Current Oncology

This review provides information regarding the preoperative examinations, indications for endoscopic resection (ER), and curability assessment in subjects with superficial esophageal squamous cell carcinoma (SCC). Narrow-band imaging (NBI) is a more sensitive modality for detecting esophageal cancer than conventional observation, and esophageal observation using NBI is thus recommended for the detection of superficial esophageal cancer. It is also important to adjust the volume of air in the esophagus during observation. Workup by non-magnifying followed by magnifying endoscopy is a common process for diagnosing the invasion depth of superficial esophageal SCCs in Japan. Endoscopic ultrasonography carries a risk of overdiagnosis, and its routine use is therefore not recommended. The Japanese endoscopic submucosal dissection/endoscopic mucosal resection guidelines for esophageal cancer considered the indications for ER based on the results of studies focusing on clinical MM/SM1 cancers, and concluded that clinical MM/SM1 carcinomas, except circumferential carcinoma, were an indication for ER. The curative effect of ER should be assessed based on histologic examination of the resected specimens. ER should be conducted based on a thorough understanding of the preoperative diagnosis, indication, curability, and additional treatment of esophageal SCC. Full article

Routine cervical cancer screening is important for women living with HIV (WLH) due to the greater incidence and persistence of high-risk HPV (HR-HPV) infection. HR-HPV self-sampling has been proposed to overcome barriers to in-office cervical cancer screening in underserved populations. However, little is known about baseline knowledge of HR-HPV and the acceptability of HR-HPV self-sampling among WLH. This paper describes WLH’s experiences and needs regarding cervical cancer screening, specifically HR-HPV self-sampling, and seeks to reconcile their experiences with the views of their providers. In total, 10 providers and 39 WLH participated in semi-structured interviews and group discussions, respectively. Knowledge of cervical cancer and HR-HPV was generally limited among WLH; when present, it was often due to personal experience of or proximity to someone affected by cervical cancer. Most WLH were not familiar with HR-HPV self-sampling but, despite some of the providers’ skepticism, expressed their willingness to participate in a mail-based HR-HPV self-sampling intervention and highlighted convenience, ease of use, and affordability as facilitators to the uptake of HR-HPV self-sampling. The experiences identified can be used to guide patient-centered communication aimed at improving cervical cancer knowledge and to inform interventions, such as HR-HPV self-sampling, designed to increase cervical cancer screening among under-screened WLH. Full article

The capecitabine/temozolomide regimen has significant activity in pancreatic NETs; however, data are limited in NETs of the small bowel (midgut). A retrospective study of all patients with metastatic midgut NETs seen at Moffitt Cancer Center between January 2008 and June 2019 treated with CAPTEM was conducted. 32 patients with proven or suspected well-differentiated primary small bowel NETs (excluding duodenum) were identified. 6 patients were found to have a radiographic response (19%), 5 of whom had high-grade disease. Only one patient among 23 with low/intermediate-grade disease responded (4%), whereas the response rate for patients with high-grade disease was 56%. Among patients with low/intermediate-grade disease, 44% discontinued due to poor tolerability. The CAPTEM regimen appears to have an activity in patients with high-grade small bowel NETs and is largely inactive in patients with low/intermediate-grade tumors. Full article

Background: 5-FU-based chemoradiotherapy (CRT) could be associated with severe treatment-related toxicities in patients harboring at-risk DPYD polymorphisms. Methods: The studied population included consecutive patients with locoregionally advanced oropharyngeal carcinoma treated with carboplatin and 5-FU-based CRT one year before and after the implementation of upfront DPYD*2A genotyping. We aimed to determine the effect of DPYD genotyping on grade ≥3 toxicities. Results: 181 patients were analyzed (87 patients before and 94 patients following DPYD*2A screening). Of the patients, 91% (n = 86) were prospectively genotyped for the DPYD*2A allele. Of those screened, 2% (n = 2/87) demonstrated a heterozygous DPYD*2A mutation. Extended genotyping of DPYD*2A-negative patients later allowed for the retrospective identification of six additional patients with alternative DPYD variants (two c.2846A>T and four c.1236G>A mutations). Grade ≥3 toxicities occurred in 71% of the patients before DPYD*2A screening versus 62% following upfront genotyping (p = 0.18). When retrospectively analyzing additional non-DPYD*2A variants, the relative risks for mucositis (RR 2.36 [1.39–2.13], p = 0.0063), dysphagia (RR 2.89 [1.20–5.11], p = 0.019), and aspiration pneumonia (RR 13 [2.42–61.5)], p = 0.00065) were all significantly increased. Conclusion: The DPYD*2A, c.2846A>T, and c.1236G>A polymorphisms are associated with an increased risk of grade ≥3 toxicity to 5-FU. Upfront DPYD genotyping can identify patients in whom 5-FU-related toxicity should be avoided. Full article

Cytomegalovirus (CMV) retinitis is a rare end-organ disease of CMV infection and is a marker of severe immunosuppression, especially in human immunodeficiency virus (HIV)-positive patients. In multiple myeloma (MM) patients, CMV retinitis has been reported in the post-transplant setting, with an incidence lower than 0.2%, and in patients receiving lenalidomide. Here, we describe the first case of CMV retinitis in myeloma patients following B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor T (BCMA CAR-T) cell therapy. In addition to CMV, the patient developed multiple infections including a mouth ulcer, pneumonia, and fungal enteritis. While the complete remission (CR) status of MM was maintained, he regained a visual acuity of 20/1000 after appropriate ophthalmologic treatment. This single case illustrates the potential of BCMA CAR-T therapy to induce profound humoral immunosuppression, and demonstrates an imperative need for an established standard of monitoring and prophylaxis of post-CAR-T infections. Full article

Targeting the immune system, especially the PDL-1/PD-1 axis, has significantly improved the outcomes of metastatic lung cancer patients. However, only a portion of patients will benefit significantly from PD(L)1 therapeutics alone or in combination with either chemotherapy or anti-CTLA4 antibody. It is therefore important to study predictive biomarkers to help select the patients who will experience the most benefit from immunotherapy. In this paper, the current status of PDL-1 expression on tumour cells, the smoking status of patients, tumour mutational burden, gut microbiome and STK11 and KEAP1 mutations in the tumour as predictive biomarkers for PD(L)-1-based immunotherapy are summarized. Full article

Objective: Given the increasing risk of young-onset colorectal cancer (yCRC) among adults under 50 years, it is important to understand impacts on reproductive health. Our objective was to assess experiences with reproductive health after yCRC diagnosis among females. Methods: We conducted a cross-sectional study among females, 18 years or older, who have been diagnosed yCRC and are able to communicate in English. Data were gathered using an online survey involving both quantitative (e.g., multiple choice) and qualitative (e.g., open-ended text) questions on pregnancy history, influence of yCRC on reproductive decisions, and experiences with reproductive healthcare. Results: Altogether, 101 females with yCRC participated, including 23 who had never been pregnant and 78 who had been pregnant. yCRC influenced family planning goals for one-third of participants. Furthermore, compared to participants who completed treatment, those currently undergoing treatment had higher odds of indicating their yCRC diagnosis influenced family planning goals (adjusted odds ratio 4.93; 95% confidence interval 1.29 to 18.78). Although 53 (52.5%) participants indicated having discussions regarding reproductive health with healthcare provider(s), 44 (43.6%) did not. Content analysis of open-ended survey questions identified themes on the emotional impacts, experiences with reproductive healthcare, reproductive and family planning considerations, and the related issue of sexual health impacts of yCRC. Conclusions: Gaps in care, related to limited reproductive health discussions, influence of yCRC on family planning, and experiencing lasting reproductive health impacts highlight the need for improving reproductive healthcare, particularly for females diagnosed with yCRC. Full article

Cancer treatment has evolved significantly over the past decade with the emergence of a multitude of new treatments across cancer types. Alongside the pace of drug discovery, the cost of cancer drugs has also increased. In the face of this growth in development and spending, it is crucial to have an understanding of the processes and pressures new drugs navigate to get to the market in Canada. This paper is a review of the complex, multi-step regulatory and funding process undertaken by cancer drugs in Canada. It reviews the role of Health Canada, the Patented Medicine Prices Review Board, the Health Technology Assessment, the pan-Canadian Pharmaceutical Alliance, and finally, the provincial, territorial, and federal payers. Recent developments are highlighted. Strategies to minimize duplication of effort, improve timeliness, and increase efficiency are explored. The cancer drug regulatory and funding process in Canada is complex, and an understanding of the current system and ongoing evolution is essential. Full article

Objective: To provide recommendations for preferred models of follow-up care for stage I-IV colorectal (CRC) cancer survivors in Ontario; to identify signs and symptoms of potential recurrence and when to investigate; and to evaluate patient information and support needs during the post-treatment survivorship period. Methods: Consistent with the Program in Evidence-Based Medicine’s standardized approach, MEDLINE, EMBASE, PubMed, Cochrane Library, and PROSPERO databases were systematically searched. The authors drafted recommendations and revised them based on the comments from internal and external reviewers. Results: Four guidelines, three systematic reviews, three randomized controlled trials, and three cohort studies provided evidence to develop recommendations. Conclusions: Colorectal cancer follow-up care is complex and requires multidisciplinary, coordinated care delivered by the cancer specialist, primary care provider, and allied health professionals. While there is limited evidence to support a shared care model for follow-up, this approach is deemed to be best suited to meet patient needs; however, the roles and responsibilities of care providers need to be clearly defined, and patients need to know when and how to contact them. Although there is insufficient evidence to recommend any individual or combination of signs or symptoms as strong predictor(s) of recurrence, patients should be educated about these and know which care provider to contact if they develop any new or concerning symptoms. Psychosocial support and empathetic, effective, and coordinated communication are most valued by patients for their post-treatment follow-up care. Continuing professional education should emphasize the importance of communication skills and coordination of communication between the patient, family, and healthcare providers. Full article

The risk of relapse for early breast cancer (BC) patients persists even after decades and to date, no specific and sensitive effective circulating biomarker for recurrence prediction has been identified yet. The international guidelines do not recommend the assessment of the serum tumor markers CEA and CA15-3 in the follow-up of asymptomatic early BC patients. In our institute, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, as part of the E.Pic.A study, which was designed to assess the economic appropriateness of integrated care pathways in early BC, the use of CEA and CA15-3 as circulating tumor biomarkers in early BC patients was evaluated in 1502 patients one year after surgery, from 2015 to 2018, with an overall expense of EUR 51,764. A total of EUR 47,780 (92%) was used for execution of circulating tumor markers in early BC patients with stage 0, I and II tumors, neglecting the current guidelines and considered inappropriate by our professional board. We found that no patients with stage I BC experienced relapse in the 365 days after surgery, and in any case examination of the circulating markers CEA and CA15-3 was considered crucial for diagnosis of relapse. Our findings suggest that this inadequacy is a low-value area, supporting the reallocation of economic resources for interventions of a higher value for patients. Full article

The prognostic value of the tumor growth rate (TGR) in huge hepatocellular carcinoma (HHCC) patients treated with transcatheter arterial chemoembolization (TACE) as an initial treatment remains unclear. This two-center retrospective study was conducted in 97 patients suffering from HHCC. Demographic characteristics, oncology characteristics, and some serological markers were collected for analysis. The TGR was significantly linear and associated with the risk of death when applied to restricted cubic splines. The optimal cut-off value of TGR was −8.6%/month, and patients were divided into two groups according to TGR. Kaplan–Meier analysis showed that the high-TGR group had a poorer prognosis. TGR (hazard ratio (HR), 2.06; 95% confidence interval (CI), 1.23–3.43; p = 0.006), presence of portal vein tumor thrombus (PVTT) (HR, 1.93; 95% CI, 1.13–3.27; p = 0.016), and subsequent combination therapy (HR, 0.59; 95% CI, 0.35–0.99; p = 0.047) were independent predictors of OS in the multivariate analysis. The model with TGR was superior to the model without TGR in the DCA analysis. Patients who underwent subsequent combination therapy showed a longer survival in the high-TGR group. This study demonstrated that higher TGR was associated with a worse prognosis in patients with HHCC. These findings will distinguish patients who demand more personalized combination therapy and rigorous surveillance. Full article

Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare and aggressive condition that is associated with the SMARCA4 mutation and has a dismal prognosis. It is generally diagnosed in young women. Here, we report a case of a young woman with SCCOHT harboring a rare molecular finding with a highly aggressive biological behavior. The patient had a somatic SMARCB1 mutation instead of an expected SMARCA4 alteration. Even though the patient was treated with high-dose chemotherapy followed by stem cell transplantation, she evolved with disease progression and died 11 months after her first symptoms appeared. We present a literature review of this rare disease and discuss the findings in the present patient in comparison to expected molecular alterations and options for SCCOHT treatment. Full article

Accelerated approval (AA) by the FDA enables earlier access to promising new therapies. Health Canada has a similar process. Canada implemented a national health technology assessment (HTA) for reimbursement decisions in 2011. This study evaluated regulatory and funding timelines and decisions for FDA AA cancer therapies in Canada. The FDA’s AA of malignant hematology and oncology from January 2000–December 2019 was reviewed. Dates from Health Canada, HTA decisions and provincial listings were collected. There were 94 FDA AAs, two of which were subsequently withdrawn. Of the 92 AAs, 70 received full (46)/conditional (24) Health Canada approval, and 22 were not filed. Since the introduction of HTA, 31 out of 45 of Health Canada’s approved indications underwent HTA review: 18 received a positive recommendation conditional on cost-effectiveness, 8 were not recommended and 5 were withdrawn/suspended. The median time from the AA to any Health Canada approval is 9.4 months, from any Health Canada approval to HTA decision is 5.8 months and from HTA decision to the first formulary listing is 12.0 months. The access and timeline for the first formulary listing differences were observed between the USA and Canada due to the decision of pharmaceutical companies to submit (or not) to regulatory/HTA bodies, national procedural delays with different healthcare delivery models and submission timelines. This study demonstrates that there is delayed access to promising new therapies in Canada. Full article

The surgical treatment of recurrent adenomas can be challenging. Intraoperative magnetic resonance imaging (iMRI) can improve the orientation and increase the safe extent of resection. We conducted a quantitative and qualitative retrospective analysis of recurrent adenomas treated by endoscopic or microscopic iMRI-assisted transsphenoidal surgery. A total number of 59 resections were selected. Detailed volumetric measurements, tumor characteristics, and MRI features of intraoperative remnants were evaluated. Intraoperative MRI increased the gross total resection (GTR) rate from 33.9% to 49.2%. Common locations of tumor remnants after iMRI were the clivus, the wall of the cavernous sinus or the perforation of the diaphragm. Increasing tumor volume and the microscopic technique were significantly associated with further resection after iMRI in the univariate analysis (p = 0.004, OR 1.6; p = 0.009, OR 4.4). Only the increasing tumor volume was an independent predictor for further resection (p = 0.007, OR 1.5). A significantly higher proportion of GTRs was achieved with the endoscopic technique (p = 0.001). Patients with a large recurrent pituitary adenoma who underwent microscopic transsphenoidal resection were the most likely to benefit from iMRI regarding the extent of resection. Occult invasions of the cavernous sinus and/or the clivus were the most common findings leading to further resection of tumor remnants after iMRI. Full article

Metastatic breast cancer (MBC) patient outcomes may vary according to distinct health care payers and different countries. We compared 291 Alberta (AB), Canada and 9429 US patients < 65 with de novo MBC diagnosed from 2010 through 2014. Data were extracted from the provincial Breast Data Mart and from the National Cancer Institute’s SEER program. US patients were divided by insurance status (US privately insured, US Medicaid or US uninsured). Kaplan-Meier and log-rank analyses were used to assess differences in OS and hazard ratios (HR) were estimated using Cox models. Multivariate models were adjusted for age, surgical status, and biomarker profile. No difference in OS was noted between AB and US patients (HR = 0.92 (0.77–1.10), p = 0.365). Median OS was not reached for the US privately insured and AB groups, and was 11 months and 8 months for the US Medicaid and US uninsured groups, respectively. The 3-year OS rates were comparable between US privately insured and AB groups (53.28% (51.95–54.59) and 55.54% (49.49–61.16), respectively). Both groups had improved survival (p < 0.001) relative to the US Medicaid and US uninsured groups [39.32% (37.25–41.37) and 40.53% (36.20–44.81)]. Our study suggests that a universal health care system is not inferior to a private insurance-based model for de novo MBC. Full article

A 79-year-old HIV-negative Caucasian man with a medical history of smoking 20 pack-years (quit 40 years prior), early-stage non-small cell lung cancer status post-lobectomy 13 years earlier at an outside hospital without evidence of recurrence, and benign prostatic hypertrophy was diagnosed with synchronous very high-risk prostate adenocarcinoma and early-stage anal basaloid squamous cell carcinoma. He proceeded to undergo concurrent treatment for these tumors, consisting of androgen deprivation therapy, external beam radiation therapy, and a brachytherapy boost for the prostate adenocarcinoma; for the anal carcinoma, he was treated with definitive chemoradiation. Over 3.5 years since the completion of radiotherapy, he remains in clinical and biochemical remission. Full article

Glioblastoma (GBM) is the most common primary malignant brain tumor in adults, and over half of patients with newly diagnosed GBM are over the age of 65. Management of glioblastoma in older patients includes maximal safe resection followed by either radiation, chemotherapy, or combined modality treatment. Despite recent advances in the treatment of older patients with GBM, survival is still only approximately 9 months compared to approximately 15 months for the general adult population, suggesting that further research is required to optimize management in the older population. The Comprehensive Geriatric Assessment (CGA) has been shown to have a prognostic and predictive role in the management of older patients with other cancers, and domains of the CGA have demonstrated an association with outcomes in GBM in retrospective studies. Furthermore, the CGA and other geriatric assessment tools are now starting to be prospectively investigated in older GBM populations. This review aims to outline current treatment strategies for older patients with GBM, explore the rationale for inclusion of geriatric assessment in GBM management, and highlight recent data investigating its implementation into practice. Full article

Nipple-areolar complex (NAC)-related complications are common during nipple-sparing mastectomy (NSM), with obesity as a risk factor. Although the incidence of NAC-related complications after robotic NSM (RNSM) with immediate breast reconstruction (IBR) is lower than that after conventional NSM, it remains one of the most unwanted complications. We aimed to evaluate body composition-based risk factors for NAC-related complications after RNSM with IBR. Data of 92 patients with breast cancer who underwent RNSM with IBR using direct-to-implant or tissue expander from November 2017 to September 2020 were analyzed retrospectively. Risk factors for NAC-related complications were identified with a focus on body composition using preoperative transverse computed tomography at the third lumbar vertebra level. Postoperative complications were assessed for 6 months. The most common complication was NAC ischemia, occurring in 15 patients (16%). Multivariate analysis revealed a low skeletal muscle index/total adipose tissue index (SMI/TATI) ratio as an independent NAC ischemia risk factor. An increase in the SMI/TATI ratio by one decreased the incidence of NAC ischemia by 0.940-fold (p = 0.030). A low SMI/TATI ratio is a risk factor for postoperative NAC ischemia in patients undergoing RNSM with IBR for breast cancer. Preoperative body composition-focused evaluation is more valuable than simple body mass index assessment. Full article

The management of COVID-19 in hematopoietic cell transplant (HCT) recipients represents a special challenge given the variable states of immune dysregulation and altered vaccine efficacy in this population. A systematic search (Ovid Medline and Embase on 1 June 2021) was needed to better understand the presenting features, prognostic factors, and treatment options. Of 897 records, 29 studies were identified in our search. Most studies reporting on adults and pediatric recipients described signs and symptoms that were typical of COVID-19. Overall, the mortality rates were high, with 21% of adults and 6% of pediatric HCT recipients succumbing to COVID-19. The factors reported to be associated with increased mortality included age (HR = 1.21, 95% CI 1.03–1.43, p = 0.02), ICU admission (HR = 4.42, 95% CI 2.25–8.65, p < 0.001 and HR = 2.26, 95% CI 1.22–4.20, p = 0.01 for allogeneic and autologous HCT recipients), and low platelet count (OR = 21.37, 95% CI 1.71–267.11, p = 0.01). Performance status was associated with decreased mortality (HR = 0.83, 95% CI 0.74–0.93, p = 0.001). A broad range of treatments was described, although no controlled studies were identified. The risk of bias, using the Newcastle–Ottawa scale, was low. Patients undergoing HCT are at a high risk of severe morbidity and mortality associated with COVID-19. Controlled studies investigating potential treatments are required to determine the efficacy and safety in this population. Full article