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Background: Prostate cancer is one of the most common cancers worldwide. The proper management of this cancer during the coronavirus disease 2019 (COVID-19) or similar outbreaks could be a serious challenge. Proper timing of surgery, radiotherapy, and other medical modalities are essential in providing the most effective treatment. Objective(s): This systematic review aimed at evaluating the proper management of prostate cancer during the COVID-19 outbreak. Method(s): This study was conducted from 2019 to 2022. An internet search was conducted using the keywords: Diagnosis, man-agement, radical prostatectomy, radiotherapy, hormone ablation therapy, chemotherapy and prostate cancer, and COVID-19. The visited databases included PubMed, Scopus, Web of Sciences, Google Scholar, and Scientific Information Database. The review was performed based on the preferred reporting items for a systematic review and meta-analyses (PRISMA) guidelines. Result(s): Postponing the biopsy for up to three months and adopting of non-invasive diagnostic methods were likely reasonable during the COVID-19 pandemic. Patients with cancer were more prone to severe injuries and were more likely to have serious compli-cations. Surgery, radiation therapy, brachytherapy, palliative radiation, hormone ablation therapy, and chemotherapy were among the pre-institutional treatments that had to be performed according to medical protocols as well as health and professional guide-lines. Conclusion(s): It was recommended that the prostate cancer screening should not be performed for asymptomatic men during the COVID-19 outbreak. It was also suggested that the treatment should be performed in the shortest possible time and in the safest way.Copyright © 2023, Author(s).
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Background Development of immunotherapy/molecular targeted therapy has significantly increased survival/QoL in advanced stages of NSCLC. Aim(s): to analyze outcome predictors, surrogate outcomes, and PROMs after neoadjuvant immunotherapy for initially unresectable NSCLC. Methods Initially unresectable NSCLC (2014-2021) patients who received immunotherapy +/- platinum-based chemo and/or radiotherapy evaluated after response (reduction of primary tumor and/or mediastinal lymphadenopathy/control of distant metastatic disease underwent surgical resection). PROMs were recorded using EORTC QLQ-29. Results 19 underwent salvage surgery after ICI. 14 had partial response (73.6%), 5 stable disease. Diagnosis was achieved by endobronchial ultrasound (EBUS) in 8 (42.1%), fine-needle aspiration biopsy (FNAB) in 7 (36.8%), metastasis biopsy in 4 (21.0%). 11 (57.9%) were treated with neoadjuvant platinum-based chemo before or with ICI, 1 (5.2%) pemetrexed before ICI, 5 (26.3%) radiotherapy for metastatic control. 3 (15.7%) had ICI adverse effects. Radiotherapy was never used preoperatively for pulmonary/mediastinal disease. 7 (36.8%) received adjuvant therapy (5 [26.3%] pembrolizumab, 1 [5.2%] pemetrexed, 1 [5.2%] pemetrexed + pembrolizumab). 4 (21.0%) had local relapse (no systemic relapse). Median OS was 19 months (range: 2-57.4). At 2 months, 94.7% were alive (6 months: 89.5%;31 months: 79.5%). 2 (10.5%) had local recurrence. 2 (10.5%) died due to recurrence, 1 (5.2%) to COVID. 4 (21.0%) relapsed (median DFS: 5.3 months [range: 2.2-13.0]). PROMs were reviewed retrospectively at 30 days/1 year with significant decrease in coughing, side effects of treatment, surgery-related problems. [Formula presented] Conclusions Radical surgical resections following definitive immunotherapy/immune-chemotherapy in selected initially unresectable NSCLC are feasible and safe (low surgical-related mortality and morbidity). Symptoms and surgery-related outcomes were lower with higher QoL due to a selected group of highly motivated patients. Legal entity responsible for the study The authors. Funding Ministero della Salute. Disclosure All authors have declared no conflicts of interest.Copyright © 2023 International Association for the Study of Lung Cancer. Published by Elsevier Inc.
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Background: Mammographic screening programmes reduce breast cancer mortality, but detect many small tumours with favourable biological features which may not progress during a woman's lifetime. Screen-detected cancers are treated with standard surgery and adjuvant therapies, with associated morbidities. There is a need to reduce overtreatment of good prognosis tumours and numerous studies have evaluated the omission of radiotherapy in this context. However, there is little evidence to support surgical de-escalation, although percutaneous minimally invasive treatment approaches have been described. Vacuum-assisted excision (VAE) is in widespread use for management of benign lesions and lesions of uncertain malignant potential. SMALL (ISRCTN 12240119) is designed to determine the feasibility of using this approach for treatment of small invasive tumours detected within the UK NHS Breast Screening Programme (BSP). Method(s): SMALL is a phase III multicentre randomised trial comparing standard surgery with VAE for screendetected good prognosis cancers. The main eligibility criteria are age >=47 years, unifocal grade 1 tumours with maximum diameter 15mm, which are strongly ER/PR+ve and HER2-ve, with negative clinical/radiological axillary staging. Patients are randomised 2:1 in favour of VAE or surgery;with no axillary surgery in the VAE arm. Completeness of excision is assessed radiologically, and if excision is incomplete, patients undergo open surgery. Adjuvant radiotherapy and endocrine therapy are mandated in the VAE arm but may be omitted following surgery. Co-primary end-points are: 1. Noninferiority comparison of the requirement for a second procedure following excision 2. Single arm analysis of local recurrence (LR) at 5 years following VAE Recruitment of 800 patients will permit demonstration of 10% non-inferiority of VAE for requirement of a second procedure. This ensures sufficient patients for single arm analysis of LR rates, where expected LR free survival is 99% at 5 years, with an undesirable survival probability after VAE of 97%. To ensure that the trial as a whole only has 5% alpha, the significance level for each co-primary outcome is set at 2.5% with 90% power. The Data Monitoring Committee will monitor LR events to ensure these do not exceed 3% per year. Secondary outcome measures include time to ipsilateral recurrence, overall survival, complications, quality of life and health economic analysis. A novel feature of SMALL is the integration of a QuinteT Recruitment Intervention (QRI), which aims to optimise recruitment to the study. Recruitment challenges are identified by analysing recruiter/patient interviews and audiorecordings of trial discussions, and by review of trial screening logs, eligibility and recruitment data and study documentation. Solutions to address these are developed collaboratively, including individual/group recruiter feedback and recruitment tips documents. Result(s): SMALL opened in December 2019, but recruitment halted in 2020 for 5 months due to COVID-19. At 7st July 2022, 142 patients had been randomised from 26 centres, with a randomisation rate of approximately 45%, and a per site recruitment rate of 0.4-0.5 patients/month, approaching the feasibility recruitment target of 144 patients. Drawing from preliminary QRI findings and insights from patient representatives, a recruitment tips document has been circulated (on providing balanced information about treatments, encouraging recruiters to engage with patient preferences, and explaining randomisation). Individual recruiter feedback has commenced, with wider feedback delivered across sites via recruitment training workshops. Conclusion(s): Despite pandemic-related challenges, SMALL has an excellent recruitment rate to date and is expected to have a global impact on treatment of breast cancer within mammographic screening programmes.
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Background: During the SARS-CoV-2 virus pandemic, University Hospital Birmingham NHS Trust Oncology Department incorporated the ultrahypofractionated regime of 26Gy/5 fractions alongside the moderate hypofractionated regime of 40Gy/15 fractions as part of local adjuvant breast radiotherapy treatment (RT) for eligible patients. We conducted a local study to assess the real-life experience of patients undergoing ultrahypofractionated schedule to compare feasibility and toxicity to the fast-forward trial during the COVID - 19 pandemic. Methods: A single institution, retrospective, qualitative study. Patients included had early-stage breast cancer and received adjuvant radiotherapy between 23 March 2020 and 31 May 2020, a total of 211 patients. Inclusion was irrespective of any other neoadjuvant/adjuvant treatments. Data were collected retrospectively for treatment dose, boost dose and toxicity. Results: Of the total 211 patients, 85 were treated with 26Gy in 5# and 19 patients received a boost as per the fast-forward protocol. Of these 85 patients, 15.9% did not report any skin toxicity post-treatment. 63.5% of patients reported RTOG Grade 1, 15.9% had RTOG Grade 2, and 1.6% reported RTOG Grade 3 skin toxicity. 3.2% of the patients could not be contacted for follow-up. Of the 19 patients who received a breast boost, 10.53% reported no skin changes. 78.9% reported Grade 1 skin toxicity. Both Grades 2a and 2b skin toxicity were reported by 5.26% each. The patient demographics and tumour characteristics in our study cohort were comparable to those within the fast-forward trial. In terms of post-RT skin toxicity, fewer patients reported any toxicity in the UHB patient cohort versus those in the trial, and the number of Grade 2/3 toxicities reported was also low. A delay in toxicity reporting from 2 weeks for 40Gy/15 to 3 weeks for 26Gy/5 was observed. Conclusion: Our study concluded that offering ultrahypofractionation was convenient for patients;reducing the number of hospital visits during the SARS-CoV-2 virus pandemic appeared safe in terms of acute post-RT-related skin toxicity. The reduced hospital visits limited exposure of patients and staff to the SARS-CoV-2 virus while also ensuring efficient use of Radiotherapy Department resources. Local follow-up protocols have been amended to ensure review at 3 weeks for the 26Gy/5 schedule to acknowledge the delay in acute toxicity development. To date, there is only 5-year toxicity and relapse data available from the fast-forward trial;therefore, hypofractionation schedules should be offered to patients as long as they fulfil the criteria and understand the limitations of the study as well as accelerated peer review processes in the face of the pandemic. © 2022 The Author(s).
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PURPOSE: In March 2020, a 1-week adjuvant breast radiotherapy schedule, 26 Gy in 5 fractions, was adopted to reduce the risk of COVID19 for staff and patients. This study quantifies acute toxicity rates and the effect on linac capacity. MATERIALS AND METHODS: This is a report of consecutive patients receiving ultrafractionated breast radiotherapy ( ± sequential boost) Mar-Aug 2020. Virtual consultations assessed acute skin toxicity during treatment and weeks 1, 2, 3 and 4 post treatment using CTCAE V5 scoring criteria. The number of linac minutes saved was estimated accounting for boost and DIBH use. RESULTS: In total, 128/135 (95%) patients, including 31/33 boost patients, completed at least 3/5 assessments. 0/128 (0%) reported moist desquamation not confined to skin folds or minor bleeding (Grade 3), 41/128 (32%) reported brisk erythema, moist desquamation confined to skin folds or breast swelling (Grade 2), 62/128 (48%) reported faint erythema or dry desquamation (Grade 1) as their worst skin toxicity, with the remaining 20% reporting no skin toxicity. The highest prevalence of grade 2 toxicity occurred week 1 following treatment (20%), reducing to 3% by week 4. There was no difference in toxicity between those who received a boost versus not (p = 1.00). Delivering this schedule to 135 patients over six months saved 21,300 linac minutes and 1485 hospital visits compared to a 3-week schedule. CONCLUSION: Rapidly implementing ultrahypofractionated breast radiotherapy is feasible and acute toxicity rates are acceptable even when followed by boost.
Subject(s)
Breast Neoplasms , COVID-19 , Humans , Female , Radiotherapy, Adjuvant/adverse effects , Breast Neoplasms/surgery , Prospective Studies , COVID-19/prevention & control , Mastectomy, SegmentalABSTRACT
Background: The effect of time to surgery after completion of neoadjuvant chemotherapy and outcomes in breast cancer patients remains poorly defined and unclear. Acceptable time to surgery has frequently been arbitrarily defined as between four to eight weeks. Various factors including resource limitation, scheduling conflicts, complications after chemotherapy, patient hesitation or interruptions from major events such as the recent Covid-19 pandemic can delay time to surgery, raising concern of an adverse impact on recurrence and survival outcomes. This study aims to ascertain if time to surgery after completion of neoadjuvant chemotherapy impacts disease free survival (DFS) and overall survival (OS). Material(s) and Method(s): This single-institution retrospective study included patients who underwent neoadjuvant therapy and subsequent surgery from 2006 to 2017. Demographic, clinicopathological factors and surgical data from 250 patients were analysed. 105 patients received surgery within 28 days (group 1). 119 patients received surgery within 29 to 56 days (group 2), and 26 patients received surgery after 57 days or more (group 3). DFS and OS among the three groups were compared. Result(s): Age, race, pre-chemotherapy stage, tumour type, grade, hormone receptor status, Her2 status, focality, lymphovascular invasion (LVI), radiological response to chemotherapy, type of surgery, pathological response to chemotherapy, and receipt of adjuvant radiotherapy were not significantly different between the three groups. Receipt of adjuvant chemotherapy was statistically significant (p = 0.0248) with 39 patients (37.1%) in group 1, 32 patients (26.9%) in group 2 and 3 patients (11.5%) in group 3 receiving further chemotherapy after surgery. Mean follow-up duration was 44.5 months. DFS and OS between the three groups were not found to be significantly different (p = 0.5920 and p = 0.6133 respectively). Conclusion(s): Time to surgery after completion of neoadjuvant chemotherapy did not appear to affect recurrence or survival outcomes. This result was demonstrated despite fewer patients in the group with the longest duration to surgery receiving adjuvant chemotherapy. This may be due to the efficacy of neoadjuvant chemotherapy in decreasing or eliminating micro-metastatic disease, an important factor in cancer recurrence and survival. Limitations of this study includes its retrospective nature and small sample size. Findings from this study may allow more flexibility and reduce the burden of scheduling patients for surgery within the usual four to eight week window in centres with resource and scheduling constraints. Further studies examining a larger population over a wide range of time durations could help clinicians better tailor time to surgery after neoadjuvant therapy. No conflict of interest. Copyright © 2022 Elsevier Ltd. All rights reserved
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Background: Endometrial cancer is one of the most common gynecological cancer in the world. However, the available adjuvant therapies, chemotherapy (CT) and radiotherapy (RT), demonstrated several limitations when used alone. Therefore, we conducted a meta-analysis to investigate the clinical effectiveness of chemoradiotherapy (CRT) based on overall survival (OS) and disease-free survival (DFS). Methods: A literature search was performed on five databases and one clinical trial registry to obtain all relevant articles. Search for studies was completed on September 9, 2021. A meta-analysis was conducted to determine the overall hazard ratio with the 95% Confidence Interval. Results: A total of 17 articles with 23,975 patients in the CRT vs RT group and 50,502 patients in the CRT vs CT group were included. The OS Hazard Ratios (HR) of CRT compared to RT was 0.66 (95% CI [0.59-0.75]; P < 0.00001). Compared to CT, the OS HR was 0.70 (95% CI [0.64-0.78]; P < 0.00001). CRT also significantly improved the DFS compared to CT only (HR 0.79, 95% CI [0.64-0.97]; P = 0.02) However, CRT did not improve the DFS compared to RT only, with HR of 0.71 (95% CI [0.46-1.09]; P = 0.12). Conclusion: Adjuvant CRT can significantly improve OS compared to CT or RT alone and improve the DFS compared to CT alone in patients with advanced endometrial cancer. Further research is needed to identify the optimal CRT regimen, and to whom CRT will be most beneficial.
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We investigated lung-heart toxicity and mortality in 123 women with stage I-II breast cancer enrolled in 2007-2011 in a prospective trial of adjuvant radiotherapy (TomoBreast). We were concerned whether the COVID-19 pandemic affected the outcomes. All patients were analyzed as a single cohort. Lung-heart status was reverse-scored as freedom from adverse-events (fAE) on a 1-5 scale. Left ventricular ejection fraction (LVEF) and pulmonary function tests were untransformed. Statistical analyses applied least-square regression to calendar-year aggregated data. The significance of outliers was determined using the Dixon and the Grubbs corrected tests. At 12.0 years median follow-up, 103 patients remained alive; 10-years overall survival was 87.8%. In 2007-2019, 15 patients died, of whom 11 were cancer-related deaths. In 2020, five patients died, none of whom from cancer. fAE and lung-heart function declined gradually over a decade through 2019, but deteriorated markedly in 2020: fAE dipped significantly from 4.6-4.6 to 4.3-4.2; LVEF dipped to 58.4% versus the expected 60.3% (PDixon = 0.021, PGrubbs = 0.054); forced vital capacity dipped to 2.4 L vs. 2.6 L (PDixon = 0.043, PGrubbs = 0.181); carbon-monoxide diffusing capacity dipped to 12.6 mL/min/mmHg vs. 15.2 (PDixon = 0.008, PGrubbs = 0.006). In conclusion, excess non-cancer mortality was observed in 2020. Deaths in that year totaled one-third of the deaths in the previous decade, and revealed observable lung-heart deterioration.
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Background: COVID-19 pandemic led to a drastical rearrangement within healthcare staff and facilities. Due to its high incidence, management of breast cancer (BC) was particularly critical during the COVID-19 pandemic, and the reduction of healthcare staff and facilities influenced the timing in BC care. The aim of the present report was to analyze the timing from diagnosis to surgery, from diagnosis to radiotherapy (RT) start and from surgery to RT start during the COVID-19 pandemic. Method(s): We retrospectively collected data of women with BC treated with Radiotherapy (RT) after surgery at our Institution (Department of Oncology, Radiation Oncology, S. Anna Hospital, Turin, Italy), during the COVID-19 pandemic. To evaluate patients' data according to the different stages of the pandemic, we identified 4 periods: first wave (FW), first reopening (FR), second wave (SW) and second reopening (SR). Among the 4 periods, we divided patients in 2 groups: patients who underwent adjuvant chemotherapy (CT) before RT (CT-group), and those who received exclusive adjuvant RT (non-CT group). Result(s): from early March 2020 to 31 March 2022, 464 patients were treated. After patients' selection, data from 390 patients were analyzed. Overall, the average interval between biopsy and RT in the non-CT group was 202 days during the FW (101-386), 172 days (85-242) during the FR, 136 days (69-366) during the SW, 159 days (77-455) during the SR. In the CT group, the average interval from biopsy to RT start was 337 days (224-495) during the FW, 277 days (209-496) during FR, 297 days (220-419) during the SW, and 261 days (169-447) during the SR. Conclusion(s): we reported our experience during these two years of the pandemic and how COVID-19 impacted the timing of the management of patients with BC. Overall, during the viral waves there was a remarkable increase in the interval between biopsy/surgery and RT. Nonetheless, we managed to keep optimal BC care and favorable interval trends were observed with reopening phases. Copyright: © 2022 The Author(s).
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Purpose: Cancer management is time sensitive with documented increased mortality with delays from diagnosis to treatment (1-4). National and international 'optimal care paths' and Cancer plans have been established to ensure patient centric, standardised approaches to cancer care based on best available evidence (5-7). Australian, Victorian Cancer Council-Optimal Care Pathways is a nationally endorsed guideline (5). However, there are limited publications assessing actual performance of cancer services against set guidelines (8). There are known barriers to achieving optimal cancer care with these likely amplified by the COVID19 pandemic (9-10), with these delays impacting on disease control, quality of life and significant economic costs (11-14). We aimed to assess performance against optimal care path guidelines and the potential impact of the COVID19 pandemic on achieving this ideal. Methods and Materials: Patients undergoing curative treatment with radiotherapy in Head and Neck (HN), Breast, Lung and Gastrointestinal malignancies between 2019-2021 in a single institution were included. Performance against the Victorian Cancer Council Guidelines for commencement of Radiotherapy in the definitive and neo/ adjuvant settings were analysed using the one sample t-test. The impact of COVID19 was analysed using a Mann Whitney U Test. Result(s): 733 patients between 2019-2021 were included in the retrospective analysis. Guidelines were only met by 65% breast (p = 0.2606), 35% HN-adjuvant (p =0.0000), 37% HN-definitive (p=0.6059), 74% Lung (p=0.3725), 4% oesophagus (p = 0.0002) and 33% rectal (p=0.0022) cancer patients. Percentage of patients exceeding guidelines by more than half the recommended time was 4% breast, 27% HN-adjuvant, 19% HN-definitive, 10% Lung, 76% oesophagus and 50% rectal cancer patients. There was no detrimental impact of COVID19 on guideline compliance between all tumour sites (p<0.05). Conclusion(s): This limited retrospective study highlights the persistent challenges in achieving optimal cancer care pathways designed to ensure quality care and best possible outcomes for patients. Further investigation will be done to identify the compliance across the comprehensive multi-disciplinary care path, barriers to achieving the optimal and potential solutions at a local level. However, a national strategy is required in strengthening the evidence base for the care paths, identifying the actual compliance of Cancer Services with defined 'optimal' guidelines, the barriers to achieving these and the potential qualitative/quantitative impact of not achieving 'optimal guidelines' on patients, society and the health care systems.
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Background:During the SARS-CoV-2 virus pandemic, University Hospital Birmingham NHS Trust Oncology Department incorporated the ultrahypofractionated regime of 26Gy/5 fractions alongside the moderate hypofractionated regime of 40Gy/15 fractions as part of local adjuvant breast radiotherapy treatment (RT) for eligible patients. We conducted a local study to assess the real-life experience of patients undergoing ultrahypofractionated schedule to compare feasibility and toxicity to the fast-forward trial during the COVID − 19 pandemic.Methods:A single institution, retrospective, qualitative study. Patients included had early-stage breast cancer and received adjuvant radiotherapy between 23 March 2020 and 31 May 2020, a total of 211 patients. Inclusion was irrespective of any other neoadjuvant/adjuvant treatments. Data were collected retrospectively for treatment dose, boost dose and toxicity.Results:Of the total 211 patients, 85 were treated with 26Gy in 5# and 19 patients received a boost as per the fast-forward protocol. Of these 85 patients, 15·9% did not report any skin toxicity post-treatment. 63·5% of patients reported RTOG Grade 1, 15·9% had RTOG Grade 2, and 1·6% reported RTOG Grade 3 skin toxicity. 3·2% of the patients could not be contacted for follow-up. Of the 19 patients who received a breast boost, 10·53% reported no skin changes. 78·9% reported Grade 1 skin toxicity. Both Grades 2a and 2b skin toxicity were reported by 5·26% each. The patient demographics and tumour characteristics in our study cohort were comparable to those within the fast-forward trial. In terms of post-RT skin toxicity, fewer patients reported any toxicity in the UHB patient cohort versus those in the trial, and the number of Grade 2/3 toxicities reported was also low. A delay in toxicity reporting from 2 weeks for 40Gy/15 to 3 weeks for 26Gy/5 was observed.Conclusion:Our study concluded that offering ultrahypofractionation was convenient for patients;reducing the number of hospital visits during the SARS-CoV-2 virus pandemic appeared safe in terms of acute post-RT-related skin toxicity. The reduced hospital visits limited exposure of patients and staff to the SARS-CoV-2 virus while also ensuring efficient use of Radiotherapy Department resources. Local follow-up protocols have been amended to ensure review at 3 weeks for the 26Gy/5 schedule to acknowledge the delay in acute toxicity development. To date, there is only 5-year toxicity and relapse data available from the fast-forward trial;therefore, hypofractionation schedules should be offered to patients as long as they fulfil the criteria and understand the limitations of the study as well as accelerated peer review processes in the face of the pandemic.
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Background: Coronavirus disease 2019 (COVID-19) outbreak has correlated with the disruption of screening activities and diagnostic assessments. Endometrial cancer (EC) is one of the most common gynecological malignancies and it is often detected at an early stage, because it frequently produces symptoms. Here, we aim to investigate the impact of COVID-19 outbreak on patterns of presentation and treatment of EC patients. Material(s) and Method(s): This is a retrospective study involving 54 centers in Italy. We evaluated patterns of presentation and treatment of EC patients before (period 1: March 1, 2019 to February 29, 2020) and during (period 2: April 1, 2020 to March 31, 2021) the COVID-19 outbreak. Result(s): Charts of 5,164 EC patients were retrieved. Overall, 2,718 and 2,446 women with EC received treatment in period 1 and 2, respectively. The prevalence of patients aged > 65 years was similar between the 2 study periods (1,400 [51.5%] in period 1 vs. 1,248 [51.0%];p=0.726). Considering data on the histological characterization, the prevalence of endometrioid FIGO grade 1, 2, and 3 was consistent over the study period (p=0.855). However, the prevalence of non-endometrioid EC was lower in period 1 than in period 2 (15.6% vs. 17.9%;p=0.032). Surgery was the mainstay of treatment before and during the COVID-19 pandemic. Overall, 2,539 and 2,286 women received surgery in period 1 and 2, respectively (93.4% vs. 93.5%;p=0.948). Primary conservative attempts (i.e., progesterone-based therapy) was performed in 72 (2.7%) and 56 (2.3%) patients in period 1 and 2, respectively (p=0.406). The adoption of minimally invasive surgery was consistent in the two study periods (p=0.976). Overall, 1,280 (50.4%) and 1,021 (44.7%) patients had no adjuvant therapy in period 1 and 2, respectively (p<0.001). The adoption of vaginal brachytherapy as adjuvant treatment remained stable in the study periods (11.9% vs. 11.1%;p=0.325). Adjuvant therapies indication has increased during the COVID-19 pandemic (p<0.001). In particular, the use of adjuvant radiotherapy (26.8% vs. 30.7%;p=0.001) and chemotherapy (25.1% vs. 30.1%;p<0.001) alone or in combination increased from period 1 to 2. Conclusion(s): Our data suggest that the COVID-19 pandemic had a significant impact on the characteristics and patterns of care of EC patients. These findings highlight the need to implement healthcare services during the pandemic.
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Background: CSCC is the second most common skin cancer with an estimated incidence of 1 million cases per year in the US. While the surgical cure rate for CSCC is > 95%, some pts have high risk of recurrence as assessed by immune status, primary disease stage, extent of nodal involvement, presence of extracapsular extension (ECE), and prior treatment. Postoperative RT is recommended for these pts but relapse with locoregional recurrence or distant metastases may still occur. C-POST is evaluating the efficacy of cemiplimab as adjuvant therapy for pts with high-risk CSCC. Here, we provide summary of the most recent study protocol amendment. Methods: C-POST is a randomized, placebo-controlled, double-blind, multicenter Phase 3 study to evaluate cemiplimab as adjuvant treatment for pts with high-risk CSCC, based on surgical and clinicopathologic findings, who completed surgery and postoperative RT (minimum total dose 50Gy, within 10 weeks before randomization) (NCT03969004). Pts with at least one of the following high-risk features are eligible: (1) nodal disease with (a) ECE and at least one node ≥20 mm or (b) at least three lymph nodes positive on surgical pathology report, regardless of ECE;(2) in-transit metastases;(3) T4 lesion;(4) perineural invasion;and (5) recurrent CSCC with at least one other risk factor. Pts with CSCC involvement in at least three lymph nodes (feature 1b) were added to the eligibility criteria, as this group was found to be at similar risk of CSCC recurrence as the initially planned study population. Protocol amendment now allows patients with chronic lymphocytic leukemia (CLL) who are not on active treatment to be enrolled. The study has two parts. In Part 1 (blinded), pts are randomly assigned 1:1 to receive cemiplimab 350 mg or placebo intravenously every 3 weeks for 12 weeks, followed by cemiplimab 700 mg or placebo every 6 weeks for 36 weeks. In optional Part 2 (unblinded), pts in the placebo arm who experience disease recurrence and pts in the cemiplimab arm who experience disease recurrence ≥3 months after completion of 48-week treatment in Part 1 are eligible to receive open-label cemiplimab for up to 96 weeks. The trial is expected to enrol 412 pts from about 100 sites in North and South America, Europe, and Asia-Pacific regions. Key primary objective is to compare disease-free survival;secondary objectives include evaluating overall survival, freedom from locoregional relapse, and distant relapse with adjuvant cemiplimab versus placebo in patients with high-risk CSCC. This study is once again open for enrolment following interruptions owing to the COVID-19 pandemic.
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Background: Mammographic screening programmes reduce breast cancer mortality but detect many small tumours with favourable biology which may not progress. These are treated with surgery and adjuvant therapies, but associated morbidities mean there is a need to reduce overtreatment. Minimally invasive treatments such as vacuum-assisted excision (VAE) have been described but there is no prospective randomised evidence to support their routine use. SMALL (ISRCTN 12240119) is designed to establish the feasibility of using VAE to treat small tumours detected within the UK NHS Breast Screening Programme (BSP). Methods: Phase III multicenter randomized trial comparing surgery with VAE for screen-detected good prognosis cancers. Eligibility criteria are age ≥47 years, unifocal grade 1 tumors (maximum diameter 15mm), strongly ER/PR+ve and HER2-ve, with negative axillary staging. Patients are randomized 2:1 to VAE or surgery, with no axillary surgery in the VAE arm. Excision is assessed radiologically, and if incomplete, patients undergo surgery. Adjuvant radiotherapy and endocrine therapy are mandated in the VAE arm. Coprimary end-points are: (1) Non-inferiority comparison of the requirement for a second procedure. (2) Single-arm analysis of local recurrence (LR) at 5 years after VAE. Recruitment of 800 patients will permit demonstration of 10% non-inferiority of VAE for requirement of a second procedure, ensuring sufficient patients for single arm analysis of LR rates, where expected LR free survival is 99% at 5 years, with an undesirable survival probability after VAE of 97%. The DMC will monitor LR events to ensure these do not exceed 3% per year. Secondary outcome measures include time to ipsilateral recurrence, overall survival, complications, quality of life and health economic analysis. A QuinteT Recruitment Intervention (QRI) is integrated throughout SMALL to optimize recruitment and informed consent. Recruitment challenges are identified by analyzing recruiter/ patient interviews, audio-recordings of trial discussions, and by review of screening, eligibility and recruitment data and study documentation. Solutions are developed collaboratively, including recruiter feedback and recruitment tips documents. Results: SMALL opened in December 2019, but recruitment halted for 5 months due to COVID-19. At 11th February 2022, 91 patients had been recruited from 22 centers, with an approached/consented ration of 50%. Drawing from preliminary QRI findings, a recruitment tips document has been circulated (on discussing SMALL, providing balanced information on treatment options and explaining randomization). Individual recruiter feedback has commenced, with wider feedback planned shortly. Conclusion: Despite pandemic-related challenges, SMALL has excellent recruitment to date and is expected to have a global impact on treatment of screen-detected breast cancer.
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Background: During the first year of the COVID-19 pandemic there was global disruption in the provision of healthcare, causing significant pressure on hospital resources. High-grade gliomas (HGG) are rapidly progressive tumors, so patients with delays in diagnosis or treatment due to COVID-19-related disruptions might have poor outcomes. Therefore, we retrospectively evaluated the impact of the COVID- 19 pandemic on treatment patterns and outcomes of patients with HGG in British Columbia (BC). Methods: A case cohort with a pathologic diagnosis of HGG (grade 4 astrocytoma and glioblastoma) treated at BC Cancer centers with radiotherapy between March 1, 2020 - March 1, 2021 (“COVID era”), and a control cohort treated between March 1, 2018 - March 1, 2019 (“pre-COVID era”) were identified. Patient demographics, tumor characteristics, treatment details, and dates of radiographic progression and death were included in the chart review. Analyses were performed with one-way ANOVA and Chi-squared tests for comparisons between eras. The Kaplan-Meier method was used to assess progression-free survival (PFS) and overall survival (OS) and differences in outcome between eras were investigated using the log-rank test. Results: 164 patients were identified: 85 in the pre-COVID era and 79 in the COVID era. There was no statistically significant baseline difference in age, sex, comorbidities, ECOG, tumor diameter, IDH mutation status, or MGMT methylation status between eras. There was also no statistically significant difference between time from symptom onset to first imaging, time from first imaging to surgery, time from surgery to oncologic consultation between eras, and time from surgery to radiotherapy. Significantly more patients were managed with biopsy relative to partial or gross total resection during the COVID era 22% (17/79) than the pre-COVID era 13% (11/85) (p = 0.04). However, radiation treatment (RT) did not differ between eras, with similar rates of conventionally fractionated RT in the pre-COVID era (87%, 74/85) and the COVID era (82%, 65/79) (p = 0.23). Use of concurrent and/or adjuvant temozolomide also was not significantly different between eras (p = 0.27 and p = 0.19, respectively). Median PFS was 7.0 months in both eras (CI95 = 5.5 - 8.5 months for pre-COVID era, CI95 = 5.8 - 8.2 months for COVID era, p = 0.3), and median OS was 13 months in the pre-COVID era (CI95 = 10.3 - 15.7 months) and 16 months in the COVID era (CI95 = 11.5 - 20.5 months), though this difference was not significant (p = 0.09). Conclusions: To our knowledge, this is the first study to assess outcomes of patients treated for HGG during the COVID-19 pandemic. We found that, despite less use of surgery in the COVID era, the outcomes of patients with HGG were not affected.
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The COVID-19 pandemic has opened several new disease scenarios, yielding novel syndromes that have never been seen before and resurrecting old inflammatory phenomena that are no longer recorded, such as radiation recall (RR) syndromes. Radiation recall syndrome is a limited field inflammatory reaction that occurs in a volume that was irradiated several months or years previously before being induced by a triggering factor. The most frequently reported phenomena are skin reactions; however, other organs could be involved, such as the lungs in radiation recall pneumonitis (RRP). It is a well-described inflammatory reaction that occurs within a pulmonary volume that was irradiated several months or years previously via radiotherapy (RT), triggered by factors such as drugs, including chemotherapy agents, immunotherapy, or vaccination. Indeed, during the COVID-19 pandemic, RRP following anti-COVID-19 vaccination or SARS-CoV2 infection was recently reported. ACE receptor-rich tissues such as lung or skin tissues were mainly involved. Herein, we present a case of RRP triggered by COVID-19 pulmonary infection in a woman who previously underwent adjuvant breast cancer radiotherapy. Although symptoms were typical, pulmonary CT findings depicted a unique distribution of ground-glass opacities (GGOs) throughout the previous radiation portals and mirror-like the radiation fields. Anamnesis and radiation plan evaluation were crucial in the diagnosis of RRP.
ABSTRACT
Purpose or Objective Clinical trials are essential to improve cancer treatment. Trials rely on wide-ranging patient (pt) participation to gain adequate sample sizes and externally applicable results. The Danish Breast Cancer Group (DBCG) develops national guidelines for breast cancer therapy, and this is preferably through clinical trials. During 2015-2021 moderately hypofractionated adjuvant loco-regional breast cancer (BC) radiation therapy (RT) was tested in an international trial, the DBCG SKAGEN Trial 1, testing 50Gy/25 fr (standard) versus 40Gy/15fr (experimental). The trial inclusion criteria were broad, thus any pt with indication for loco-regional RT (LR-RT) for unilateral early high-risk BC with no prior cancer and willing/able to participate in the 10-year follow up was a candidate.Recently, the inclusion of pts in trials may have been particularly challenged due to difficulties imposed by the COVID 19 pandemic. Hitherto, the DBCG has had no evidencebased knowledge about trial participation rates (TPR). These are important for evaluating the applicability of the trial results and planning of future RT trials. We present annual trial participation rates during the inclusion period. Materials and Methods The international DBCG SKAGEN Trial 1 randomized patients from 2015 to July 1st 2021, and the 17 participating institutions from 7 countries accrued 2,963 patients. Eight of these institutions accruing 2,184 pts in all delivered data on the total number of pts treated with LR-RT during the inclusion period. We calculated annual TPRs per institution and overall as TPR (number pts enrolled per year/ number pts treated with LR-RT per year). Results From 6,929 pts receiving LR-RT, 2,184 pts were enrolled, corresponding to an overall TPR of 31.5% (figure 1). In all eight institutions, accrual was running from 2016 (figure 2). From 2016, the average single institution TPR per year ranged from 14.4% to 50.4%. Annual TPRs varied with time: most institutions experienced a modest decline in TPR during 2019-2020, while in 2021 TPR seemed to stabilize. In one institution, accrual was terminated during 2020 due to COVID 19 related restrictions.(Figure Presented)(Figure Presented)Conclusion TPRs displayed considerable variation across institutions and time and were vulnerable to COVID 19 related restrictions. Even with a straight-forward trial design and the prospect of a shortened LR-RT course, only one institution succeeded in accruing more than half of the patients likely to be trial candidates. The results indicate, that a TPR around 50% was feasible for the best performing department, thus implying a large potential for better trial accrual in most centres. In future trials, systematic monitoring of TPRs and reasons for not participating should be undertaken to optimize trial designs and accrual procedures
ABSTRACT
INTRODUCTION: High-grade gliomas account for <5% of all pediatric brain tumors with a 20% 5-year overall survival even with maximal safe resection followed by concurrent radiotherapy and chemotherapy. Patients in low-and middle-income countries already face delays and barriers to the treatment they require. The current COVID pandemic has added unique challenges to the delivery of complex, multidisciplinary health services to these patients. METHODOLOGY AND RESULTS: We retrospectively reviewed the records of four patients, ages 2-18 years old, with histologically confirmed high-grade glioma managed in a tertiary government institution from 2020-2021. Three of the patients had a supratentorial tumor and one patient had multiple tumors located in both supra-and infratentorial compartments. Neurosurgical procedures performed were: gross total excision (1), subtotal excision (2), and biopsy (1). The tissue diagnoses obtained were glioblastoma (3) and high-grade astrocytoma (1). Two patients survived and are currently undergoing adjuvant radiotherapy and chemotherapy. The remaining two patients expired: one from hospital-acquired pneumonia and the other from COVID-19 infection. DISCUSSION: Decreased mobility due to lockdowns, the burden of requiring negative COVID-19 results before admission for surgery, reduced hospital capacity to comply with physical distancing measures, the postponement of elective surgery to minimize COVID-19 transmission, physician and nursing shortages due to infection or mandatory isolation of staff, cancellation of face-to-face outpatient clinics, and hesitation among patients and their families to go to the hospital for fear of exposure were found to be common causes of delays in treatment. Also, the redirection of health resources and other government and hospital policies to handle the COVID-19 pandemic resulted in an overall delay in the delivery of health services. In particular, the management of pediatric patients with cancers, especially high-grade gliomas, was significantly disrupted.
ABSTRACT
Objective: NA Background: Glioma classification evolved over the years but remains a diagnostic challenge. Primary spinal cord (PSC) glioblastoma is extremely rare and represents fewer than 1.5% of all spine tumors in adults. Presentation may mimic demyelinating or inflammatory disorders, but prognosis is significantly worse. We present two aggressive cases of extensive, total spinal cord gliomas with early metastases to brain. Design/Methods: NA Case #1: A 44-year-old woman with a diagnosis of demyelinating disorder with paraplegia, bladder and bowel incontinence presented with new appendicular ataxia. Previous MRI revealed unremarkable brain and hyperintensity in T7-10 concerning for multiple sclerosis. Empiric methylprednisolone and cyclophosphamide showed no improvement. Repeat MRI showed extensive intramedullary cystic lesions throughout cervical, thoracic, and lumbar spine, hyperintensities in the brainstem, and enhancing lesions in the corpus callosum and R frontal lobe. Biopsy revealed brain Glioblastoma, WHO grade IV, IDH wildtype. H3K27M test was not performed. Patient expired 13 months after initial symptom onset. Case #2: A 49-year-old man with a recent COVID-19 infection presented with 2 weeks of bilateral lower extremity numbness and weakness. MRI brain was unremarkable, and spine revealed intra-dural, extra-medullary nodular enhancing lesions throughout cervical and thoracic spine, and the cauda equina. Infectious, inflammatory, and rheumatologic causes were investigated until repeat imaging in 1 week (after a course of empiric methylprednisolone) demonstrated the rapid development of a non-enhancing expansile mass in the R temporal lobe. Biopsy revealed spinal Glioblastoma, WHO grade IV, IDH wildtype, negative for H3K27M mutation, and brain low grade glioma. The patient remains on palliative radiation with concurrent temozolomide and adjuvant temozolomide. Conclusions: Primary spinal cord glioblastomas are rare and devastating. Timely diagnosis remains a challenge since clinical and radiographic findings mimic demyelinating or inflammatory disorders. Our cases highlight the diagnostic challenge and importance of early suspicion in the diagnosis of malignant spinal glioma.