Focused ultrasound and concurrent chemotherapy for the treatment of advanced pancreatic cancer: A systematic review.

BACKGROUND AND OBJECTIVES: The combination of focused ultrasound (FUS) and chemotherapy is a novel treatment for pancreatic cancer. This paper reviews the literature on this combined therapy. METHODS: The medical literature was searched according to PRISMA guidelines. Inclusion criteria were any study of patients with pancreatic cancer undergoing treatment with FUS and chemotherapy. Data extracted included stage, radiologic response, resection rate, survival, and adverse events. RESULTS: The initial search yielded 212 citations; 10 studies met inclusion criteria (9 retrospective cohorts; 1 randomized trial). A total of 631 patients received FUS + chemotherapy; 63.6% being stage 4, and 29.7% stage 3. Patient selection, FUS parameters, and chemotherapy used were all heterogeneous. Overall survival ranged from 7.4 to 21.6 months, radiologic response rate was 44.1%, and 24.4% of stage 3 patients underwent resection. All four studies with a comparison group demonstrated improved survival. FUS + chemotherapy decreased pain in 69.7% of patients. Severe adverse events occurred in 0.65%. CONCLUSIONS: The literature on combined FUS and chemotherapy for pancreatic cancer is heterogeneous. There is good evidence that adverse events are low, and that it provides effective palliation. There is evidence to suggest oncologic benefit, however, this is subject to selection bias and prospective trials are needed.

Addressing the Rising Trend in Early-Age-Onset Cancers in Canada.

A multi-disciplinary symposium on early-age onset cancer (EAOC) was held in October 2023 to explore challenges experienced by this rapidly growing population. A major outcome of the symposium was recognition of the remarkable similarities of EAOC patients' journeys across cancer sites. Prevention and early detection of cancer are hindered by a lack of awareness among patients and family doctors that cancer can and does occur in younger persons. Distinct characteristics of the disease-such as a later stage at diagnosis and more aggressive tumor biology-require more potent treatments, which result in profound physical and psychosocial consequences that are unique to this age group. EAOC patient empowerment emerged as another key theme of the symposium. The development of a greater number of specialized clinics was called for, and patient support groups were recognized for the vital role they play in empowering patients and their families. Leading-edge medical advancements hold tremendous hope across the spectrum of EAOC care. New technologies based on genomic profiling, immunotherapy and microbiome alteration contribute to the development of highly effective, personalized approaches to treatment. All symposium participants expressed their commitment to speak with one resounding voice to advocate for equitable access to leading care practices for EAOC patients; thus, a fourth symposium is planned for November 2024.

Barriers and Unequal Access to Timely Molecular Testing Results: Addressing the Inequities in Cancer Care Delays across Canada.

Genomic medicine is a powerful tool to improve diagnosis and outcomes for cancer patients by facilitating the delivery of the right drug at the right dose at the right time for the right patient. In 2023, a Canadian conference brought together leaders with expertise in different tumor types. The objective was to identify challenges and opportunities for change in terms of equitable and timely access to biomarker testing and reporting at the education, delivery, laboratory, patient, and health-system levels in Canada. Challenges identified included: limited patient and clinician awareness of genomic medicine options with need for formal education strategies; failure by clinicians to discuss genomic medicine with patients; delays in or no access to hereditary testing; lack of timely reporting of results; intra- and inter-provincial disparities in access; lack of funding for patients to access testing and for laboratories to provide testing; lack of standardized testing; and impact of social determinants of health. Canada must standardize its approach to biomarker testing across the country, with a view to addressing current inequities, and prioritize access to advanced molecular testing to ensure systems are in place to quickly bring innovation and evidence-based treatments to Canadian cancer patients, regardless of their place of residence or socioeconomic status.

Developing DPYD Genotyping Method for Personalized Fluoropyrimidines Therapy.

BACKGROUND: Fluoropyrimidine drugs are widely used in chemotherapy to treat solid tumors. However, severe toxicity has been reported in 10% to 40% of patients. The DPYD gene encodes the rate-limiting enzyme dihydropyrimidine dehydrogenase responsible for fluoropyrimidine catabolism. The DPYD variants resulting in decreased or no enzyme activity are associated with increased risk of fluoropyrimidine toxicity. This study aims to develop a pharmacogenetic test for screening DPYD variants to guide fluoropyrimidine therapy. METHODS: A multiplex allele-specific polymerase chain reaction (AS-PCR) assay, followed by capillary electrophoresis, was developed to detect 5 common DPYD variants (c.557A > G, c.1129-5923C > G, c.1679T > G, c.1905 + 1G > A, and c.2846A > T). Deidentified population samples were used for screening positive controls and optimizing assay conditions. Proficiency testing samples with known genotypes were analyzed for test validation. All variants detected were confirmed by Sanger sequencing. RESULTS: From the deidentified population samples, 5 samples were heterozygous for c.557A > G, 2 samples were heterozygous for c.1129-5923C > G (HapB3), and 1 sample was heterozygous for c.2846A > T. The 20 proficiency samples matched with their assigned genotypes, including 13 wild-type samples, 3 samples heterozygous for c.1679T > G, 2 samples heterozygous for c.1905 + 1G > A, and 2 samples heterozygous for c.2846A > T. One of the 3 patient samples was heterozygous for c.1129-5923C > G (HapB3). All the variants detected by the multiplex AS-PCR assay were concordant with Sanger sequencing results. CONCLUSIONS: A robust multiplex AS-PCR assay was developed to rapidly detect 5 variants in the DPYD gene. It can be used for screening DPYD variants to identify patients with increased risk of toxicity when prescribed fluoropyrimidine therapy.

Breaking Down Barriers to Detection and Care in Early-Age-Onset Colorectal Cancer in Canada.

The second Early-Age-Onset Colorectal Cancer Symposium, convened in October 2022, sought solutions to the barriers to early detection and care for colorectal cancer in Canada. This meeting built on a previous symposium, held in 2021 and reported in this journal. Early-age-onset colorectal cancer (EAOCRC) affects increasing numbers of people under the age of 50 in Canada and throughout the developed world. Two main themes emerged from the meeting: the importance of timely detection, and the need for a tailored approach to the care of EAOCRC. Early detection is crucial, especially in light of the later stage at diagnosis and unique tumour characteristics. Symposium participants were strongly in favour of reducing the age of eligibility for screening from 50 to 45, and promoting the development of non-invasive screening techniques such as testing for circulating tumour DNA and biomarkers. Leading approaches to care were described and discussed, which meet the unique treatment needs of younger CRC patients. Multidisciplinary practices within and outside Canada address such factors as fertility, family roles, education, careers and financial responsibilities. These models can be applied in treatment centres across the country.

Mortality among patients with diffuse large B-cell lymphoma and mental disorders: a population-based study.

BACKGROUND: Mental disorders have been reported in patients with diffuse large B-cell lymphoma (DLBCL), but studies examining their association with mortality are lacking. METHODS: We conducted a population-based study using linked administrative health-care databases from Ontario, Canada. All patients with DLBCL 18 years of age or older treated with rituximab-based therapy between January 1, 2005, and December 31, 2017, were identified and followed until March 1, 2020. Mental disorders were defined as either preexisting or postdiagnosis (after lymphoma treatment initiation). Cox proportional hazards models were used to estimate the adjusted hazard ratio (HR) between mental disorders and 1-year and all-cause mortality while controlling for covariates. RESULTS: We identified 10 299 patients with DLBCL. The median age of the cohort was 67 years; 46% of patients were female, and 28% had a preexisting mental disorder. At 1-year follow-up, 892 (9%) had a postdiagnosis mental disorder, and a total of 2008 (20%) patients died. Preexisting mental disorders were not associated with 1-year mortality (adjusted HR = 1.06, 95% confidence interval [CI] = 0.96 to 1.17, P = .25), but postdiagnosis disorders were (adjusted HR = 1.51, 95% CI = 1.26 to 1.82, P = .0001). During a median follow-up of 5.2 years, 2111 (22%) patients had a postdiagnosis mental disorder, and 4084 (40%) patients died. Both preexisting and postdiagnosis mental disorders were associated with worse all-cause mortality (preexisting adjusted HR = 1.12, 95% CI = 1.04 to 1.20, P = .0024; postdiagnosis adjusted HR = 1.63, 95% CI = 1.49 to 1.79, P < .0001). CONCLUSIONS: Patients with DLBCL and mental disorders had worse short-term and long-term mortality, particularly those with postdiagnosis mental disorders. Further studies are needed to examine mental health service utilization and factors mediating the relationship between mental disorders and inferior mortality.

Do female and male patients derive similar benefits from approved systemic oncology therapies? A systematic review and meta-analysis.

PURPOSE: The National Institutes of Health's policy for the inclusion of females in clinical research was a pivotal step towards the consideration of sex as a biological variable, which is of particular importance in oncology, given differential incidence and outcomes of cancer between the sexes, and known pharmacodynamic, pharmacokinetic, and immunological differences. Therefore, we aim to investigate if such biological sex-based differences translate to clinically meaningful outcome differences from recently approved systemic oncology therapies. METHODS: A systematic review of randomized control trials (RCTs) cited in Food and Drug Administration, European Medicines Agency, and Health Canada approvals was conducted. Chemotherapy, targeted agents, and immunotherapy RCTs reporting sex-based sub-group analyses for overall/progression-free survival (OS/PFS) were considered. Hazard ratios (HRs) and 95% confidence intervals (CIs) were utilized. Sensitivity analyses for survival endpoints, drug type, and cancer site were conducted. RESULTS: Ninety-nine RCTs were included, representing 62,384 patients (23,574 (38%) female). Pooled OS HRs [95% CIs] were 0.77 [0.72-0.81] and 0.76 [0.72-0.79] for females and males, respectively (P = 0.73), and 0.51 [0.47-0.56] and 0.57 [0.53-0.61] (P = 0.08) for PFS. Sensitivity analyses yielded similar results. No RCTs reported sex-based toxicity or quality-of-life (QOL) data. CONCLUSION: Female and male patients appear to derive comparable benefits from recently approved systemic oncology therapies. Future RCTs are encouraged to report sex-based toxicity and QOL data.

Erythroblastic oncogene B-2 status and intracranial metastatic disease in patients with gastrointestinal cancer: a systematic review.

PURPOSE: The incidence of intracranial metastatic disease (IMD) in patients with gastrointestinal (GI) cancers is rising. Expression of the erythroblastic oncogene B-2 (ERBB2) is associated with an in increased risk of IMD in patients with breast cancer. The implications of ERBB2 expression for IMD risk in patients with GI cancers is less clear. The objective of this systematic review was to determine the incidence of IMD and OS in patients with ERBB2+ gastrointestinal cancers. METHODS: A literature search of MEDLINE, EMBASE, CENTRAL, and grey literature sources was conducted from date of database inception to July 2021. Included studies reported outcomes on patients with IMD secondary to ERBB2 GI cancers. RESULTS: Fourteen cohort studies met inclusion criteria, of which thirteen were retrospective. Eleven studies reported on gastric, esophageal, or gastroesophageal junction cancers. Three studies directly compared incidence of IMD based on ERBB2 status and among these, ERBB2+ patients had a higher incidence of IMD. One study indicated that ERBB2+ patients had significantly longer OS from the times of primary cancer (P = .015) and IMD diagnosis (P = .01), compared with patients with ERBB2- disease. CONCLUSIONS: In this systematic review, patients with ERBB2+ GI cancer were more likely to develop IMD. Future study is required on the prognostic and predictive value of ERBB2 status in patients with GI cancers.

Comparison of Use of Neoadjuvant Systemic Treatment for Breast Cancer and Short-term Outcomes Before vs During the COVID-19 Era in Ontario, Canada.

Importance: In response to an increase in COVID-19 infection rates in Ontario, several systemic treatment (ST) regimens delivered in the adjuvant setting for breast cancer were temporarily permitted for neoadjuvant-intent to defer nonurgent breast cancer surgical procedures. Objective: To examine the use and compare short-term outcomes of neoadjuvant-intent vs adjuvant ST in the COVID-19 era compared with the pre-COVID-19 era. Design, Setting, and Participants: This was a retrospective population-based cohort study in Ontario, Canada. Patients with cancer starting selected ST regimens in the COVID-19 era (March 11, 2020, to September 30, 2020) were compared to those in the pre-COVID-19 era (March 11, 2019, to March 10, 2020). Patients were diagnosed with breast cancer within 6 months of starting systemic therapy. Main Outcomes and Measures: Estimates were calculated for the use of neoadjuvant vs adjuvant ST, the likelihood of receiving a surgical procedure, the rate of emergency department visits, hospital admissions, COVID-19 infections, and all-cause mortality between treatment groups over time. Results: Among a total of 10 920 patients included, 7990 (73.2%) started treatment in the pre-COVID-19 era and 7344 (67.3%) received adjuvant ST; the mean (SD) age was 61.6 (13.1) years. Neoadjuvant-intent ST was more common in the COVID-19 era (1404 of 2930 patients [47.9%]) than the pre-COVID-19 era (2172 of 7990 patients [27.2%]), with an odds ratio of 2.46 (95% CI, 2.26-2.69; P < .001). This trend was consistent across a range of ST regimens, but differed according to patient age and geography. The likelihood of receiving surgery following neoadjuvant-intent chemotherapy was similar in the COVID-19 era compared with the pre-COVID-19 era (log-rank P = .06). However, patients with breast cancer receiving neoadjuvant-intent hormonal therapy were significantly more likely to receive surgery in the COVID-19 era (log-rank P < .001). After adjustment, there were no significant changes in the rate of emergency department visits over time between patients receiving neoadjuvant ST, adjuvant ST, or ST only during the ST treatment period or postoperative period. Hospital admissions decreased in the COVID-19 era for patients who received neoadjuvant ST compared with adjuvant ST or ST alone (P for interaction = .01 for both) in either setting. Conclusions and Relevance: In this cohort study, patients were more likely to start neoadjuvant ST in the COVID-19 era, which varied across the province and by indication. There was limited evidence to suggest any substantial impact on short-term outcomes.

Regional Therapy for Colorectal Cancer Liver Metastases: Which Modality and When?

For patients with unresectable colorectal liver metastases (uCRLM), regional therapies leverage the unique, dual blood supply to the liver; the hepatic artery is the main blood supply for liver tumors, whereas the portal vein supplies most normal hepatic parenchyma. Infusion of cancer therapies via the hepatic artery allows selective delivery to the tumors with relative sparing of normal liver tissue and little extrahepatic exposure, thus limiting systemic side effects. There is a paucity of randomized controlled trial evidence to inform the optimal integration of regional therapies into the management of CRLM. Hepatic arterial infusion pump (HAIP) chemotherapy has a potential survival benefit when used in the adjuvant setting after resection of CRLM. HAIP chemotherapy can be safely given with contemporary systemic therapies and is associated with a high objective response and rate of conversion to resectability in patients with uCRLM. Drug-eluting beads coated with irinotecan transarterial chemoembolization is associated with high objective response rates within the liver and has a well-established safety profile in patients with uCRLM. Transarterial radioembolization achieves high rates of response within the liver but is not associated with improvements in overall survival or quality of life in the first- or second-line setting for uCRLM. The best treatment approach is the one that most aligns with a given patients' values, preferences, and philosophy of care. In the first-line setting, HAIP could be offered to motivated patients who hope to achieve conversion to resectability. After progression on chemotherapy, HAIP, transarterial chemoembolization, and transarterial radioembolization are valuable treatment options to consider for patients with liver-limited or liver-predominant CRLM who seek to optimize response rates and regional control.

Real-World Cost-Effectiveness of First-Line Gemcitabine Plus Nab-Paclitaxel vs FOLFIRINOX in Patients With Advanced Pancreatic Cancer.

BACKGROUND: There are no randomized control trials (RCTs) comparing gemcitabine and nab-paclitaxel (Gem-Nab) and fluorouracil, folinic acid, irinotecan, oxaliplatin (FOLFIRINOX) for advanced pancreatic cancer (APC). Although it is well known that RCT-based efficacy often does not translate to real-world effectiveness, there is limited literature investigating comparative cost-effectiveness of Gem-Nab vs FOLFIRINOX for APC. We aimed to examine the real-world cost-effectiveness of Gem-Nab vs FOLFIRINOX for APC in Ontario, Canada. METHODS: This study compared patients treated with first-line Gem-Nab or FOLFIRINOX for APC in Ontario from April 2015 to March 2019. Patients were linked to administrative databases. Using propensity scores and a stabilizing weights method, an inverse probability of treatment weighted cohort was developed. Mean survival and total costs were calculated over a 5-year time horizon, adjusted for censoring, and discounted at 1.5%. Incremental cost-effectiveness ratio and net monetary benefit were computed to estimate cost-effectiveness from the public health-care payer's perspective. Sensitivity analysis was conducted using the propensity score matching method. RESULTS: A total of 1988 patients were identified (Gem-Nab: n = 928; FOLFIRINOX: n = 1060). Mean survival was lower for patients in the Gem-Nab than the FOLFIRINOX group (0.98 vs 1.26 life-years; incremental effectiveness = -0.28 life-years [95% confidence interval = -0.47 to -0.13]). Patients in the Gem-Nab group incurred greater mean 5-year total costs (Gem-Nab: $103 884; FOLFIRINOX: $101 518). Key cost contributors include ambulatory cancer care, acute inpatient hospitalization, and systemic therapy drug acquisition. Gem-Nab was dominated by FOLFIRINOX, as it was less effective and more costly. Results from the sensitivity analysis were similar. CONCLUSIONS: Gem-Nab is likely more costly and less effective than FOLFIRINOX and therefore not considered cost-effective at commonly accepted willingness-to-pay thresholds.

An Evaluation of Sex- and Gender-Based Analyses in Oncology Clinical Trials.

BACKGROUND: The objective of this study was to evaluate whether sex- and gender-based analyses and proper sex and gender terminology were used in oncology trials leading to regulatory drug approval. METHODS: The Food and Drug Administration (FDA) Hematology/Oncology Approvals and Safety Notifications page was used to identify all anticancer therapies that received FDA approval between 2012 and 2019. The trials used to support FDA drug approval were collected along with all available supplemental tables and study protocols. Documents were reviewed to determine if there was a plan to analyze results according to sex and gender and to determine if consistent sex and gender terminology were used. RESULTS: We identified 128 randomized, controlled trials corresponding to a cancer medicine, which received FDA approval. No study specified how sex and gender were collected or analyzed. No study reported any information on the gender of participants. Sex and gender terminology were used inconsistently at least once in 76% (97 of 128) of studies. Among the 102 trials for nonsex-specific cancer sites, 89% (91 of 102) presented disaggregated survival outcome data by sex. No study presented disaggregated toxicity data by sex or gender. CONCLUSION: The majority of pivotal clinical trials in oncology fail to account for the important distinction between sex and gender and conflate sex and gender terminology. More rigor in designing clinical trials to include sex- and gender-based analyses and more care in using sex and gender terms in the cancer literature are needed. These efforts are essential to improve the reproducibility, generalizability, and inclusiveness of cancer research.

Small Particle DEBIRI TACE as Salvage Therapy in Patients with Liver Dominant Colorectal Cancer Metastasis: Retrospective Analysis of Safety and Outcomes.

The aim of this study was to examine the safety and efficacy of 40 µm and 75 µm calibrated irinotecan-eluting beads (DEBIRI-TACE) for the treatment of colorectal cancer metastases. We conducted a retrospective review of 36 patients with unresectable liver metastases from colorectal cancer who were treated with DEBIRI-TACE between 2017 to 2020. Patients who received at least one session of DEBIRI were included in our analysis. A total of 105 DEBIRI sessions were completed. 86% of patients (n = 31) underwent one round of treatment, 14% of patients (n = 5) underwent two distinct rounds of treatment. The majority of patients were discharged the next day (92%, n = 33 patients) with no 30-day post-DEBIRI mortality. Five high-grade adverse events occurred, including longer stay for pain management (n = 2), postembolization syndrome requiring readmission (n = 2), and liver abscess (n = 1). The average survival from diagnosis of metastatic disease was 33.3 months (range 11-95, median 28). Nine of 36 patients are still alive (December 2020) and have an average follow-up time of 36.8 months from T0 (range 12-63, median 39). Small particle DEBIRI is safe and well-tolerated in the salvage setting, with outcomes comparable to that of larger bead sizes.

The Association of Drug-Funding Reimbursement With Survival Outcomes and Use of New Systemic Therapies Among Patients With Advanced Pancreatic Cancer.

Importance: Gemcitabine-nab-paclitaxel (GEMNAB) and fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) both improve survival of patients with advanced pancreatic cancer when compared with single-agent gemcitabine in clinical trials. Objective: To describe changes in the survival of patients with advanced pancreatic cancer associated with sequential drug-funding approvals and to determine if there exist distinct patient populations for whom GEMNAB and FOLFIRINOX are associated with survival benefit. Design, Setting, and Participants: This population-based, retrospective cohort study examined all incident cases of advanced pancreatic cancer treated with first-line chemotherapy in Ontario, Canada (2008-2018) that were identified from the Cancer Care Ontario (Ontario Health) New Drug Funding Program database. Statistical analysis was performed from October 2020 to January 2021. Exposures: First-line chemotherapy for advanced pancreatic cancer. Main Outcomes and Measures: The main outcomes were the proportion of patients treated with each chemotherapy regimen over time and overall survival for each regimen. Cox proportional hazards regression models were used to compare overall survival between treatment regimens after adjustment for confounding variables, inverse probability of treatment weighting, and matching. Results: From 2008 to 2018, 5465 patients with advanced pancreatic cancer were treated with first-line chemotherapy in Ontario, Canada. The median (range) age of patients was 66.9 (27.8-93.4) years; 2447 (45%) were female; 878 (16%) had prior pancreatic resection, and 328 (6%) had prior adjuvant gemcitabine. During the time period when only gemcitabine and FOLFIRINOX were funded (2011-2015), 49% (929 of 1887) received FOLFIRINOX. When GEMNAB was subsequently funded (2015-2018), 9% (206 of 2347) received gemcitabine, 44% (1034 of 2347) received FOLFIRINOX, and 47% (1107 of 2347) received GEMNAB. The median overall survival increased from 5.6 months (95% CI, 5.1-6.0 months) in 2008 to 2011 to 6.9 months (95% CI, 6.5-7.4 months) in 2011 to 2015 to 7.6 months (95% CI, 7.1-8.0 months) in 2015 to 2018. Patients receiving FOLFIRINOX were younger and healthier than patients receiving GEMNAB. After adjustment and weighting, FOLFIRINOX was associated with better overall survival than GEMNAB (hazard ratio [HR], 0.75 [95% CI, 0.69-0.81]). In analyses comparing patients treated with GEMNAB and gemcitabine, GEMNAB was associated with better overall survival (HR, 0.86 [95% CI, 0.78-0.94]). Conclusions and Relevance: This cohort study of patients with advanced pancreatic cancer receiving first-line palliative chemotherapy within a universal health care system found that drug funding decisions were associated with increased uptake of new treatment options over time and improved survival. Both FOLFIRINOX and GEMNAB were associated with survival benefits in distinct patient populations.

A Rare Case of Small Bowel Extramedullary Plasmacytomas Presenting With Intestinal Obstruction.

Extramedullary plasmacytoma (EMP) is a plasma cell disorder involving soft tissues in the absence of clonal bone marrow involvement or destructive bone lesions. When present in the gastrointestinal (GI) tract, and specifically the small intestine, it can cause a wide range of symptoms including GI bleeding, obstruction, and abdominal pain. The diagnosis is challenging, as it can hold an indolent course, and is infrequently encountered in clinical practice. Diagnosis requires biopsy of the involved organ, which can be obtained during surgery or endoscopy, and other workup to rule out systemic disease and bone marrow involvement. Treatment depends on the primary site of disease involvement and the presence of other features of systemic disease. We report a case of multiple small bowel plasmacytomas in a 51-year-old female who presented with small bowel obstruction. She eventually underwent surgical resection and is currently on chemotherapy awaiting stem cell transplant.

Mental Health Resource Use Among Patients Undergoing Curative Intent Treatment for Bladder Cancer.

BACKGROUND: Patients with bladder cancer may experience mental health distress. Mental health-care service (MHS) use can quantify the magnitude of the problem. METHODS: The Ontario Cancer Registry was used to identify all patients with bladder cancer treated with curative-intent cystectomy or radiotherapy in Ontario, Canada (2004-2013). Population-level databases were used to identify MHS use (visits to general practitioner, psychiatrist, emergency department, or hospitalization). Generalized estimating equations were used to compare rates of MHS use. Baseline, peritreatment, and posttreatment MHS use were defined as visits from 2 years to 3 months before, 3 months before to 3 months after, and from 3 months after to 2 years after start of treatment, respectively. RESULTS: From 2004 to 2013, 4296 patients underwent cystectomy (n = 3332) or curative-intent radiotherapy (n = 964). Compared with baseline, the rate of MHS use was higher in the peritreatment (adjusted rate ratio [aRR] = 1.64, 95% confidence interval [CI] = 1.48 to 1.82) and posttreatment periods (aRR = 1.45, 95% CI =1.30 to 1.63). By 2 years posttreatment, 24.6% (95% CI = 23.4% to 25.9%) of all patients had MHS use. Patients with baseline MHS use had substantially higher MHS use in the peritreatment (aRR = 5.77, 95% CI = 4.86 to 6.86) and posttreatment periods (aRR = 4.58, 95% CI = 3.78 to 5.55). Female patients had higher use MHS use overall, but males had a higher incremental increase in the posttreatment period compared with baseline (2-sided Pinteraction = .02). Male patients had a statistically significant increase in MHS use following surgery or radiotherapy, whereas female patients only had an increase following surgery. CONCLUSIONS: MHS use is common among patients undergoing treatment for bladder cancer, particularly in the peritreatment period. Screening for mental health concerns in this population is warranted.

Asymptomatic Ileal Neuroendocrine "Carcinoid" Tumor Incidentally Diagnosed on Colorectal Cancer Screening Colonoscopy: Does Routine TI Intubation Matter?

Gastrointestinal neuroendocrine tumors (GINETs) (also known as "carcinoids") are rare tumors with reported incidence of up to 6.98 per 100,000 which has increased significantly due to the increased detection on imaging and endoscopy. They are most commonly located in the small bowel, particularly the terminal ileum. Patients with small bowel NETs may present with abdominal pain, diarrhea, or carcinoid syndrome. However, the disease is mostly asymptomatic, and patients are usually diagnosed incidentally during routine colonoscopy. Although the ileum is the most common site for GINETs, terminal ileal (TI) intubation is not always completed during routine colonoscopy. With terminal ileum intubation being successful in at least 70% of colonoscopies and the rate of neuroendocrine tumor detection 0.1-1% of those intubations, one critical question remains unanswered: should terminal ileal intubation be considered a part of the definition of a complete colonoscopy? Herein, we present nine cases of NETs found incidentally on routine colon cancer screening colonoscopy in asymptomatic patients. This case series adds to the sparse literature and highlights the importance of TI intubation technique in early detection of small bowel NETs which could potentially affect the outcome.

Long-Term Mental Health Service Utilization Among Survivors of Testicular Cancer: A Population-Based Cohort Study.

PURPOSE: Testicular cancer survivors may experience mental illness as a consequence of their cancer diagnosis and treatment. METHODS: All incident cases of testicular cancer treated with orchiectomy in Ontario, Canada (2000-2010), were identified using the Ontario Cancer Registry. Cases were matched to controls in a 1:5 ratio on age and geography. Population-level databases were used to identify mental health service use episodes; outpatient use included visits to a general practitioner for a mental health concern or any visit to a psychiatrist. Negative binomial regression modeling was used to estimate the rate of mental health service use in the pretreatment (2 years prior until 1 month before orchiectomy), peritreatment (1 month before until 1 month after orchiectomy), and post-treatment periods (1 month after orchiectomy until end of follow-up). Rate ratios (RR) comparing cases with controls in the peri- and post-treatment periods were adjusted for baseline mental health service use. RESULTS: Two thousand six hundred nineteen cases of testicular cancer were matched to 13,095 controls. There was no baseline difference in the rate of mental health service use. Cases were significantly more likely than controls to have an outpatient visit for a mental health concern in the peritreatment (adjusted RR [aRR], 2.45; 95% CI, 2.06 to 2.92) and post-treatment periods (aRR, 1.30; 95% CI, 1.12 to 1.52). The difference in mental health service use persisted over a median follow-up of 12 years. In the postorchiectomy period, cases with baseline mental health service use were those most likely to use mental health services (aRR, 5.64; 95% CI, 4.64 to 6.85). CONCLUSION: Testicular cancer survivors use mental health services more often than healthy controls. Survivorship care plans that address the long-term mental healthcare needs of this population are needed.

Salvage Abdominoperineal Resection for Anal Squamous Cell Carcinoma: Use, Risk Factors, and Outcomes in a Canadian Population.

BACKGROUND: Previous studies have reported that 30% to 40% of patients with squamous cell carcinoma of the anus will require salvage abdominoperineal resection after chemoradiotherapy. OBJECTIVE: The purpose of this study was to identify the use, risk factors, and impact on survival of salvage abdominal perineal resection for squamous cell carcinoma of the anus. DESIGN: This was a retrospective, population-based cohort study. SETTINGS: Patients treated in Ontario, Canada through a single-payer universal healthcare system, were included. PATIENTS: Patients included all incident cases of squamous cell anal cancer who underwent curative intent radiotherapy from 2007 to 2015. MAIN OUTCOME MEASURES: Risk of salvage abdominoperineal resection, factors associated with salvage abdominoperineal resection, and survival were measured. RESULTS: A total of 1125 patients were treated with curative intent radiotherapy for squamous cell cancer of the anus. Within this cohort, salvage surgery was performed in 8% (93/1125), whereas 14% (156/1125) required a permanent colostomy. In log-binomial regression, younger age was associated with salvage surgery, whereas sex, cancer stage, socioeconomic status, and HIV were not. There was a suggested lower risk of salvage surgery in those who completed chemoradiation (relative risk = 0.67 (95% CI, 0.43-1.03)). Crude 5-year overall survival rate was 73% (95% CI, 70%-76%) in those not requiring salvage surgery and 48% (95% CI, 37%-58%) in those who did. In Cox models, mortality was higher in patients requiring salvage surgery compared with those who did not (adjusted HR = 2.20 (95% CI, 1.65-2.94), whereas improved survival was seen in those who completed chemoradiation (HR = 0.65 (95% CI, 0.42-0.82)) LIMITATIONS:: The study was limited by its potential residual confounding by indication for salvage surgery. CONCLUSIONS: In this large, contemporary cohort of patients with squamous cell carcinoma of the anus, the proportion of patients undergoing salvage surgery was considerably lower than previous reports. Younger age was associated with salvage surgery, and there was a suggestion of lower risk of salvage surgery with completion of chemoradiation. Patients requiring salvage surgery had poor 5-year overall survival. See Video Abstract at http://links.lww.com/DCR/B205. RAP DE RESCATE PARA EL CARCINOMA ANAL DE CéLULAS ESCAMOSAS: USO, FACTORES DE RIESGO Y RESULTADOS EN UNA POBLACIóN CANADIENSE: Estudios anteriores han reportado que 30-40% de los pacientes con carcinoma de células escamosas del ano requerirán una resección abdominoperineal de rescate después de la quimiorradioterapia.Identificar la utilización, los factores de riesgo y el impacto en la supervivencia de la resección abdominoperineal de rescate para el carcinoma de células escamosas del ano.Estudio de cohorte retrospectivo, basado en la población.Todos los casos incidentes de cáncer anal de células escamosas que se sometieron a radioterapia con fines curativos de 2007 a 2015.Pacientes tratados en Ontario, Canadá, un sistema de salud universal de un solo pagador.Riesgo de resección abdominoperineal de rescate, factores asociados con la resección abdominoperineal de rescate y la supervivencia.1125 pacientes fueron tratados con radioterapia de intención curativa para el cáncer de células escamosas del ano. Dentro de esta cohorte, la cirugía de rescate se realizó en el 8% (93/1125), mientras que el 14% (156/1125) requirió una colostomía permanente. En la regresión log-binomial, la edad más joven se asoció con la cirugía de rescate, mientras que el sexo, la etapa del cáncer, el estado socioeconómico y el VIH no. Se sugirió un menor riesgo de cirugía de rescate en aquellos que completaron la quimiorradiación (RR 0,67; IC del 95%: 0,43 a 1,03). La tasa de supervivencia global bruta a 5 años fue del 73% (IC del 95%: 70-76%) en aquellos que no requirieron cirugía de rescate y del 48% (IC del 95%: 37-58%) en los que sí lo requirieron. En los modelos de Cox, la mortalidad fue mayor en los pacientes que requirieron cirugía de rescate en comparación con aquellos que no lo requirieron (HR ajustado 2.20, IC 95%: 1.65 - 2.94), mientras que se observó una mejor supervivencia en aquellos que completaron la quimiorradiación (HR 0.65, IC 95% 0.42 - 0,82).Posible confusión residual por indicación de cirugía de rescate.En esta gran cohorte contemporánea de pacientes con carcinoma de células escamosas del ano, la proporción de pacientes sometidos a cirugía de rescate fue considerablemente menor que los informes anteriores. La edad más temprana se asoció con la cirugía de rescate, y se sugirió un menor riesgo de cirugía de rescate con la finalización de la quimiorradiación. Los pacientes que requirieron cirugía de rescate tuvieron una deficiente supervivencia general de 5 años. Consulte Video Resumen en http://links.lww.com/DCR/B205. (Traducción-Dr Gonzalo Hagerman).