The efficacy of immunotherapy targeting the PD-1/PD-L1 pathway has previously been demonstrated in metastatic head and neck squamous cell carcinoma (HNSCC). Stereotactic Body Radiotherapy (SBRT) aims ...at ablating metastatic lesions and may play a synergistic role with immunotherapy. The purpose of this study is to assess the safety and efficacy of triple treatment combination (TTC) consisting of the administration of durvalumab and tremelimumab in combination with SBRT in metastatic HNSCC.
This is a phase I/II single arm study that will include 35 patients with 2-10 extracranial metastatic lesions. Patients will receive durvalumab (1500 mg IV every 4 weeks (Q4W)) and tremelimumab (75 mg IV Q4W for a total of 4 doses) until progression, unacceptable toxicity or patient withdrawal. SBRT to 2-5 metastases will be administered between cycles 2 and 3 of immunotherapy. The safety of the treatment combination will be evaluated through assessment of TTC-related toxicities, defined as grade 3-5 toxicities based on Common Terminology Criteria for Adverse Events (v 4.03), occurring within 6 weeks from SBRT start, and that are definitely, probably or possibly related to the combination of all treatments. We hypothesize that dual targeting of PD-L1 and CTLA-4 pathways combined with SBRT will lead to < 35% grade 3-5 acute toxicities related to TTC. Progression free survival (PFS) will be the primary endpoint of the phase II portion of this study and will be assessed with radiological exams every 8 weeks using the RECIST version 1.1 criteria.
The combination of synergistic dual checkpoints inhibition along with ablative radiation may significantly potentiate the local and systemic disease control. This study constitutes the first clinical trial combining effects of SBRT with dual checkpoint blockade with durvalumab and tremelimumab in the treatment of metastatic HNSCC. If positive, this study would lead to a phase III trial testing this treatment combination against standard of care in metastatic HNSCC.
NCT03283605 . Registration date: September 14, 2017; version 1.
Cancer is a leading cause of disease burden worldwide and the first cause of mortality in Canada with 30.2% of deaths attributable to cancer. Given aging of the population and the improvement of ...prevention and treatment protocols, the number of cancer survivors is steadily increasing. These individuals have unique physical and mental health needs some of which can be addressed by integrating physical activity promotion into ongoing and long-term care. Despite the benefits of being active, delivery of PA programs for cancer patients in both clinical and community settings remains challenging. This knowledge-to-action protocol-called Kiné-Onco-aims to develop a practice guideline for the delivery, implementation, and scaling-up of cancer-specific physical activity promotion programs and services in clinical and community settings located in Québec, Canada. The Kiné-Onco project involves knowledge synthesis of scientific and grey literature to establish the benefits and added value of physical activity for cancer patients and survivors, describes current practices in delivering physical activity programs, analyses quantitative data from electronic health records (EHR) of patients participating in a novel hospital-based physical activity program, collects and analyses qualitative data from patients and healthcare providers interviews about lived experience, facilitators, and barriers to physical activity promotion, outlines deliberative workshops among multidisciplinary team members to develop implementation guidelines for physical activity promotion, and summarizes a variety of knowledge transfer and exchange activities to disseminate the practice guidelines. This paper describes the protocol for a knowledge-to-action project aimed at producing and sharing actionable evidence. Our aim is that physical activity promotion programs and services be scaled up in such a way as to successfully integrate physical activity promotion throughout cancer treatment and survivorship in order to improve the physical and mental health of the growing population of individuals having received a cancer diagnosis.
The antiepidermal growth factor receptor monoclonal antibody cetuximab has improved survival in patients with metastatic, chemotherapy-refractory, wild-type K-RAS colorectal cancer. The addition of ...brivanib, a tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor and fibroblast growth factor receptor, to cetuximab has shown encouraging early clinical activity.
Patients with metastatic colorectal cancer previously treated with combination chemotherapy were randomly assigned 1:1 to receive cetuximab 400 mg/m(2) intravenous loading dose followed by weekly maintenance of 250 mg/m(2) plus either brivanib 800 mg orally daily (arm A) or placebo (arm B). The primary end point was overall survival (OS).
A total of 750 patients were randomly assigned (376 in arm A and 374 in arm B). Median OS in the intent-to-treat population was 8.8 months in arm A and 8.1 months in arm B (hazard ratio HR, 0.88; 95% CI, 0.74 to 1.03; P = .12). Median progression-free survival (PFS) was 5.0 months in arm A and 3.4 months in arm B (HR, 0.72; 95% CI, 0.62 to 0.84; P < .001). Partial responses observed (13.6% v 7.2%; P = .004) were higher in arm A. Incidence of any grade ≥ 3 adverse events was 78% in arm A and 53% in arm B. Fewer patients received ≥ 90% dose-intensity of both cetuximab (57% v 83%) and brivanib/placebo (48% v 87%) in arm A versus arm B, respectively.
Despite positive effects on PFS and objective response, cetuximab plus brivanib increased toxicity and did not significantly improve OS in patients with metastatic, chemotherapy-refractory, wild-type K-RAS colorectal cancer.
Background The PAROLE-Onco program was introduced in the province of Quebec, Canada in 2019. It integrates accompanying patients (APs), i.e., people who have been affected by cancer, into the ...clinical team as full members. These APs use their experiential knowledge with people undergoing treatment and with clinical teams. The aim of this paper is to evaluate, within the framework of two university medical centers, the perceptions of breast cancer patients who receive support from APs, particularly in terms of their active involvement in their care trajectory. Methods A qualitative study based on semi-structured interviews with accompanied patients was performed. Fourteen individual interviews were conducted between July and September 2021 with women presenting different profiles in terms of age, education, professional status, type of treatment, family situation, and clinical background. The data were analyzed using thematic analysis, focusing on patients' perceptions of APs' contributions and suggested improvements for accessing AP support. Results Three themes emerged from the semi-structured interviews: communication modalities used to connect patients with their APs, the characteristics of the support provided by APs, and the perceived effects of this support on the patients. Patients expressed a preference for telephone communication, highlighting its convenience and accessibility. The support provided by APs included emotional and informational support, neutrality, and adaptability. This relationship improved patient communication, reduced anxiety, helped regain control, and enhanced overall quality of life. The results emphasized the added value of APs in complementing the support offered by healthcare professionals. Patients noted the critical role of APs in helping them navigate the healthcare system, better understand their treatment processes, and manage their emotions. The ability of APs to provide practical advice and emotional reassurance was particularly valued. Overall, the findings underscored the significant impact of AP support on patients' experiences and highlighted areas for enhancing this service. Conclusion This study highlights, during the care trajectory of people affected by breast cancer, APs' contribution to patients' emotional well-being because they improve, in particular, the management of emotions and communication with health professionals. Keywords: Accompanying patients, Accompanied patient, Peer support, Oncology, Patient care experience, Clinical team
Public health measures have imposed drastic reductions in cancer screening programs at the beginning of the COVID-19 pandemic, with an unknown impact on the diagnosis and staging of colorectal cancer ...(CRC).
Newly diagnosed CRC cases at the Centre Hospitalier de l'Université de Montréal (CHUM) were divided into two groups according to the timeline: pre-pandemic (1 January 2018-12 March 2020), and pandemic (13 March 2020-30 June 2021) periods. Colonoscopy, surgery, and staging at diagnosis during the pandemic period were compared to the pre-pandemic period.
254 CRC diagnoses were made during the pre-pandemic period in comparison to 125 during the pandemic period. Mean diagnosis rates were lower in the pandemic period (7.8 vs. 9.8 diagnoses/month,
= 0.048). Colonoscopy deadlines were less respected in the pandemic period (51.7% vs. 38.3%,
= 0.049). The rate of elective surgery did not differ (2.9 vs. 3.5 surgeries/month,
= 0.39) and mean delays were similar (58.6 vs. 60.4 days,
= 0.77). Stages at diagnosis did not differ (
= 0.17). Most of the delayed colonoscopies led to a stage 0 or I CRC (
= 0.2).
In our center, the COVID-19 pandemic resulted in a decreased rate of CRC diagnosis and increased endoscopic delays without affecting the rate of advanced stage disease. Delays to surgery were quite similar once the CRC diagnosis was established.
: 5-FU-based chemoradiotherapy (CRT) could be associated with severe treatment-related toxicities in patients harboring at-risk
polymorphisms.
: 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
genotyping. We aimed to determine the effect of
genotyping on grade ≥3 toxicities.
: 181 patients were analyzed (87 patients before and 94 patients following
screening). Of the patients, 91% (
= 86) were prospectively genotyped for the
allele. Of those screened, 2% (
= 2/87) demonstrated a heterozygous
mutation. Extended genotyping of
-negative patients later allowed for the retrospective identification of six additional patients with alternative
variants (two c.2846A>T and four c.1236G>A mutations). Grade ≥3 toxicities occurred in 71% of the patients before
screening versus 62% following upfront genotyping (
= 0.18). When retrospectively analyzing additional non-
variants, the relative risks for mucositis (RR 2.36 1.39-2.13,
= 0.0063), dysphagia (RR 2.89 1.20-5.11,
= 0.019), and aspiration pneumonia (RR 13 2.42-61.5),
= 0.00065) were all significantly increased.
: The
, c.2846A>T, and c.1236G>A polymorphisms are associated with an increased risk of grade ≥3 toxicity to 5-FU. Upfront
genotyping can identify patients in whom 5-FU-related toxicity should be avoided.
Despite the availability of healthcare and community services dedicated to cancer survivors, these remain underutilized by young adults living with cancer (YAC; aged 18-39). A workshop was organized ...in Montréal, Canada, to identify the needs of YAC during their post-treatment transition period and explore existing services dedicated to YAC.Background and objectivesDespite the availability of healthcare and community services dedicated to cancer survivors, these remain underutilized by young adults living with cancer (YAC; aged 18-39). A workshop was organized in Montréal, Canada, to identify the needs of YAC during their post-treatment transition period and explore existing services dedicated to YAC.We recruited seventeen stakeholders (N = 17), including seven YAC, to participate in a one-day workshop to consult about best approaches and practices to meet the needs of YAC, post-treatment. All discussions were transcribed, and a thematic qualitative analysis was performed.MethodsWe recruited seventeen stakeholders (N = 17), including seven YAC, to participate in a one-day workshop to consult about best approaches and practices to meet the needs of YAC, post-treatment. All discussions were transcribed, and a thematic qualitative analysis was performed.Two main findings were identified: differences and similarities among stakeholders about perceptions of post-treatment needs; and suggestions to meet YAC needs following treatment.ResultsTwo main findings were identified: differences and similarities among stakeholders about perceptions of post-treatment needs; and suggestions to meet YAC needs following treatment.Results demonstrate the importance of collaboration among multiple stakeholders, including YAC, when designing services for YAC. Results include suggestions to improve services available through community or healthcare centres.ConclusionsResults demonstrate the importance of collaboration among multiple stakeholders, including YAC, when designing services for YAC. Results include suggestions to improve services available through community or healthcare centres.
Contexte et objectifs : Bien qu’il existe des soins de santé et des services communautaires aux survivants, ceux-ci sont sous-utilisés par les jeunes adultes atteints du cancer (c’est-à-dire âgés de ...18 à 39 ans). Un atelier a été organisé à Montréal (Canada) visant à cerner les besoins des JAC signalés par cette population au cours de la transition post-thérapeutique et à examiner les services qui leur sont offerts actuellement.
Méthodologie : Dix-sept intervenants (n = 17) ont été recrutés, dont 7 jeunes adultes ayant eu le cancer (JAC), et nous leur avons demandé de prendre part à un atelier d’une journée visant à examiner les meilleures approches et pratiques qui permettraient de combler les besoins des JAC après le traitement. Toutes les discussions ont été transcrites, puis une analyse qualitative des thèmes a été effectuée.
Résultats : Deux grands constats ressortent : les différences et les similitudes entre les parties prenantes concernant les perceptions des besoins post-traitement ; et des suggestions pour répondre aux besoins des JAC, après le traitement.
Conclusions : Les résultats montrent l’importance de la collaboration entre les différents intervenants, y compris les JAC, lorsqu’il s’agit de concevoir des services destinés aux JAC. Les résultats comprennent des suggestions visant à améliorer la qualité des services offerts dans la collectivité et les établissements de soins de santé.
Mots clés : participation du patient, participation de la collectivité, survie, jeune adulte, cancer, services de soins de santé
National Cancer Institute of Canada Clinical Trials Group CO.17 demonstrated the antiepidermal growth factor receptor (anti-EGFR) monoclonal antibody cetuximab improves overall and progression-free ...survival in patients with advanced, chemotherapy-refractory colorectal cancer (CRC), particularly in patients with wild-type KRAS tumors. This article reports the health-related quality-of-life (HRQL) outcomes from CO.17.
Patients (N = 572) with pretreated EGFR-detectable advanced CRC were randomly assigned to cetuximab and best supportive care (BSC) or to BSC alone. HRQL primary end points assessed by the EORTC QLQ-C30 were physical function (PF) and global health status (GHS); mean changes from baseline to 8 and 16 weeks were assessed. Post hoc analysis by KRAS mutation status was performed.
Questionnaire compliance was 94% at baseline, but it declined differentially (67% v 47% for cetuximab v BSC at 16 weeks). PF change scores were -3.9 for cetuximab and -8.6 for BSC (P = .046) at 8 weeks and were -5.9 and -12.5 for cetuximab and BSC, respectively, (P = .027) at 16 weeks. GHS change scores were -0.5 and -7.1 (P = .008) at 8 weeks and were -3.6 and -15.2 (P = .008) at 16 weeks for cetuximab and BSC, respectively. In patients who had tumors with wild-type KRAS status, cetuximab resulted in less PF deterioration at 8 weeks (-0.7 v -7.2; P = .11) and 16 weeks (-3.4 v -13.8; P = .008) compared with BSC. Patients with wild-type status who received cetuximab experienced improved GHS at 8 weeks, whereas patients who received BSC alone deteriorated (3.2 v -7.7; P = .002). Cetuximab preserved GHS at 16 weeks (-0.2 v -18.1; P < .001). No significant differences were noted between study arms for patients with mutated KRAS tumors.
Cetuximab offers important HRQL and survival benefits for pretreated patients with advanced, wild-type KRAS CRC.
To determine the rates of organ preservation and function in patients with advanced laryngeal and hypopharyngeal carcinomas treated with concurrent chemoradiotherapy (CRT).
Between April 1999 and ...September 2005, 82 patients with advanced laryngeal (67%) and hypopharyngeal carcinomas (33%) underwent conventional radiotherapy and concurrent platinum-based chemotherapy with curative intent. Sixty-two patients were male (75.6%). The median age was 59 years. Eighteen patients (22%) were in Stage III and 64 (78%) were in Stage IV. The median radiation dose was 70 Gy. The median potential follow-up was 3.9 years.
Overall survival and disease-free survival were respectively 63% and 73% at 3 years. Complete response rate from CRT was 75%. Nineteen patients (23%) experienced significant long-term toxicity after CRT: 6 (7.3%) required a percutaneous endoscopic gastrostomy, 5 (6%) had persistent Grade 2 or 3 dysphagia, 2 (2.4%) had pharyngoesophageal stenosis requiring multiple dilations, 2 (2.4%) had chronic lung aspiration, and 7 (8.5%) required a permanent tracheostomy. Four patients (4.9%) underwent laryngectomy without pathologic evidence of disease. At last follow-up, 5 (6%) patients were still dependent on a gastrostomy. Overall, 42 patients (52%) were alive, in complete response, with a functional larynx and no other major complications.
In our institution, CRT for advanced hypopharyngeal and laryngeal carcinoma has provided good overall survival and locoregional control in the majority of patients, but a significant proportion did not benefit from this approach because of either locoregional failure or late complications. Better organ preservation approaches are necessary to improve locoregional control and to reduce long-term toxicities.
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