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.

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.

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.

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.

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.

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%.

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.

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.

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.

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.

High Concordance and Negative Prognostic Impact of RAS/BRAF/PIK3CA Mutations in Multiple Resected Colorectal Liver Metastases.

BACKGROUND: The prevalence and clinical implications of genetic heterogeneity in patients with multiple colorectal liver metastases remain largely unknown. In a prospective series of patients undergoing resection of colorectal liver metastases, the aim was to investigate the inter-metastatic and primary-to-metastatic heterogeneity of mutations in KRAS, NRAS, BRAF, and PIK3CA and their prognostic impact. PATIENTS AND METHODS: We analyzed the mutation status among 372 liver metastases and 78 primary tumors from 106 patients by methods used in clinical routine testing, by Sanger sequencing, by next-generation sequencing (NGS), and/or by droplet digital polymerase chain reaction. The 3-year cancer-specific survival (CSS) was analyzed using the Kaplan-Meier method. RESULTS: Although Sanger sequencing indicated inter-metastatic mutation heterogeneity in 14 of 97 patients (14%), almost all cases were refuted by high-sensitive NGS. Also, heterogeneity among metastatic deposits was concluded only for PIK3CA in 2 patients. Similarly, primary-to-metastatic heterogeneity was indicated in 8 of 78 patients (10%) using Sanger sequencing but for only 2 patients after NGS, showing the emergence of 1 KRAS and 1 PIK3CA mutation in the metastatic lesions. KRAS mutations were present in 53 of 106 patients (50%) and were associated with poorer 3-year CSS after liver resection (37% vs. 61% for KRAS wild-type; P = .004). Poor prognostic associations were found also for the combination of KRAS/NRAS/BRAF mutations compared with triple wild-type (P = .002). CONCLUSION: Intra-patient mutation heterogeneity was virtually undetected, both between the primary tumor and the liver metastases and among the metastatic deposits. KRAS mutations separately, and KRAS/NRAS/BRAF mutations combined, were associated with poor patient survival after partial liver resection.

High symptom burden is associated with impaired quality of life in colorectal cancer patients during chemotherapy:A prospective longitudinal study.

PURPOSE: Multiple symptoms can have a negative impact on quality of life (QoL), but there is little information about the impact of multiple symptoms on QoL of patients with colorectal cancer (CRC) during outpatient chemotherapy. Therefore, the purpose was to assess the physical and mental QoL in CRC patients over six months of chemotherapy, to evaluate the association of QoL with the presence of multiple symptoms, and to determine which demographic and clinical characteristics are associated with physical and mental QoL scores. METHODS: Outpatients with CRC (N = 120) completed the Medical Outcomes Study Short Form (SF-12) and Memorial Symptom Assessment Scale (MSAS) at eight time points during six months of chemotherapy. Linear mixed models for repeated measures were used to analyse QoL over time; and its association with demographic and clinical characteristics; and with the presence of multiple symptoms (e.g., 'numbness/tingling' and 'problems with sexual interest'). RESULTS: The CRC patients had worse physical and mental QoL scores than the general population at all time points. Impaired physical QoL was significantly associated with psychological symptom burden (p < 0.001) and numbness/tingling (p < 0.027). Impaired mental QoL was associated with physical symptom burden (p < 0.001), with being female (p < 0.009), younger age (p < 0.024), and having problems with sexual interest (p < 0.009). CONCLUSIONS: Impaired QoL was associated with symptoms in CRC outpatients. This information about the symptoms and characteristics associated with worse QoL during chemotherapy may help clinicians identify and inform at-risk patients.

Heterogeneous radiological response to neoadjuvant therapy is associated with poor prognosis after resection of colorectal liver metastases.

INTRODUCTION: Surgery combined with perioperative chemotherapy has become standard of care in patients with resectable colorectal liver metastases. However, poor outcome is expected for a significant subgroup. The clinical implications of inter-metastatic heterogeneity remain largely unknown. In a prospective, population-based series of patients undergoing resection of multiple colorectal liver metastases, the aim was to investigate the prevalence and prognostic impact of heterogeneous response to neoadjuvant chemotherapy. MATERIALS AND METHODS: Radiological response to treatment was evaluated in a lesion-specific manner in 2-5 metastases per patient. Change of lesion diameter was evaluated and response/progression was classified according to three different size thresholds; 3, 4 and 5 mm. A heterogeneous response was defined as progression and response of different metastases in the same patient. RESULTS: In total, 142 patients with 585 liver metastases were examined with the same radiological method (MRI or CT) before and after neoadjuvant treatment. Heterogeneous response to treatment was seen in 16 patients (11%) using the 3 mm size change threshold, and this group had a 5-year cancer-specific survival of 19% compared to 49% for patients with response in all lesions (p = 0.003). Cut-off values of 4-5 mm were less sensitive for detecting a heterogeneous response, but the survival difference was similar and significant. CONCLUSION: A subgroup of patients with multiple colorectal liver metastases had heterogeneous radiological response to neoadjuvant chemotherapy and poor prognosis. The evaluation of response pattern is easy to perform, feasible in clinical practice and, if validated, a promising biomarker for treatment decisions.

Anal cancer chemoradiotherapy outcome prediction using 18F-fluorodeoxyglucose positron emission tomography and clinicopathological factors.

OBJECTIVE: To assess the role of [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET), obtained before and during chemoradiotherapy, in predicting locoregional failure relative to clinicopathological factors for patients with anal cancer. METHODS: 93 patients with anal squamous cell carcinoma treated with chemoradiotherapy were included in a prospective observational study (NCT01937780). FDG-PET/CT was performed for all patients before treatment, and for a subgroup (n = 39) also 2 weeks into treatment. FDG-PET was evaluated with standardized uptake values (SUVmax/peak/mean), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and a proposed Z-normalized combination of MTV and SUVpeak (ZMP). The objective was to predict locoregional failure using FDG-PET, tumor and lymph node stage, gross tumor volume (GTV) and human papilloma virus (HPV) status in univariate and bivariate Cox regression analysis. RESULTS: N3 lymph node stage, HPV negative tumor, GTV, MTV, TLG and ZMP were in univariate analysis significant predictors of locoregional failure (p < 0.01), while SUVmax/peak/mean were not (p > 0.2). In bivariate analysis HPV status was the most independent predictor in combinations with N3 stage, ZMP, TLG, and MTV (p < 0.02). The FDG-PET parameters at 2 weeks into radiotherapy decreased by 30-40 % of the initial values, but neither absolute nor relative decrease improved the prediction models. CONCLUSION: Pre-treatment PET parameters are predictive of chemoradiotherapy outcome in anal cancer, although HPV negativity and N3 stage are the strongest single predictors. Predictions can be improved by combining HPV with PET parameters such as MTV, TLG or ZMP. PET 2 weeks into treatment does not provide added predictive value. ADVANCES IN KNOWLEDGE: Pre-treatment PET parameters of anal cancer showed a predictive role independent of clinicopathological factors. Although the PET parameters show substantial reduction from pre- to mid-treatment, the changes were not predictive of chemoradiotherapy outcome.

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.