diagnosed in 2011 were identified from the Louisiana Tumor Registry. Breast cancer subtypes were categorized based on hormone receptor (HR) and HER2 status. Guideline-concordant treatment was defined using the NCCN Guidelines for Breast Cancer. Logistic regression was applied to identify factors associated with guideline-concordant AST receipt. Kaplan-Meier survival curves were generated to compare survival among subtypes by AST receipt status, and a semiparametric additive hazard model was used to verify the factors impacting survival outcome., Results: Of 2,214 eligible patients, most (70.8%) were HR+/HER2- followed by HR-/HER2- (14.4%), and 78.6% received guideline-concordant AST. Compared with patients with the HR+/HER2+ subtype, women with other subtypes were more likely to be guideline-concordant after adjusting for sociodemographic and clinical variables. Women with the HR-/HER2+ or HR-/HER2- subtype had a higher risk of any-cause and breast cancer-specific death than those with the HR+/HER2+ subtype. Those who did not receive AST had an additional adjusted hazard of 0.0191 (P=.0001) in overall survival and 0.0126 (P=.0011) in cause-specific survival compared with those who received AST., Conclusions: Most patients received guideline-concordant AST, except for those with the HR+/HER2+ subtype. Patients receiving guideline-adherent adjuvant therapy had better survival outcomes across all breast cancer subtypes.

Background: For clinically appropriate early-stage breast cancer patients, reflex criteria for Oncotype DX ordering ("the intervention") were implemented at our comprehensive cancer center, which reduced time-to-adjuvant chemotherapy initiation. Our objective was to evaluate Oncotype DX ordering practices and chemotherapy use before and after implementation of the intervention., Materials and Methods: We examined medical records for 498 patients who had definitive breast cancer surgery at our center. The post-intervention cohort consisted of 232 consecutive patients who had Oncotype DX testing after reflex criteria implementation. This group was compared to a retrospective cohort of 266 patients who were diagnosed and treated prior to reflex criteria implementation, including patients who did and did not have Oncotype DX ordered. Factors associated with Oncotype DX ordering pre- and post-intervention were examined. We used multivariate logistic regression to evaluate factors associated with chemotherapy receipt among patients with Oncotype DX testing., Results: The distribution of Oncotype DX scores, the proportion of those having Oncotype DX testing (28.9% vs. 34.1%) and those receiving chemotherapy (14.3% vs. 19.4%), did not significantly change between pre- and post-intervention groups. Age ≤65 years, stage II, grade 2, 1-3+ nodes, and tumor size >2 cm were associated with higher odds of Oncotype DX testing. Among patients having Oncotype DX testing, node status and Oncotype DX scores were significantly associated with chemotherapy receipt., Conclusion: Our criteria for reflex Oncotype DX ordering appropriately targeted patients for whom Oncotype DX would typically be ordered by providers. No significant change in the rate of Oncotype DX ordering or chemotherapy use was observed after reflex testing implementation., Implications for Practice: This study demonstrates that implementing multidisciplinary consensus reflex criteria for Oncotype DX ordering maintains a stable Oncotype DX ordering rate and chemotherapy rate, mirroring what was observed in a specific clinical practice, while decreasing treatment delays due to additional testing. These reflex criteria appropriately capture patients who would likely have had Oncotype DX ordered by their providers and for whom the test results are predicted to influence management. This intervention serves as a potential model for other large integrated, multidisciplinary oncology centers to institute processes targeting patient populations most likely to benefit from genomic assay testing, while mitigating treatment delays., Competing Interests: Disclosures of potential conflicts of interest may be found at the end of this article., (© AlphaMed Press 2018.)

Purpose: To develop an evidence-based clinical practice guideline to assist in clinical decision making for patients with resected biliary tract cancer., Methods: ASCO convened an Expert Panel to conduct a systematic review of the literature on adjuvant therapy for resected biliary tract cancer and provide recommended care options for this patient population., Results: Three phase III randomized controlled trials, one phase II trial, and 16 retrospective studies met the inclusion criteria., Recommendations: Based on evidence from a phase III randomized controlled trial, patients with resected biliary tract cancer should be offered adjuvant capecitabine chemotherapy for a duration of 6 months. The dosing used in this trial is described in the qualifying statements, while it should be noted that the dose of capecitabine may also be determined by institutional and regional practices. Patients with extrahepatic cholangiocarcinoma or gallbladder cancer and a microscopically positive surgical resection margin (R1 resection) may be offered chemoradiation therapy. A shared decision-making approach is recommended, considering the risk of harm and potential for benefit associated with radiation therapy for patients with extrahepatic cholangiocarcinoma or gallbladder cancer. Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines .

Background: Postoperative adjuvant chemotherapy with S-1 for 1 year (corresponding to eight courses) is standard care for stage II gastric cancer. Whether the duration of S-1 could be shortened to 6 months (corresponding to four courses) without worsening survival is unclear. The aim of this study was to investigate the non-inferiority of four courses of S-1 compared with eight courses of S-1 for patients with stage II gastric cancer., Methods: We did a phase 3, open-label, randomised controlled, non-inferiority trial at 59 hospitals in Japan. Patients aged 20-80 years with stage II adenocarcinoma of the stomach were randomly assigned (1:1) to eight courses or four courses of S-1. Randomisation was done by the Japan Clinical Oncology Group Data Center website, using a minimisation method with a random component using institution, stage (IIA vs IIB), age (<70 years vs ≥70 years), and mode of operation (open gastrectomy with bursectomy vs open gastrectomy without bursectomy vs laparoscopic gastrectomy) as adjustment factors. One course was 80 mg/day per m 2 of S-1 administered for 4 weeks followed by a rest for 2 weeks. The primary endpoint was relapse-free survival, analysed by intention to treat, with a non-inferiority margin for the hazard ratio (HR) set at 1·37. This study is registered at UMIN-Clinical Trial Registry, number UMIN000007306., Findings: Between Feb 16, 2012, and March 19, 2017, 590 patients were enrolled (295 per group). 528 (89%) patients were analysed at the first planned interim analysis in March, 2017, at which time the point estimate of HR for the four-course group compared with the eight-course group was 2·52 (95% CI 1·11-5·77), which exceeded 1·37 and met the prespecified criteria for early termination. Predictive probability for showing non-inferiority at the final analysis was calculated to be 2·9%. The study was stopped for futility. Updated 3-year relapse-free survival analysed in May, 2017, was 93·1% (95% CI 87·8-96·1) for the eight-course group and 89·8% (84·2-93·5) for the four-course group (HR 1·84, 95% CI 0·93-3·63). The most common grade 3-4 adverse event was neutropenia, observed in 46 (16%) patients in the eight-course group and 51 (17%) patients in the four-course group., Interpretation: S-1 for 1 year should remain as standard adjuvant chemotherapy for stage II gastric cancer., Funding: Japan Agency for Medical Research and Development; the Ministry of Health, Labour and Welfare of Japan; the National Cancer Center Research and Development Fund, Japan., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: In this study we present historic data on adherence to and survival outcomes associated with recently introduced quality measures for the management of non-small-cell lung cancer., Methods: The National Cancer Data Base was queried to identify all patients with non-small-cell lung cancer from 1998 to 2011. Adherence to guidelines was assessed for each of 3 Commission on Cancer-defined quality measures: (1) sampling 10 regional lymph nodes at surgery; (2a) surgery within 120 days of neoadjuvant chemotherapy or, (2b) 180 days of adjuvant chemotherapy; and (3) nonsurgical primary therapy in cN2 disease. The likelihood of measure adherence and the association of measure adherence with all-cause mortality were analyzed controlling for patient, hospital, and time period characteristics., Results: Regional lymph node sampling was inadequate in 72.7% of cases. Only 28.7% began adjuvant chemotherapy within 180 days of surgery. However, 96.5% of patients who received neoadjuvant chemotherapy proceeded to surgery within 120 days and surgery was first-line treatment for cN2 disease in only 3.7% of patients. Uninsured or Medicaid status was an independent risk factor for a prolonged delay between neoadjuvant chemotherapy and surgery (odds ratio, 1.36; 95% confidence interval, 1.08-1.72) and surgery and adjuvant treatment (odds ratio, 1.92; 95% confidence interval, 1.69-2.19). Overall survival was significantly better in patients whose care conformed to quality standards for nodal sampling (measure 1), and timing of chemotherapy., Conclusions: Adherence rates for nodal sampling at the time of surgery and receipt of adjuvant chemotherapy were low. These findings highlight opportunities for improvement efforts, but more measures are needed to more broadly assess the quality of lung cancer care., (Copyright © 2018. Published by Elsevier Inc.)