Current Oncology

The Canadian Real-world Evidence for Value in Cancer Drugs (CanREValue) Collaboration was established to develop a framework for generating and using real-world evidence (RWE) to inform the reassessment of cancer drugs following initial health technology assessment (HTA). The Reassessment and Uptake Working Group (RWG) is one of the five established CanREValue Working Groups. The RWG aims to develop considerations for incorporating RWE for HTA reassessment and strategies for using RWE to reassess drug funding decisions. Between February 2018 and December 2019, the RWG attended four teleconferences (with follow-up surveys) and two in-person meetings to discuss recommendations for the development of a reassessment process and potential barriers and facilitators. Modified Delphi methods were used to gather input. A draft report of recommendations (to December 2018) was shared for public consultation (December 2019 to January 2020). Initial considerations for developing a reassessment process were proposed. Specifically, reassessment can be initiated by diverse stakeholders, including decision makers from public drug plans or industry stakeholders. The reassessment process should be modelled after existing deliberation and recommendation frameworks used by HTA agencies. Proposed reassessment outcome categories include maintaining status quo, revisiting funding criteria, renegotiating price, or disinvesting. Overall, these initial considerations will serve as the basis for future advancements by the Collaboration. Full article

Introduction: the diagnostic performance of [⁶⁴Cu]-DOTAGA-PSMA PET–CT imaging was compared retrospectively to [¹⁸F]-PSMA PET–CT in prostate cancer patients with recurrent disease and in the primary staging of selected patients with advanced local and possible metastatic disease. Methods: We retrospectively selected a total of 100 patients, who were consecutively examined in our department, with biochemical recurrence after radical prostatectomy or who had progressive local and possible metastatic disease in the last 3 months prior to this investigation. All patients were examined with a dedicated PET–CT scanner (Biograph; Siemens Healthineers). A total of 250 MBq (3.5 MBq per kg bodyweight, range 230–290 MBq) of [⁶⁴Cu]-DOTAGA-PSMA or [¹⁸-F]-PSMA was applied intravenously. PET images were performed 1 h post-injection (skull base to mid-thigh). The maximum standardized uptake values (SUVmax) of PSMA-positive lesions and the mean standardized uptake value (SUVmean) of the right liver lobe were measured. Results: All but 9/50 of the patients (18%; PSA range: 0.01–0.7 µg/L) studied with [⁶⁴Cu]-DOTAGA-PSMA and 6/50 of the ones (12%; PSA range: 0.01–4.2) studied with [¹⁸F]-PSMA had at least one positive PSMA lesion shown by PET–CT. The total number of lesions was higher with [⁶⁴Cu]-DOTAGA-PSMA (209 vs. 191); however, the median number of lesions was one for [⁶⁴Cu]-DOTAGA-PSMA and two for [¹⁸F]-PSMA. Interestingly, the median SUVmean of the right liver lobe was slightly higher for [¹⁸F]-PSMA (11.8 vs. 8.9). Conclusions: [⁶⁴Cu]-DOTAGA-PSMA and [¹⁸F]-PSMA have comparable detection rates for the assessment of residual disease in patients with recurrent or primary progressive prostate cancer. The uptake in the liver is moderately different, and therefore at least the SUVs of the lesions in both studies would not be comparable. Full article

Background: Combination therapy with anti-programmed death-ligand 1 monoclonal antibody atezolizumab plus anti-vascular endothelial growth factor agent bevacizumab (Atezo/Bev) was approved in 2020 as a first-line treatment for unresectable hepatocellular carcinoma (HCC). Atezo/Bev therapy is relatively well tolerated; however, factors that can predict its response have not yet been reported. Thus, we aimed to investigate whether the pretreatment neutrophil-to-lymphocyte ratio (NLR) could predict the therapeutic response in patients with HCC treated with Atezo/Bev therapy. Methods: We analyzed the course of 40 patients with HCC who received Atezo/Bev therapy at our hospital and attempted to identify pretreatment factors that could predict response by comparing those who achieved disease control with those who did not. Results: The pretreatment NLR value in patients who achieved disease control was significantly lower than that in patients with disease progression (2.47 vs. 4.48, p = 0.013). Using the optimal NLR cut-off value for predicting response (3.21) determined by receiver operating characteristic curve analysis, patients with NLR ≤ 3.21 had significantly better progression-free survival than those with NLR > 3.21 (p < 0.0001), although there were no significant differences in liver function or tumor-related background factors between the two groups. Conclusions: The pretreatment NLR value may be a useful predictor of response to Atezo/Bev therapy for HCC. Full article

While developments in cancer therapeutics have greatly reduced morbidity and mortality in females with breast cancer, it comes at a cost of an increased risk of cardiovascular complications. In particular, anthracyclines, like doxorubicin, which are a mainstay of current chemotherapy regimens, are associated with dose-dependent cardiotoxicity. Exercise has been widely accepted as an effective intervention in reducing cardiovascular risk in a variety of different clinical conditions. However, the benefits of exercise in anthracycline-mediated cardiotoxicity are not clearly understood. First, this review discusses the pre-clinical studies which have elucidated the cardioprotective mechanisms of aerobic and resistance exercise in improving cardiovascular function in the setting of anthracycline treatment. Next, it aims to summarize the results of aerobic and resistance exercise clinical trials conducted in females with breast cancer who received anthracycline-based chemotherapy. The review further discusses the current exercise guidelines for women undergoing chemotherapy and contraindications for exercise. Finally, the review addresses gaps in research, specifically the need for further clinical trials to establish a recommended exercise prescription within this patient population. Full article

Lung cancer is the most fatal and frequently diagnosed malignant tumor. Neoadjuvant therapy is a promising approach for prolonging survival and increasing the chance of cure rates for patients with potentially resectable disease. Currently, many therapeutic alternatives, including chemotherapy, targeted therapy, and immunotherapy, are continually being explored to enrich the content of neoadjuvant therapy. However, neoadjuvant therapy remains to have no unified evaluation standards. Overall survival (OS) is the “gold standard” for evaluating the clinical benefit of cancer treatment, but it needs years for a reliable evaluation. Hence, researchers need to identify surrogate endpoints that can predict OS accurately and reliably without long follow-up periods. In this review, we describe the research progress of different neoadjuvant therapies and explore their response evaluation, aiming to identify stronger predictors of OS. Full article

The most common adverse reactions to rituximab are infusion-related reactions (IRR). We evaluated the efficacy of split dosing the first rituximab infusion over two days to reduce IRR incidence in patients with hematological cancer and a high lymphocyte count. This is a retrospective observational study conducted in two healthcare centers in Quebec, Canada. The study enrolled patients with white blood cell counts ≥25.0 × 10⁹/L who received their first rituximab dose for hematological cancer between December 2007 and May 2020. One healthcare center used asymmetrical split dosing, while the other used symmetrical split dosing. A total of 183 treatment episodes were collected from 143 patients. Among patients who received a fractionated dosing schedule, 42% developed an IRR from the first rituximab infusion compared with 50% for the standard protocol (adjusted relative risk, 0.89; p = 0.540). No significant difference was observed in IRR severity between either groups. However, 24% of patients who received the asymmetrical protocol developed an IRR compared to 68% for the symmetrical protocol (adjusted relative risk, 0.32; p = 0.003). These results suggest that an asymmetrical split dosing could be effective in reducing the incidence of IRR and is preferable to a symmetrical one. Full article

Benign ureteroenteric anastomosis strictures (UESs) are one of many critical complications that may cause irreversible disability following robot-assisted radical cystectomy (RARC). Previous studies have shown that the incidence rates of UES after RARC can reach 25.3%, with RARC having higher UES incidence rates compared to open radical cystectomy. Various known and unknown factors are involved in the occurrence of UES. To minimize the incidence of UES after RARC, our group has standardized the procedure and technique for intracorporeal urinary diversion by applying the following five strategies: (1) wide delicate dissection of the ureter and preservation of the periureteral tissues; (2) gentle handling of the ureter and security of periureteral tissues at the anastomotic site; (3) use of indocyanine green to confirm good blood supply; (4) standardization of the ample ureteral spatulation length for Wallace ureteroenteric anastomosis through objective measurements; and (5) development of an institutional standardized procedure manual. This review focused on the incidence, etiology, prevention, and management of UES after RARC to bring attention to the incidence of this complication while also proposing standardized surgical procedures to minimize its incidence after RARC. Full article

Small cell lung cancer (SCLC) remains a poorly understood disease with aggressive features, high relapse rates, and significant morbidity as well as mortality, yet persistently limited treatment options. For three decades, the treatment algorithm of SCLC has been stagnant despite multiple attempts to find alternative therapeutic options that could improve responses and increase survival rates. On the other hand, immunotherapy has been a thriving concept that revolutionized treatment options in multiple malignancies, rendering previously untreatable diseases potentially curable. In extensive stage SCLC, immunotherapy significantly altered the course of disease and is now part of the treatment algorithm in the first-line setting. Nevertheless, the important questions that arise are how best to implement immunotherapy, who would benefit the most, and finally, how to enhance responses. Full article

Background: Accumulating evidence indicates tumor-promoting roles of synaptotagmin 13 (SYT13) in several cancers; however, no studies have investigated its expression in breast cancer (BC). This study aimed to clarify the significance of SYT13 in BC. Methods: SYT13 mRNA expression levels were evaluated in BC cell lines. Polymerase chain reaction (PCR) array analysis was conducted to determine the correlation between expression levels of SYT13 and other tumor-associated genes. Then, the association of SYT13 expression levels in the clinical BC specimens with patients’ clinicopathological factors was evaluated. These findings were subsequently validated using The Cancer Genome Atlas (TCGA) database. Results: Among 13 BC cell lines, estrogen receptor (ER)-positive cells showed higher SYT13 mRNA levels than ER-negative cells. PCR array analysis revealed positive correlations between SYT13 and several oncogenes predominantly expressed in ER-positive BC, such as estrogen receptor 1, AKT serine/threonine kinase 1, and cyclin-dependent kinases 4. In 165 patients, ER-positive specimens exhibited higher SYT13 mRNA expression levels than ER-negative specimens. The TCGA database analysis confirmed that patients with ER-positive BC expressed higher SYT13 levels than ER-negative patients. Conclusion: This study suggests that SYT13 is highly expressed in ER-positive BC cells and clinical specimens, and there is a positive association of SYT13 with the ER signaling pathways. Full article

The therapeutic and diagnostic modalities of light are well known, and derivative photodynamic reactions with photosensitizers (PSs), specific wavelengths of light exposure and the existence of tissue oxygen have been developed since the 20th century. Photodynamic therapy (PDT) is an effective local treatment for cancer-specific laser ablation in malignancies of some organs, including the bile duct. Although curability for extrahepatic cholangiocarcinoma is expected with surgery alone, patients with unresectable or remnant biliary cancer need other effective palliative therapies, including PDT. The effectiveness of PDT for cholangiocarcinoma has been reported experimentally or clinically, but it is not the standard option now due to problems with accompanied photosensitivity, limited access routes of irradiation, tumor hypoxia, etc. Novel derivative treatments such as photoimmunotherapy have not been applied in the field hepatobiliary system. Photodynamic diagnosis (PDD) has been more widely applied in the clinical diagnoses of liver malignancies or liver vascularization. At present, 5-aminolevulinic acid (ALA) and indocyanine green (ICG) dyes are mainly used as PSs in PDD, and ICG has been applied for detecting liver malignancies or vascularization. However, no ideal tools for combining both PDD and PDT for solid tumors, including hepatobiliary malignancies, have been clinically developed. To proceed with experimental and clinical trials, it is necessary to clarify the effective photosensitive drugs that are feasible for photochemical diagnosis and local treatment. Full article

Since ancient times, breast cancer treatment has crucially relied on surgeons and clinicians making great efforts to find increasingly conservative approaches to cure the tumor. In the Halstedian era (mid-late 19th century), the predominant practice consisted of the radical and disfiguring removal of the breast, much to the detriment of women’s psycho-physical well-being. Thanks to enlightened scientists such as Professor Umberto Veronesi, breast cancer surgery has since impressively progressed and adopted a much more conservative approach. Over the last three decades, a better understanding of tumor biology and of its significant biomarkers has made the assessment of genetic and molecular profiles increasingly important. At the same time, neo-adjuvant treatments have been introduced, and great improvements in genetics, imaging technologies and in both oncological and reconstructive surgical techniques have been made. The future of breast cancer management must now rest on an ever more precise and targeted type of surgery that, through an increasingly multidisciplinary and personalized approach, can ensure oncological radicality while offering the best possible quality of life. Full article

Objective: Self-rated health (SRH) is a salient patient outcome for cancer survivors, and depressive mood and education are known determinants of cancer survivors’ SRH. Moving beyond the well-established direct association between depressive mood, education, and SRH among cancer survivors, this epidemiological study investigated the pathoplastic role of education on depressive mood in relation to SRH among a nationally representative sample of cancer survivors in the United States. Methods: The 2019 National Health Interview Survey was analyzed using data from adult participants (≥18 years old) who self-reported as cancer survivors (n = 3844). Ordered logistic regression was used to evaluate the direct impact of depressive mood and education in relation to SRH. In addition, the pathoplastic moderating effect was evaluated using ordered logistic regression with an interaction term of depressive mood and education in the regression model. All analyses adjusted for complex sample weights so that findings are nationally representative. Results: After adjusting for all covariates, U.S. cancer survivors’ depressive mood was significantly associated with lower SRH, and U.S. cancer survivors’ higher education was significantly associated with higher SRH. As a pathoplastic moderator, cancer survivors’ education significantly moderated the association between depressive mood and SRH. The negative association between depressive mood and SRH was significantly greater among those with higher education. Conclusion: Moving beyond the direct association between depressive mood, education, and SRH, education served as a pathoplastic moderator in relation to depressive mood and SRH. Psycho-oncology providers need to be mindful of the “protective-risk” effect of education in relation to cancer survivors’ depressive mood and SRH. Full article

There is evidence that achieving a dose intensity > 80% in adjuvant colon cancer treatment improves survival. In total, 192 consecutive patients with resected stage III and high-risk stage II colon cancer that received adjuvant chemotherapy were retrospectively analyzed. Patients who received at least 6 weeks of adjuvant therapy were included. The primary objective was to assess the influence of dose index (DI) and relative dose intensity (RDI) on DFS and OS at 3 and 5 years in patients receiving fluorouracil-based doublet therapy with oxaliplatin (FOLFOX)(5-FU and oxaliplatin assessed separately), or capecitabine monotherapy. In the capecitabine group, DFS rates for 3 and 5 years were 66.7% and 57.6%, respectively, while OS rates were 80.3% and 66.7%, respectively. Those who received FOLFOX had DFS rates of 76.9% and 71.2% at 3 and 5 years, respectively. OS rates were 86.4% and 76.7% at 3 and 5 years, respectively. Median RDI was 73.8% for capecitabine and 76.3% and 85.6% for the oxaliplatin and 5-FU components respectively. Based on a multivariate analysis in patients receiving FOLFOX, those with an oxaliplatin DI > 80% had improvements in DFS and OS compared to those with an oxaliplatin DI of ≤ 80%. Otherwise, there was no significant difference in DFS or OS when comparing patients who achieved an RDI or a DI of above versus below 80% in the patients receiving adjuvant chemotherapy for resected colon cancer. Full article

Background: The multifocality and multicentrality of breast cancer (MFMCC) are the significant aspects that determine a specialist’s choice between applying breast-conserving therapy (BCT) or performing a mastectomy. This study aimed to assess the usefulness of mammography (MG), contrast-enhanced spectral mammography (CESM), and magnetic resonance imaging (MRI) in women diagnosed with breast cancer before qualifying for surgical intervention to visualize other (additional) cancer foci. Methods: The study included 60 breast cancer cases out of 630 patients initially who underwent surgery due to breast cancer from January 2015 to April 2019. MG, CESM, and MRI were compared with each other in terms of the presence of MFMCC and assessed for compliance with the postoperative histopathological examination (HP). Results: Histopathological examination confirmed the presence of MFMCC in 33/60 (55%) patients. The sensitivity of MG in detecting MFMCC was 50%, and its specificity was 95.83%. For CESM, the sensitivity was 85.29%, and the specificity was 96.15%. For MRI, all the above-mentioned parameters were higher as follows: sensitivity—91.18%; specificity—92.31%. Conclusions: In patients with MFMCC, both CESM and MRI are highly sensitive in the detection of additional cancer foci. Both CESM and MRI change the extent of surgical intervention in every fourth patient. Full article

Aims: The purpose of this study was to assess the effectiveness of a navigational radiofrequency ablation device with concurrent vertebral augmentation in the treatment of posterior vertebral body metastatic lesions, which are technically difficult to access. Primary outcomes of the study were evaluation of pain palliation and radiologic assessment of local tumor control. Materials and Methods: Thirty-five patients with 41 vertebral spinal metastases involving the posterior vertebral body underwent computed tomography-guided percutaneous targeted radiofrequency ablation, with a navigational radiofrequency ablation device, associated with vertebral augmentation. Twenty-one patients (60%) had 1 or 2 metastatic lesions (Group A) and fourteen (40%) patients had multiple (>2) vertebral lesions (Group B). Changes in pain severity were evaluated by visual analog scale (VAS). Metastatic lesions were evaluated in terms of radiological local control. Results: The procedure was technically successful in all the treated vertebrae. Among the symptomatic patients, the mean VAS score dropped from 5.7 (95% CI 4.9–6.5) before tRFA and to 0.9 (95% CI 0.4–1.3) after tRFA (p < 0.001). The mean decrease in VAS score between baseline and one week follow up was 4.8 (95% CI 4.2–5.4). VAS decrease over time between one week and one year following radiofrequency ablation was similar, suggesting that pain relief was immediate and durable. Neither patients with 1–2 vertebral metastases, nor those with multiple lesions, showed radiological signs of local progression or recurrence of the tumor in the index vertebrae during a median follow up of 19 months (4–46 months) and 10 months (4–37 months), respectively. Conclusion: Treatment of spinal metastases with a navigational radiofrequency ablation device and vertebral augmentation can be used to obtain local tumor control with immediate and durable pain relief, providing effective treatment in the multimodality management of difficult-to-reach spinal metastases. Full article

Cognitive assessment is a cornerstone of geriatric care. Cognitive impairment has the potential to significantly impact multiple phases of a person’s cancer care experience. Accurately identifying this vulnerability is a challenge for many cancer care clinicians, thus the use of validated cognitive assessment tools are recommended. As international cancer guidelines for older adults recommend Geriatric Assessment (GA) which includes an evaluation of cognition, clinicians need to be familiar with the overall interpretation of the commonly used cognitive assessment tools. This rapid review investigated the cognitive assessment tools that were most frequently recommended by Geriatric Oncology guidelines: Blessed Orientation-Memory-Concentration test (BOMC), Clock Drawing Test (CDT), Mini-Cog, Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Short Portable Mental Status Questionnaire (SPMSQ). A detailed appraisal of the strengths and limitations of each tool was conducted, with a focus on practical aspects of implementing cognitive assessment tools into real-world clinical settings. Finally, recommendations on choosing an assessment tool and the additional considerations beyond screening are discussed. Full article

Immune checkpoint and MAP kinase pathway inhibitors can significantly improve long-term survival for patients with melanoma. There is limited real-world data of these regimens’ effectiveness. We retrospectively analyzed 402 patients with unresectable and metastatic melanoma between August 2013 and July 2020 treated with immune checkpoint inhibitors and MAP kinase pathway targeted therapy in Alberta, Canada. Overall survival (OS) was compared using Kaplan–Meier and Cox regression analyses. Subgroup survival outcomes were analyzed by first-line treatment regime and BRAF mutation status. Three treatment eras were defined based on drug access: prior to August 2013, August 2013 to November 2016, and November 2016 to July 2020. Across each era, there were improvements in median OS: 11.7 months, 15.9 months, and 33.6 months, respectively. Patients with BRAF mutant melanoma had improved median OS when they were treated with immunotherapy in the first line as opposed to targeted therapy (median OS not reached for immunotherapy versus 17.4 months with targeted treatment). Patients with BRAF wild-type melanomas had improved survival with ipilimumab and nivolumab versus those treated with a single-agent PD-1 inhibitor (median OS not reached and 21.2 months). Our real-world analysis confirms significant survival improvements with each subsequent introduction of novel therapies for advanced melanoma. Full article

We reviewed patient and health care provider (HCP) surveys performed through the REaCT program. The REaCT team has performed 15 patient surveys (2298 respondents) and 13 HCP surveys (1033 respondents) that have addressed a broad range of topics in breast cancer management. Over time, the proportion of surveys distributed by paper/regular mail has fallen, with electronic distribution now the norm. For the patient surveys, the median duration of the surveys was 3 months (IQR 2.5–7 months) and the median response rate was 84% (IQR 80–91.7%). For the HCP surveys, the median survey duration was 3 months (IQR 1.75–4 months), and the median response rate, where available, was 28% (IQR 21.2–49%). The survey data have so far led to: 10 systematic reviews, 6 peer-reviewed grant applications and 19 clinical trials. Knowledge users should be an essential component of clinical research. The REaCT program has integrated surveys as a standard step of their trials process. The COVID-19 pandemic and reduced face-to-face interactions with patients in the clinic as well as the continued importance of social media highlight the need for alternative means of distributing and responding to surveys. Full article

We determined the feasibility of the combined exoscopic-endoscopic technique (CEE) as an alternative to the microscope in craniofacial resection (CFR). This retrospective study was conducted at a single institution and included eight consecutive patients with head and neck tumors who underwent CFR between September 2019 and July 2021. During the transcranial approach, microsurgery was performed using an exoscope in the same manner as in traditional microscopic surgery, and an endoscope was used at the blind spot of the exoscope. The exoscope provided images of sufficient quality to perform microsurgery, while the sphenoid sinus lumen was the blind spot of the exoscope during anterior (n = 3) and anterolateral CFR (n = 2), and the medial aspect of the temporal bone was the blind spot of the exoscope during temporal bone resection (n = 2). These blind spots were visualized by the endoscope to facilitate accurate transection of the skull base. The advantages of the exoscope and endoscope include compact size, ergonomics, surgical field accessibility, and equal visual experience for neurosurgeons and head and neck surgeons, which enabled simultaneous transcranial and transfacial surgical procedures. All the surgeries were successful without any relevant complications. CEE is effective in transcranial skull base surgery, especially CFR involving simultaneous surgical procedures. Full article