Survival prediction in patients with gynecological cancer irradiated for brain metastases.

BACKGROUND AND PURPOSE: This large population-based, retrospective, single-center study aimed to identify prognostic factors in patients with brain metastases (BM) from gynecological cancers. MATERIAL AND METHODS: One hundred and forty four patients with BM from gynecological cancer treated with radiotherapy (RT) were identified. Primary cancer diagnosis, age, performance status, number of BM, presence of extracranial disease, and type of BM treatment were assessed. Overall survival (OS) was calculated using the Kaplan-Meier method and the Cox proportional hazards regression model was used for multivariable analysis. A prognostic index (PI) was developed based on scores from independent predictors of OS. RESULTS: Median OS for the entire study population was 6.2 months. Forty per cent of patients died within 3 months after start of RT. Primary cancer with the origin in cervix or vulva (p = 0.001),  Eastern Cooperative Oncology Group (ECOG) 3-4 (p < 0.001), and the presence of extracranial disease (p = 0.001) were associated with significantly shorter OS. The developed PI based on these factors, categorized patients into three risk groups with a median OS of 13.5, 4.0, and 2.4 months for the good, intermediate, and poor prognosis group, respectively. INTERPRETATION: Patients with BM from gynecological cancers carry a poor prognosis. We identified prognostic factors and developed a scoring tool to select patients with better or worse prognosis. Patients in the high-risk group have a particular poor prognosis, and omission of RT could be considered.

Deep learning-based automatic delineation of anal cancer gross tumour volume: a multimodality comparison of CT, PET and MRI.

BACKGROUND: Accurate target volume delineation is a prerequisite for high-precision radiotherapy. However, manual delineation is resource-demanding and prone to interobserver variation. An automatic delineation approach could potentially save time and increase delineation consistency. In this study, the applicability of deep learning for fully automatic delineation of the gross tumour volume (GTV) in patients with anal squamous cell carcinoma (ASCC) was evaluated for the first time. An extensive comparison of the effects single modality and multimodality combinations of computed tomography (CT), positron emission tomography (PET), and magnetic resonance imaging (MRI) have on automatic delineation quality was conducted. MATERIAL AND METHODS: 18F-fluorodeoxyglucose PET/CT and contrast-enhanced CT (ceCT) images were collected for 86 patients with ASCC. A subset of 36 patients also underwent a study-specific 3T MRI examination including T2- and diffusion-weighted imaging. The resulting two datasets were analysed separately. A two-dimensional U-Net convolutional neural network (CNN) was trained to delineate the GTV in axial image slices based on single or multimodality image input. Manual GTV delineations constituted the ground truth for CNN model training and evaluation. Models were evaluated using the Dice similarity coefficient (Dice) and surface distance metrics computed from five-fold cross-validation. RESULTS: CNN-generated automatic delineations demonstrated good agreement with the ground truth, resulting in mean Dice scores of 0.65-0.76 and 0.74-0.83 for the 86 and 36-patient datasets, respectively. For both datasets, the highest mean Dice scores were obtained using a multimodal combination of PET and ceCT (0.76-0.83). However, models based on single modality ceCT performed comparably well (0.74-0.81). T2W-only models performed acceptably but were somewhat inferior to the PET/ceCT and ceCT-based models. CONCLUSION: CNNs provided high-quality automatic GTV delineations for both single and multimodality image input, indicating that deep learning may prove a versatile tool for target volume delineation in future patients with ASCC.

Colon and rectal cancer survival in seven high-income countries 2010-2014: variation by age and stage at diagnosis (the ICBP SURVMARK-2 project).

OBJECTIVES: As part of the International Cancer Benchmarking Partnership (ICBP) SURVMARK-2 project, we provide the most recent estimates of colon and rectal cancer survival in seven high-income countries by age and stage at diagnosis. METHODS: Data from 386 870 patients diagnosed during 2010-2014 from 19 cancer registries in seven countries (Australia, Canada, Denmark, Ireland, New Zealand, Norway and the UK) were analysed. 1-year and 5-year net survival from colon and rectal cancer were estimated by stage at diagnosis, age and country, RESULTS: (One1-year) and 5-year net survival varied between (77.1% and 87.5%) 59.1% and 70.9% and (84.8% and 90.0%) 61.6% and 70.9% for colon and rectal cancer, respectively. Survival was consistently higher in Australia, Canada and Norway, with smaller proportions of patients with metastatic disease in Canada and Australia. International differences in (1-year) and 5-year survival were most pronounced for regional and distant colon cancer ranging between (86.0% and 94.1%) 62.5% and 77.5% and (40.7% and 56.4%) 8.0% and 17.3%, respectively. Similar patterns were observed for rectal cancer. Stage distribution of colon and rectal cancers by age varied across countries with marked survival differences for patients with metastatic disease and diagnosed at older ages (irrespective of stage). CONCLUSIONS: Survival disparities for colon and rectal cancer across high-income countries are likely explained by earlier diagnosis in some countries and differences in treatment for regional and distant disease, as well as older age at diagnosis. Differences in cancer registration practice and different staging systems across countries may have impacted the comparisons.

Treatment outcomes and prognostic factors after chemoradiotherapy for anal cancer.

BACKGROUND: Squamous cell carcinoma of the anus (SCCA) is a rare malignancy with rising incidence, associated with human papilloma virus (HPV). Chemoradiotherapy (CRT) is the preferred treatment. The purpose was to investigate treatment failure, survival and prognostic factors after CRT. MATERIAL AND METHODS: In this prospective observational study from a large regional centre, 141 patients were included from 2013 to 2017, and 132 were eligible for analysis. The main inclusion criteria were SCCA, planned radiotherapy, and performance status (ECOG) ≤2. Patient characteristics, disease stage, treatment, and treatment response were prospectively registered. Disease-free survival (DFS), overall survival (OS), and locoregional treatment failure after CRT were analysed. Hazard ratios (HRs) were estimated with Cox`s proportional hazards model. RESULTS: Median follow-up was 54 (range 6-71) months. Eighteen patients (14%) had treatment failures after CRT; of these 10 (8%) had residual tumour, and 8 (6%) relapse as first failure. The first treatment failure was locoregional (11 patients), distant (5 patients), and both (2 patients). Salvage abdomino-perineal resection was performed in 10 patients, 2 had resections of metastases, and 3 both. DFS was 85% at 3 years and 78% at 5 years. OS was 93% at 3 years and 86% at 5 years. In analyses adjusted for age and gender, HPV negative tumours (HR 2.5, p = 0.024), N3 disease (HR 2.6, p = 0.024), and tumour size ≥4 cm (HR 2.4, p = 0.038) were negative prognostic factors for DFS. CONCLUSION: State-of-the-art chemoradiotherapy for SCCA resulted in excellent outcomes, and improved survival compared with previous national data, with <15% treatment failures and a 3-year DFS of >80%.

Re-irradiation for recurrent rectal cancer - a single-center experience.

Background: There is no clear consensus on the use of re-irradiation (reRT) in the management of locally recurrent rectal cancer (LRRC). The aim of the present study was to investigate all reRT administered for rectal cancer at a large referral institution and to evaluate patient outcomes and toxicity.Material and methods: All patients with rectal cancer were identified who had received previous pelvic radiotherapy (RT) and underwent reRT during 2006-2016. Medical records and RT details of the primary tumor treatments and rectal cancer recurrence treatments were registered, including details on reRT, chemotherapy, surgery, adverse events, and long-term outcomes.Results: Of 77 patients who received ReRT, 67 had previously received pelvic RT for rectal cancer and were administered reRT for LRRC. Re-irradiation doses were 30.0-45.0 Gy, most often given as hyperfractionated RT in 1.2-1.5 Gy fractions twice daily with concomitant capecitabine. The median time since initial RT was 29 months (range, 13-174 months). Of 36 patients considered as potentially resectable, 20 underwent surgery for LRRC within 3 months after reRT. Operated patients had better 3-year overall survival (OS) (62%) compared to those who were not operated (16%; HR 0.32, p = .001). The median gross tumor volume (GTV) was 107 cm3, and 3-year OS was significantly better in patients with GTV <107 cm3 (44%) compared to patients with GTV ≥107 cm3 (21%; HR 0.52, p = .03).Conclusion: Three-year survival was significantly better for patients who underwent surgery after reRT or who had small tumor volume. Prospective clinical trials are recommended for further improvements in patient selection, outcomes, and toxicity assessment.

Evaluation of the stage classification of anal cancer by the TNM 8th version versus the TNM 7th version.

Background: The UICC TNM 7th edition introduced stage groups for anal cancer which in 2019 has not yet come into general use. The new TNM 8th edition from 2016 defines 7 sub-stages. Background data for these changes are lacking. We aimed to investigate whether the new classification for anal cancer reliably predict the prognosis in the different stages.Patients and methods: The Nordic Anal Cancer Group (NOAC) conducted a large retrospective study of all anal cancers in Norway, Sweden and most of Denmark in 2000-2007. From the Nordic cohort 1151 anal cancer patients with follow-up data were classified by the TNM 4th edition which has identical T, N and M definitions as the TNM 7th edition, and therefore also can be classified by the TNM 7th stage groups. We used the Nordic cohort to translate the T, N and M stages into the TNM 8th stages and sub-stages. Overall survival for each stage was assessed.Results: Although the summary stage groups for TNM 8th edition discriminates patients with different prognosis reasonably well, the analyses of the seven sub-stages show overlapping overall survival: HR for stage IIA 1.30 (95%CI 0.80-2.12) is not significantly different from stage I (p = .30) and HR for stage IIB 2.35 (95%CI 1.40-3.95) and IIIA 2.48 (95%CI 1.43-4.31) are also similar as were HRs for stage IIIB 3.41 (95%CI 1.99-5.85) and IIIC 3.22 (95%CI 1.99-5.20). Similar overlapping was shown for local recurrence and distant spread.Conclusion: The results for the sub-stages calls for a revision of the staging system. We propose a modification of the TNM 8th edition for staging of anal cancer into four stages based on the T, N and M definitions of the TNM 8th classification.

Should calculation of chemotherapy dosage for bowel cancer be based on body composition? / Bør beregning av cellegiftdose ved tarmkreft baseres på kroppssammensetning?

BACKGROUND: Dosage of chemotherapy for colon cancer is currently based on the patient's body surface area. Several studies have identified an association between low fat-free mass and chemotherapy toxicity among patients with metastatic colorectal cancer. This has been less widely studied for localised disease. This review aims to summarise studies that have investigated the association between clinical signs of disease-related malnutrition (low body mass index, weight loss and low muscle mass) and tolerance of chemotherapy in patients with localised colon cancer. MATERIAL AND METHOD: We conducted a systematic search in PubMed with various synonyms of the terms 'colorectal cancer', 'adjuvant chemotherapy', 'nutritional status' and 'toxicity'. The search was concluded in May 2019. Of 553 articles, 39 were considered relevant and read in full text. Ten of these fulfilled the inclusion criteria for this review. RESULTS: Nine of the ten studies indicate an association between clinical signs of disease-related malnutrition and dose-limiting toxicity. The association appears to be especially pronounced in patients with low fat-free mass. INTERPRETATION: The results support the hypothesis that there is an association between disease-related malnutrition and the prevalence of toxicity and modification of the course of adjuvant chemotherapy in patients with localised colon cancer. The potential benefits of basing chemotherapy dosage on body composition in addition to body surface area should be investigated in clinical trials.

Surgical treatment and survival from colorectal cancer in Denmark, England, Norway, and Sweden: a population-based study.

BACKGROUND: Survival from colorectal cancer has been shown to be lower in Denmark and England than in comparable high-income countries. We used data from national colorectal cancer registries to assess whether differences in the proportion of patients receiving resectional surgery could contribute to international differences in colorectal cancer survival. METHODS: In this population-based study, we collected data from all patients aged 18-99 years diagnosed with primary, invasive, colorectal adenocarcinoma from Jan 1, 2010, to Dec 31, 2012, in Denmark, England, Norway, and Sweden, from national colorectal cancer registries. We estimated age-standardised net survival using multivariable modelling, and we compared the proportion of patients receiving resectional surgery by stage and age. We used logistic regression to predict the resectional surgery status patients would have had if they had been treated as in the best performing country, given their individual characteristics. FINDINGS: We extracted registry data for 139 457 adult patients with invasive colorectal adenocarcinoma: 12 958 patients in Denmark, 97 466 in England, 11 450 in Norway, and 17 583 in Sweden. 3-year colon cancer survival was lower in England (63·9%, 95% CI 63·5-64·3) and Denmark (65·7%, 64·7-66·8) than in Norway (69·5%, 68·4-70·5) and Sweden (72·1%, 71·2-73·0). Rectal cancer survival was lower in England (69·7%, 69·1-70·3) than in the other three countries (Denmark 72·5%, 71·1-74·0; Sweden 74·1%, 72·7-75·4; and Norway 75·0%, 73·1-76·8). We found no significant differences in survival for patients with stage I disease in any of the four countries. 3-year survival after stage II or III rectal cancer and stage IV colon cancer was consistently lower in England (stage II rectal cancer 86·4%, 95% CI 85·0-87·6; stage III rectal cancer 75·5%, 74·2-76·7; and stage IV colon cancer 20·5%, 19·9-21·1) than in Norway (94·1%, 91·5-96·0; 83·4%, 80·1-86·1; and 33·0%, 31·0-35·1) and Sweden (92·9%, 90·8-94·6; 80·6%, 78·2-82·7; and 23·7%, 22·0-25·3). 3-year survival after stage II rectal cancer and stage IV colon cancer was also lower in England than in Denmark (stage II rectal cancer 91·2%, 88·8-93·1; and stage IV colon cancer 23·5%, 21·9-25·1). The total proportion of patients treated with resectional surgery ranged from 47 803 (68·4%) of 69 867 patients in England to 9582 (81·3%) of 11 786 in Sweden for colon cancer, and from 16 544 (59·9%) of 27 599 in England to 4106 (70·8%) of 5797 in Sweden for rectal cancer. This range was widest for patients older than 75 years (colon cancer 19 078 [59·7%] of 31 946 patients in England to 4429 [80·9%] of 5474 in Sweden; rectal cancer 4663 [45·7%] of 10 195 in England to 1342 [61·9%] of 2169 in Sweden), and the proportion of patients treated with resectional surgery was consistently lowest in England. The age gradient of the decline in the proportion of patients treated with resectional surgery was steeper in England than in the other three countries in all stage categories. In the hypothetical scenario where all patients were treated as in Sweden, given their age, sex, and disease stage, the largest increase in resectional surgery would be for patients with stage III rectal cancer in England (increasing from 70·3% to 88·2%). INTERPRETATION: Survival from colon cancer and rectal cancer in England and colon cancer in Denmark was lower than in Norway and Sweden. Survival paralleled the relative provision of resectional surgery in these countries. Differences in patient selection for surgery, especially in patients older than 75 years or individuals with advanced disease, might partly explain these differences in international colorectal cancer survival. FUNDING: Early Diagnosis Policy Research Grant from Cancer Research UK (C7923/A18348).

Symptoms during chemotherapy in colorectal cancer patients.

PURPOSE: Colorectal cancer (CRC) patients experience several physical and psychological co-occurring symptoms, but little is known about symptom variation during chemotherapy cycles. Therefore, the aims were (1) to assess the occurrence and severity of frequently occurring symptoms (worrying, lack of energy, numbness/tingling, nausea, and pain) at multiple time points during chemotherapy, (2) to investigate differences in symptom trajectories between chemotherapy groups, and (3) to determine whether selected patient and clinical characteristics are associated with symptom severity throughout the treatment trajectory. METHODS: In total, 120 CRC patients receiving chemotherapy with curative or palliative intent completed the Memorial Symptom Assessment Scale (MSAS), Self-Administered Comorbidity Questionnaire (SCQ-19), and Karnofsky Performance Status (KPS) scale eight times, during two cycles of chemotherapy and 3 and 6 months after enrolment. Data were analyzed using linear mixed models for repeated measures to assess the effects of selected variables on outcomes over time. RESULTS: The patients experienced greatest symptom severity in the days following the administration of chemotherapy; these were lack of energy, numbness/tingling (oxaliplatin group), and nausea. Palliative patients reported significantly higher pain scores compared with curative patients over time, whereas the severity of worrying decreased over time in both treatment groups. Age, sex, educational level, performance status, treatment intent and type of chemotherapy were significantly associated with symptom severity throughout the chemotherapy trajectory. CONCLUSION: Clinicians can use these findings to identify and inform patients about risk for more severe symptom burden, in order to offer supportive care at the right time during the chemotherapy treatment.

Patient factors and quality of life outcomes differ among four subgroups of oncology patients based on symptom occurrence.

CONTEXT: Reviews of the literature on symptoms in oncology patients undergoing curative treatment, as well as patients receiving palliative care, suggest that they experience multiple, co-occurring symptoms and side effects. OBJECTIVES: The purposes of this study were to determine if subgroups of oncology patients could be identified based on symptom occurrence rates and if these subgroups differed on a number of demographic and clinical characteristics, as well as on quality of life (QoL) outcomes. METHODS: Latent class analysis (LCA) was used to identify subgroups (i.e. latent classes) of patients with distinct symptom experiences based on the occurrence rates for the 13 most common symptoms from the Memorial Symptom Assessment Scale. RESULTS: In total, 534 patients with breast, head and neck, colorectal, or ovarian cancer participated. Four latent classes of patients were identified based on probability of symptom occurrence: all low class [i.e. low probability for all symptoms (n = 152)], all high class (n = 149), high psychological class (n = 121), and low psychological class (n = 112). Patients in the all high class were significantly younger compared with patients in the all low class. Furthermore, compared to the other three classes, patients in the all high class had lower functional status and higher comorbidity scores, and reported poorer QoL scores. Patients in the high and low psychological classes had a moderate probability of reporting physical symptoms. Patients in the low psychological class reported a higher number of symptoms, a lower functional status, and poorer physical and total QoL scores. CONCLUSION: Distinct subgroups of oncology patients can be identified based on symptom occurrence rates. Patient characteristics that are associated with these subgroups can be used to identify patients who are at greater risk for multiple co-occurring symptoms and diminished QoL, so that these patients can be offered appropriate symptom management interventions.

Is England closing the international gap in cancer survival?

BACKGROUND: We provide an up-to-date international comparison of cancer survival, assessing whether England is 'closing the gap' compared with other high-income countries. METHODS: Net survival was estimated using national, population-based, cancer registrations for 1.9 million patients diagnosed with a cancer of the stomach, colon, rectum, lung, breast (women) or ovary in England during 1995-2012. Trends during 1995-2009 were compared with estimates for Australia, Canada, Denmark, Norway and Sweden. Clinicians were interviewed to help interpret trends. RESULTS: Survival from all cancers remained lower in England than in Australia, Canada, Norway and Sweden by 2005-2009. For some cancers, survival improved more in England than in other countries between 1995-1999 and 2005-2009; for example, 1-year survival from stomach, rectal, lung, breast and ovarian cancers improved more than in Australia and Canada. There has been acceleration in lung cancer survival improvement in England recently, with average annual improvement in 1-year survival rising to 2% during 2010-2012. Survival improved more in Denmark than in England for rectal and lung cancers between 1995-1999 and 2005-2009. CONCLUSIONS: Survival has increased in England since the mid-1990s in the context of strategic reform in cancer control, however, survival remains lower than in comparable developed countries and continued investment is needed to close the international survival gap.

Palliative pelvic radiotherapy of symptomatic incurable rectal cancer - a systematic review.

BACKGROUND: Locally advanced and recurrent rectal cancers frequently cause pelvic morbidity including pain, bleeding and mass effect. Palliative pelvic radiotherapy is used to relieve these symptoms and delay local progression. There is no established optimal radiotherapy regimen and clinical practices vary. Our aim was to review the efficacy and toxicity of palliative pelvic radiotherapy of symptomatic rectal cancer and to evaluate different fractionation schedules, based on published literature. MATERIAL AND METHODS: Systematic literature searches of Medline, Embase and Cochrane databases were performed through 2011. Studies reporting symptomatic response or quality of life (QOL) after palliative radiotherapy for rectal or rectosigmoid cancer were eligible. Results. Twenty-seven studies were included, of which 23 were retrospective reviews. There were no patient-reported outcomes or QOL assessments. There were large variations in applied radiotherapy regimens. Pooled overall symptom response rate was 75% and positive responses were reported for pain (78%), bleeding and discharge (81%), mass effect (71%) and other pelvic symptoms (72%). Toxicity results were not evaluable. CONCLUSION: Palliative pelvic radiotherapy for symptomatic rectal cancer appears to provide relief of a variety of pelvic symptoms, although there is no documented optimal radiotherapy regimen in this context. There is inadequate evidence regarding onset, duration and degree of symptom palliation, QOL and associated toxicity with this treatment and prospective studies are therefore needed.

Patient-reported outcomes evaluating palliative radiotherapy and chemotherapy in patients with oesophageal cancer: a systematic review.

BACKGROUND: Patient-reported outcomes (PROs) and assessments of treatment-related toxicity provide important information on the effect of palliative chemotherapy and/or radiotherapy. The aim of this study was to review the effect of palliative radiotherapy and/or chemotherapy on symptoms and quality of life assessed by PROs and measurement of toxicity for patients with oesophageal cancer. METHODS: The Central, Medline and Embase databases (1990 to November 2011) were systematically searched for prospective studies of palliative chemotherapy and/or radiotherapy in patients with advanced oesophageal cancer with PRO- and/or toxicity outcomes. The risks of bias were assessed. RESULTS: Of 2677 records identified, only 32 included PROs, of which eight were randomised controlled trials. In studies with sufficient standard of PRO (n = 18), either Health Related Quality of Life (HRQL) (n = 14) or patient-reported dysphagia (n = 4), were assessed. Docetaxel added to cisplatin + fluorouracil (CF) improved HRQL compared to CF only, even though toxicity increased. Epirubicin added to CF resulted in longer preserved HRQL than its comparator in two trials, and non-inferiority in one. All phase II chemotherapy studies reported maintained HRQL or improved dysphagia combined with low level of toxicity. Brachytherapy resulted in better HRQL compared to stent placement in two trials, and external radiotherapy relieved dysphagia. The quality of the HRQL methodology and the interpretation and presentation of the PRO results varied, and clinical significance was seldom discussed. CONCLUSION: PRO endpoints are seldom used and further studies of homogenous patient groups with valid measures and methodology of PROs should be encouraged in the evaluation of palliative treatment. Brachytherapy, external radiotherapy and combination chemotherapy improved HRQL and dysphagia in the few identified studies with sufficient PRO methodology.

Impaired health-related quality of life after chemoradiotherapy for anal cancer: late effects in a national cohort of 128 survivors.

BACKGROUND: Chemoradiotherapy is an effective treatment for anal cancer, yet from follow-up many survivors seem to suffer from late effects. Data of long-term health-related quality of life (HRQOL) in anal cancer survivors are limited, and there is a growing interest in cancer survivorship. MATERIAL AND METHODS: A national cohort of all anal cancer survivors treated with curative chemoradiotherapy in 2000-2007 was invited to a cross-sectional study. Of 199 eligible survivors, 128 (64%) returned the questionnaires, the median time since diagnosis was 66 months. The median age was 61 years and 79% were women. HRQOL was evaluated with EORTC questionnaires QLQ-C30 and QLQ-CR29, and neurotoxicity with the Scale of Chemotherapy-Induced Neurotoxicity. An age- and sex-matched reference group of volunteers (n = 269) not treated for pelvic cancer answered the same questionnaires. Results from QLQ-C30 of the reference group were compared to Norwegian and Dutch normative data. RESULTS: The mean scores of anal cancer survivors were poorer compared to volunteers and normative data. Anal cancer survivors reported significant impairment of function, especially social and role function, compared to the volunteers (difference ≥ 20 points, p < 0.001). Survivors had markedly increased scores for fatigue, dyspnoea, insomnia and diarrhoea (difference ≥ 15 points, p < 0.001). The global quality of life was significantly reduced (difference 15 points, p < 0.001). Anal cancer survivors had increased stool frequency, more buttock pain, flatulence, faecal incontinence, impotence (males), dyspareunia and reduced sexual interest (females) (difference ≥ 15 points, p < 0.001). There was increased frequency of tinnitus in survivors treated with cisplatin-based chemotherapy (p = 0.004). CONCLUSIONS: Survivors after chemoradiotherapy for anal cancer have significant long-term impairment of HRQOL. Reduced social, role and sexual function, and increased diarrhoea, incontinence for gas and stools, and buttock pain were commonly reported. Increased awareness of this may lead to better management of late effects and better care for cancer survivors.

Stability of metabolic tumor volume may enable radiotherapy dose painting in anal cancer.

PURPOSE: To evaluate the variability of the 18F-FDG-PET/CT-based metabolic tumor volume (MTV) in anal cancers during fractionated chemoradiotherapy (CRT), and assess the impact of this variability on dosimetric accuracy in MTV-targeted dose painting. METHODS: Eleven patients with anal squamous cell carcinoma who received fractionated chemoradiotherapy with curative intent were included. 18F-FDG PET/CT images were acquired at pre- and mid-treatment. Target volumes and organs at risk (OARs) were contoured manually on both image series. The MTV was generated from the PET images by thresholding. Treatment plans were retrospectively optimized for both image series using volumetric modulated arc therapy (VMAT). Standard plans prescribed 48.6 Gy, 54 Gy and 57.5 Gy in 27 fractions to elective regions, lymph node metastases and primary tumor, respectively. Dose painting plans included an extra dose level of 65 Gy to the MTV. Pre-treatment plans were transferred and re-calculated at mid-treatment basis. RESULTS: MTV decreased from pre- to mid-treatment in 10 of the 11 patients. On average, 71 % of MTVmid overlapped with MTVpre. The median and mean doses to the MTV were robust against anatomical changes, but the transferred dose painting plans had lower D98% values than the original and re-optimized plans. No major differences were found between standard and dose painting plans for OARs. CONCLUSIONS: Despite volumetric changes in the MTV, adequate dose coverage was observed in most dose painting plans. The findings indicate little or no need for adaptive dose painting at mid-treatment. Dose painting appears to be a safe treatment alternative with similar dose sparing of OARs.

Development and validation of prognostic models for anal cancer outcomes using distributed learning: protocol for the international multi-centre atomCAT2 study.

BACKGROUND: Anal cancer is a rare cancer with rising incidence. Despite the relatively good outcomes conferred by state-of-the-art chemoradiotherapy, further improving disease control and reducing toxicity has proven challenging. Developing and validating prognostic models using routinely collected data may provide new insights for treatment development and selection. However, due to the rarity of the cancer, it can be difficult to obtain sufficient data, especially from single centres, to develop and validate robust models. Moreover, multi-centre model development is hampered by ethical barriers and data protection regulations that often limit accessibility to patient data. Distributed (or federated) learning allows models to be developed using data from multiple centres without any individual-level patient data leaving the originating centre, therefore preserving patient data privacy. This work builds on the proof-of-concept three-centre atomCAT1 study and describes the protocol for the multi-centre atomCAT2 study, which aims to develop and validate robust prognostic models for three clinically important outcomes in anal cancer following chemoradiotherapy. METHODS: This is a retrospective multi-centre cohort study, investigating overall survival, locoregional control and freedom from distant metastasis after primary chemoradiotherapy for anal squamous cell carcinoma. Patient data will be extracted and organised at each participating radiotherapy centre (n = 18). Candidate prognostic factors have been identified through literature review and expert opinion. Summary statistics will be calculated and exchanged between centres prior to modelling. The primary analysis will involve developing and validating Cox proportional hazards models across centres for each outcome through distributed learning. Outcomes at specific timepoints of interest and factor effect estimates will be reported, allowing for outcome prediction for future patients. DISCUSSION: The atomCAT2 study will analyse one of the largest available cross-institutional cohorts of patients with anal cancer treated with chemoradiotherapy. The analysis aims to provide information on current international clinical practice outcomes and may aid the personalisation and design of future anal cancer clinical trials through contributing to a better understanding of patient risk stratification.

Treatment of Squamous Cell Carcinoma of the Anus, Unresolved Areas and Future Perspectives for Research: Perspectives of Research Needs in Anal Cancer.

Anal cancer is a relatively rare, mostly HPV-related cancer. The curative treatment consists of concurrent chemoradiation delivered with modern radiotherapy techniques. The prognosis for most patients with early localized disease is very favourable; however patients with locally advanced disease and/or HPV negative tumours are at higher risk of locoregional and distant treatment failure. Tailored approaches are presently being investigated to determine the most suitable regimen in terms of radiotherapy dose prescription, target volume selection, normal tissue avoidance, and combination therapy. Metastatic anal cancer is treated with chemotherapy aiming at prolonged survival. The role of immune therapy in the clinical setting is being investigated. There is little knowledge on the biology of anal cancer, and an urgent need for more clinical and translational research dedicated to this disease. In this article, the evidence-base for the current treatment is briefly reviewed, and perspectives on future research needs are high-lighted.

Predicting outcomes in anal cancer patients using multi-centre data and distributed learning - A proof-of-concept study.

BACKGROUND AND PURPOSE: Predicting outcomes is challenging in rare cancers. Single-institutional datasets are often small and multi-institutional data sharing is complex. Distributed learning allows machine learning models to use data from multiple institutions without exchanging individual patient-level data. We demonstrate this technique in a proof-of-concept study of anal cancer patients treated with chemoradiotherapy across multiple European countries. MATERIALS AND METHODS: atomCAT is a three-centre collaboration between Leeds Cancer Centre (UK), MAASTRO Clinic (The Netherlands) and Oslo University Hospital (Norway). We trained and validated a Cox proportional hazards regression model in a distributed fashion using data from 281 patients treated with radical, conformal chemoradiotherapy for anal cancer in three institutions. Our primary endpoint was overall survival. We selected disease stage, sex, age, primary tumour size, and planned radiotherapy dose (in EQD2) a priori as predictor variables. RESULTS: The Cox regression model trained across all three centres found worse overall survival for high risk disease stage (HR = 2.02), male sex (HR = 3.06), older age (HR = 1.33 per 10 years), larger primary tumour volume (HR = 1.05 per 10 cm3) and lower radiotherapy dose (HR = 1.20 per 5 Gy). A mean concordance index of 0.72 was achieved during validation, with limited variation between centres (Leeds = 0.72, MAASTRO = 0.74, Oslo = 0.70). The global model performed well for risk stratification for two out of three centres. CONCLUSIONS: Using distributed learning, we accessed and analysed one of the largest available multi-institutional cohorts of anal cancer patients treated with modern radiotherapy techniques. This demonstrates the value of distributed learning in outcome modelling for rare cancers.

Common and distinct characteristics associated with self-reported functional status in older patients with cancer receiving chemotherapy.

PURPOSE: To evaluate for inter-individual differences in two subjective measures of functional status in older patients (n = 112), as well as to determine which demographic, clinical, and symptom characteristics, and levels of cognitive function, were associated with initial levels and with the trajectory of the two measures. METHODS: Functional status was assessed using self-report measures of physical function (PF) and role function (RF) from the European Organization for Research and Treatment of Cancer Core Quality-of-Life Questionnaire at the initiation of chemotherapy and at 1, 3, 6, 9, and 12 months after its initiation. Hierarchical linear modeling was used to assess inter-individual differences in and characteristics associated with initial levels and changes in PF and RF. RESULTS: Characteristics associated with decreases in PF at the initiation of chemotherapy were higher numbers of comorbidities and higher depression, pain, and dyspnea scores. For initial levels of poorer RF, lower Karnofsky Performance Status scores and higher pain and fatigue scores were the associated characteristics. Characteristic associated with worse trajectories of PF was not having had surgery. For RF, worse trajectories were associated with lower cognitive function and higher RF at enrollment. Characteristic associated with both lower initial levels and improved trajectories of PF was having lower performance status at enrollment. CONCLUSIONS: Older patients undergoing chemotherapy experience reduced functional performance. Characteristics associated with decrements in PF and RF need to be assessed and interventions implemented to maintain and increase functional status in older oncology patients.

[How do Norwegian oncologists perceive their working conditions?]. / Hva mener norske onkologer om sin arbeidssituasjon?

BACKGROUND: After receiving worrying signals from its members concerning their workload, the Norwegian Oncology Society decided to review how Norwegian oncologists perceive their working conditions. MATERIAL AND METHODS: A questionnaire was sent to all doctors working in departments of oncology. They were asked to provide background information about themselves, how they experienced the working conditions, and what could be done to improve work satisfaction. Descriptive statistics were used for analysis of results. RESULTS: 174 of 298 doctors (58 %) answered the questionnaire. The median number of working hours per week was 52 hours for oncologists, and 45 hours for doctors in training. 72 % of oncologists and 56 % of doctors in training stated the workload is so high that it is difficult to complete all tasks. 63 % of oncologists felt that work was so energy-consuming that it affected their private life, 77 % of them were quite dissatisfied or very dissatisfied with time allocated to do research. 54 % of specialists and 72 % of doctors in training were very happy or happy with their job in general. 86 % of specialists and 61 % of doctors in training reported that more positions for oncologists and doctors in training, respectively, would increase their job satisfaction. INTERPRETATION: Doctors working in the field of oncology in Norway regard the workload to be too high. Oncologists believe that job satisfaction would improve if more time was allocated to research and if there were more positions for doctors at all levels.