ABSTRACT
BACKGROUND: Pre-operative chemoradiotherapy (CRT) rather than radiotherapy (RT) has resulted in fewer locoregional recurrences (LRRs), but no decrease in distant metastasis (DM) rate for patients with locally advanced rectal cancer (LARC). In many countries, patients receive post-operative chemotherapy (pCT) to improve oncological outcomes. We investigated the value of pCT after pre-operative CRT in the RAPIDO trial. PATIENTS AND METHODS: Patients were randomised between experimental (short-course RT, chemotherapy and surgery) and standard-of-care treatment (CRT, surgery and pCT depending on hospital policy). In this substudy, we compared curatively resected patients from the standard-of-care group who received pCT (pCT+ group) with those who did not (pCT- group). Subsequently, patients from the pCT+ group who received at least 75% of the prescribed chemotherapy cycles (pCT ≥75% group) were compared with patients who did not receive pCT (pCT-/- group). By propensity score stratification (PSS), we adjusted for the following unbalanced confounders: age, clinical extramural vascular invasion, distance to the anal verge, ypT stage, ypN stage, residual tumour, serious adverse event (SAE) and/or readmission within 6 weeks after surgery and SAE related to pre-operative CRT. Cumulative probability of disease-free survival (DFS), DM, LRR and overall survival (OS) was analysed by Cox regression. RESULTS: In total, 396/452 patients had a curative resection. The number of patients in the pCT+, pCT >75%, pCT- and pCT-/- groups was 184, 112, 154 and 149, respectively. The PSS-adjusted analyses for all endpoints demonstrated hazard ratios between approximately 0.7 and 0.8 (pCT+ versus pCT-), and 0.5 and 0.8 (pCT ≥75% versus pCT-/-). However, all 95% confidence intervals included 1. CONCLUSIONS: These data suggest a benefit of pCT after pre-operative CRT for patients with high-risk LARC, with approximately 20%-25% improvement in DFS and OS and 20%-25% risk reductions in DM and LRR. Compliance with pCT additionally reduces or improves all endpoints by 10%-20%. However, differences are not statistically significant.
Subject(s)
Rectal Neoplasms , Humans , Infant , Rectal Neoplasms/drug therapy , Neoadjuvant Therapy/methods , Neoplasm Recurrence, Local/drug therapy , Chemoradiotherapy/methods , Disease-Free SurvivalABSTRACT
BACKGROUND: Capecitabine- or 5-fluorouracil (5-FU)-based chemotherapy is widely used in many solid tumours, but is associated with cardiotoxicity. S-1 is a fluoropyrimidine with low rates of cardiotoxicity, but evidence regarding the safety of switching to S-1 after 5-FU- or capecitabine-associated cardiotoxicity is scarce. PATIENTS AND METHODS: This retrospective study (NCT04260269) was conducted at 13 centres in 6 countries. The primary endpoint was recurrence of cardiotoxicity after switch to S-1-based treatment due to 5-FU- or capecitabine-related cardiotoxicity: clinically meaningful if the upper boundary of the 95% confidence interval (CI; by competing risk) is not including 15%. Secondary endpoints included cardiac risk factors, diagnostic work-up, treatments, outcomes, and timelines of cardiotoxicity. RESULTS: Per protocol, 200 patients, treated between 2011 and 2020 [median age 66 years (range 19-86); 118 (59%) males], were included. Treatment intent was curative in 145 (73%). Initial cardiotoxicity was due to capecitabine (n = 170), continuous infusion 5-FU (n = 22), or bolus 5-FU (n = 8), which was administered in combination with other chemotherapy, targeted agents, or radiotherapy in 133 patients. Previous cardiovascular comorbidities were present in 99 (50%) patients. Cardiotoxic events (n = 228/200) included chest pain (n = 125), coronary syndrome/infarction (n = 69), arrhythmia (n = 22), heart failure/cardiomyopathy (n = 7), cardiac arrest (n = 4), and malignant hypertension (n = 1). Cardiotoxicity was severe or life-threatening in 112 (56%) patients and led to permanent capecitabine/5-FU discontinuation in 192 (96%). After switch to S-1, recurrent cardiotoxicity was observed in eight (4%) patients (95% CI 2.02-7.89, primary endpoint met). Events were limited to grade 1-2 and occurred at a median of 16 days (interquartile range 7-67) from therapy switch. Baseline ischemic heart disease was a risk factor for recurrent cardiotoxicity (odds ratio 6.18, 95% CI 1.36-28.11). CONCLUSION: Switching to S-1-based therapy is safe and feasible after development of cardiotoxicity on 5-FU- or capecitabine-based therapy and allows patients to continue their pivotal fluoropyrimidine-based treatment.
Subject(s)
Fluorouracil , Neoplasms , Adult , Aged , Aged, 80 and over , Capecitabine/adverse effects , Cardiotoxicity/etiology , Female , Fluorouracil/adverse effects , Humans , Male , Middle Aged , Neoplasms/drug therapy , Retrospective Studies , Young AdultABSTRACT
BACKGROUND: Prediction models are useful tools in the clinical management of colon cancer patients, particularly when estimating the recurrence rate and, thus, the need for adjuvant treatment. However, the most used models (MSKCC, ACCENT) are based on several decades-old patient series from clinical trials, likely overestimating the current risk of recurrence, especially in low-risk groups, as outcomes have improved over time. The aim was to develop and validate an updated model for the prediction of recurrence within 5 years after surgery using routinely collected clinicopathologic variables. MATERIAL AND METHODS: A population-based cohort from the Swedish Colorectal Cancer Registry of 16,134 stage I-III colon cancer cases was used. A multivariable model was constructed using Cox proportional hazards regression. Three-quarters of the cases were used for model development and one quarter for internal validation. External validation was performed using 12,769 stage II-III patients from the Norwegian Colorectal Cancer Registry. The model was compared to previous nomograms. RESULTS: The nomogram consisted of eight variables: sex, sidedness, pT-substages, number of positive and found lymph nodes, emergency surgery, lymphovascular and perineural invasion. The area under the curve (AUC) was 0.78 in the model, 0.76 in internal validation, and 0.70 in external validation. The model calibrated well, especially in low-risk patients, and performed better than existing nomograms in the Swedish registry data. The new nomogram's AUC was equal to that of the MSKCC but the calibration was better. CONCLUSION: The nomogram based on recently operated patients from a population registry predicts recurrence risk more accurately than previous nomograms. It performs best in the low-risk groups where the risk-benefit ratio of adjuvant treatment is debatable and the need for an accurate prediction model is the largest.
Subject(s)
Colonic Neoplasms , Neoplasm Recurrence, Local , Area Under Curve , Cohort Studies , Colonic Neoplasms/epidemiology , Colonic Neoplasms/pathology , Humans , Neoplasm Recurrence, Local/epidemiology , Neoplasm Staging , Nomograms , Retrospective StudiesABSTRACT
PURPOSE: This study evaluated the effects of coping skills training (CST) on symptoms of depression and anxiety in cancer patients, and investigated moderators of the effects. METHODS: Overall effects and intervention-related moderators were studied in meta-analyses of pooled aggregate data from 38 randomized controlled trials (RCTs). Patient-related moderators were examined using linear mixed-effect models with interaction tests on pooled individual patient data (n = 1953) from 15 of the RCTs. RESULTS: CST had a statistically significant but small effect on depression (g = -0.31,95% confidence interval (CI) = -0.40;-0.22) and anxiety (g = -0.32,95%CI = -0.41;-0.24) symptoms. Effects on depression symptoms were significantly larger for interventions delivered face-to-face (p = .003), led by a psychologist (p = .02) and targeted to patients with psychological distress (p = .002). Significantly larger reductions in anxiety symptoms were found in younger patients (pinteraction < 0.025), with the largest reductions in patients <50 years (ß = -0.31,95%CI = -0.44;-0.18) and no significant effects in patients ≥70 years. Effects of CST on depression (ß = -0.16,95%CI = -0.25;-0.07) and anxiety (ß = -0.24,95%CI = -0.33;-0.14) symptoms were significant in patients who received chemotherapy but not in patients who did not (pinteraction < 0.05). CONCLUSIONS: CST significantly reduced symptoms of depression and anxiety in cancer patients, and particularly when delivered face-to-face, provided by a psychologist, targeted to patients with psychological distress, and given to patients who were younger and received chemotherapy.
Subject(s)
Adaptation, Psychological , Anxiety/therapy , Depression/therapy , Neoplasms/psychology , Patient Education as Topic/methods , Adult , Aged , Female , Humans , Male , Middle Aged , Quality of Life , Randomized Controlled Trials as TopicABSTRACT
BACKGROUND: The optimal timing of surgery for rectal cancer after radiotherapy (RT) is disputed. The Stockholm III trial concluded that it was oncologically safe to delay surgery for 4-8 weeks after short-course RT (SRT), with fewer postoperative complications compared with SRT with surgery within a week. Other studies have indicated that an even shorter interval between RT and surgery (0-3 days) might be beneficial. The aim of this study was to identify the optimal interval to surgery after RT. METHODS: Patients were analysed as treated, in terms of overall treatment time (OTT), the interval from the start of RT until the day of surgery. Patients receiving SRT (5 × 5 Gy) were categorized according to OTT: 7 days (group A), 8-13 days (group B), 5-7 weeks (group C) and 8-13 weeks (group D). Patients receiving long-course RT (25 × 2 Gy) were grouped into those with an OTT of 9-11 weeks (group E) or 12-14 weeks (group F). Outcomes assessed were postoperative complications and early mortality. RESULTS: A total of 810 patients were analysed (group A, 100; group B, 247; group C, 192; group D, 160; group E, 52; group F, 59). Baseline patient characteristics were similar. There were significantly more overall complications in group B than in groups C and D. Adjusted odds ratios, with B as the reference group, were: 0·72 (95 per cent c.i. 0·40 to 1·32; P = 0·289), 0·50 (0·30 to 0·84; P = 0·009) and 0·39 (0·23 to 0·65; P < 0·001) for groups A, C and D respectively. Early mortality was similar in all groups. There were no significant differences between long-course RT groups. CONCLUSION: These results suggest that surgery should optimally be delayed for 4-12 weeks (OTT 5-13 weeks) after SRT.
Subject(s)
Neoadjuvant Therapy , Postoperative Complications/etiology , Rectal Neoplasms/therapy , Aged , Female , Humans , Male , Middle Aged , Neoadjuvant Therapy/adverse effects , Postoperative Complications/epidemiology , Rectal Neoplasms/mortality , Rectal Neoplasms/radiotherapy , Rectal Neoplasms/surgery , Risk Factors , Time FactorsABSTRACT
BACKGROUND: Metastatic colorectal cancer (mCRC) is a heterogeneous disease where prognosis is dependent both on tumor biology and host factors. Total circulating cell-free DNA (cfDNA) has shown to harbor prognostic information in mCRC, although less is known about the biological correlates of cfDNA levels in this patient group. The primary objective was to evaluate the prognostic value of pretreatment cfDNA in patients receiving the first-line oxaliplatin-based chemotherapy for mCRC, by using a predefined upper limit of normal (ULN) from a cohort of presumed healthy individuals. The secondary objective was to model cfDNA levels as a function of predefined tumor and host factors. PATIENTS AND METHODS: This was a retrospective post hoc study based on a prospective multicenter phase III trial, the NORDIC-VII study. DNA was purified from 547 plasma samples and cfDNA quantified by a droplet digital PCR assay (B2M, PPIA) with controls for lymphocyte contamination. Main clinical end point was overall survival (OS). RESULTS: cfDNA was quantified in 493 patients, 54 were excluded mainly due to lymphocyte contamination. Median cfDNA level was 7673 alleles/ml (1050-1 645 000) for B2M and 5959 alleles/ml (555-854 167) for PPIA. High cfDNA levels were associated with impaired outcome; median OS of 16.6 months for levels above ULN and 25.9 months for levels below ULN (hazard ratio = 1.83, 95% confidence interval 1.51-2.21, P < 0.001). The result was confirmed in multivariate OS analysis adjusting for established clinicopathological characteristics. A linear regression model predicted cfDNA levels from sum of longest tumor diameters by RECIST, the presence of liver metastases and systemic inflammatory response as measured by interleukin 6 (F(6, 357) = 62.7, P < 0.001). CONCLUSION: cfDNA holds promise as a minimally invasive and clinically relevant prognostic biomarker in mCRC before initiating first-line oxaliplatin-based chemotherapy and may be a complex entity associated with tumor burden, liver metastases and systemic inflammatory response. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00145314.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers, Tumor/blood , Cell-Free Nucleic Acids/blood , Colorectal Neoplasms/blood , Colorectal Neoplasms/drug therapy , Liver Neoplasms/drug therapy , Liver Neoplasms/secondary , Biomarkers, Tumor/genetics , Cell-Free Nucleic Acids/genetics , Clinical Trials, Phase III as Topic , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Female , Fluorouracil/administration & dosage , Folic Acid/administration & dosage , Follow-Up Studies , Humans , Liver Neoplasms/blood , Liver Neoplasms/genetics , Lymphatic Metastasis , Male , Oxaliplatin/administration & dosage , Prognosis , Prospective Studies , Retrospective Studies , Survival RateABSTRACT
Just over 50% of patients with advanced rectal cancer have a poor response to chemoradiotherapy with resultant poor outcomes. Professor Glimelius reviews the evidence base for defining such patients and the potential role, if any, of further treatment.
Subject(s)
Chemoradiotherapy/methods , Neoadjuvant Therapy , Rectal Neoplasms/diagnostic imaging , Rectal Neoplasms/therapy , Chemoradiotherapy/mortality , Consensus , Disease-Free Survival , Female , Humans , Magnetic Resonance Imaging/methods , Male , Neoplasm Invasiveness/pathology , Neoplasm Recurrence, Local/mortality , Neoplasm Staging , Prognosis , Rectal Neoplasms/mortality , Rectal Neoplasms/pathology , Risk Assessment , Survival Analysis , Treatment FailureABSTRACT
BACKGROUND: Dihydropyrimidine dehydrogenase (DPD) tumour expression may provide added value to human equilibrative nucleoside transporter-1 (hENT1) tumour expression in predicting survival following pyrimidine-based adjuvant chemotherapy. METHODS: DPD and hENT1 immunohistochemistry and scoring was completed on tumour cores from 238 patients with pancreatic cancer in the ESPAC-3(v2) trial, randomised to either postoperative gemcitabine or 5-fluorouracil/folinic acid (5FU/FA). RESULTS: DPD tumour expression was associated with reduced overall survival (hazard ratio, HR = 1.73 [95% confidence interval, CI = 1.21-2.49], p = 0.003). This was significant in the 5FU/FA arm (HR = 2.07 [95% CI = 1.22-3.53], p = 0.007), but not in the gemcitabine arm (HR = 1.47 [0.91-3.37], p = 0.119). High hENT1 tumour expression was associated with increased survival in gemcitabine treated (HR = 0.56 [0.38-0.82], p = 0.003) but not in 5FU/FA treated patients (HR = 1.19 [0.80-1.78], p = 0.390). In patients with low hENT1 tumour expression, high DPD tumour expression was associated with a worse median [95% CI] survival in the 5FU/FA arm (9.7 [5.3-30.4] vs 29.2 [19.5-41.9] months, p = 0.002) but not in the gemcitabine arm (14.0 [9.1-15.7] vs. 18.0 [7.6-15.3] months, p = 1.000). The interaction of treatment arm and DPD expression was not significant (p = 0.303), but the interaction of treatment arm and hENT1 expression was (p = 0.009). CONCLUSION: DPD tumour expression was a negative prognostic biomarker. Together with tumour expression of hENT1, DPD tumour expression defined patient subgroups that might benefit from either postoperative 5FU/FA or gemcitabine.
Subject(s)
Carcinoma, Pancreatic Ductal/diagnosis , Dihydrouracil Dehydrogenase (NADP)/metabolism , Equilibrative Nucleoside Transporter 1/metabolism , Pancreatic Neoplasms/diagnosis , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers, Tumor/metabolism , Carcinoma, Pancreatic Ductal/drug therapy , Carcinoma, Pancreatic Ductal/metabolism , Carcinoma, Pancreatic Ductal/mortality , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Female , Fluorouracil/administration & dosage , Humans , Immunohistochemistry , Leucovorin/administration & dosage , Male , Middle Aged , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/metabolism , Pancreatic Neoplasms/mortality , Prognosis , Randomized Controlled Trials as Topic , Survival Analysis , Tissue Array Analysis , GemcitabineABSTRACT
BACKGROUND: The aim was to compare health-related quality-of-life (HRQOL) and cost-effectiveness between cytoreductive surgery with intraperitoneal chemotherapy (CRS + IPC) and systemic chemotherapy for patients with colorectal peritoneal metastases. METHODS: Patients included in the Swedish Peritoneal Trial comparing CRS + IPC and systemic chemotherapy completed the EORTC QLQ-C30 and SF-36 questionnaires at baseline, 2, 4, 6, 12, 18, and 24 months. HRQOL at 24 months was the primary endpoint. EORTC sum score, SF-36 physical and mental component scores at 24 months were calculated and compared for each arm and then referenced against general population values. Two quality-adjusted life-year (QALY) indices were applied (EORTC-8D and SF-6D) and an incremental cost-effectiveness ratio (ICER) per QALY gained was calculated. A projected life-time ICER per QALY gained was calculated using predicted survival according to Swedish population statistics. RESULTS: No statistical differences in HRQOL between the arms were noted at 24 months. Descriptively, survivors in the surgery arm had higher summary scores than the general population at 24 months, whereas survivors in the chemotherapy arm had lower scores. The projected life-time QALY benefit was 3.8 QALYs in favor of the surgery arm (p=0.06) with an ICER per QALY gained at 310,000 SEK (EORTC-8D) or 362,000 SEK (SF-6D) corresponding to 26,700-31,200 GBP. CONCLUSION: The HRQOL in patients with colorectal peritoneal metastases undergoing CRS + IPC appear similar to those receiving systemic chemotherapy. Two-year survivors in the CRS + IPC arm have comparable HRQOL to a general population reference. The treatment is cost-effective according to NICE guidelines.
Subject(s)
Antineoplastic Agents/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma/therapy , Colorectal Neoplasms/therapy , Cytoreduction Surgical Procedures/methods , Fluorouracil/administration & dosage , Hyperthermia, Induced/methods , Peritoneal Neoplasms/therapy , Quality of Life , Aged , Antineoplastic Agents/economics , Antineoplastic Combined Chemotherapy Protocols/economics , Carcinoma/physiopathology , Carcinoma/psychology , Carcinoma/secondary , Colorectal Neoplasms/pathology , Colorectal Neoplasms/physiopathology , Colorectal Neoplasms/psychology , Cost-Benefit Analysis , Cytoreduction Surgical Procedures/economics , Female , Fluorouracil/economics , Health Status , Humans , Hyperthermia, Induced/economics , Infusions, Parenteral , Male , Middle Aged , Organoplatinum Compounds/administration & dosage , Organoplatinum Compounds/economics , Oxaliplatin , Peritoneal Neoplasms/physiopathology , Peritoneal Neoplasms/psychology , Peritoneal Neoplasms/secondary , Quality-Adjusted Life YearsABSTRACT
BACKGROUND: Deoxycytidylate deaminase (DCTD) and ribonucleotide reductase subunit M1 (RRM1) are potential prognostic and predictive biomarkers for pyrimidine-based chemotherapy in pancreatic adenocarcinoma. METHODS: Immunohistochemical staining of DCTD and RRM1 was performed on tissue microarrays representing tumour samples from 303 patients in European Study Group for Pancreatic Cancer (ESPAC)-randomised adjuvant trials following pancreatic resection, 272 of whom had received gemcitabine or 5-fluorouracil with folinic acid in ESPAC-3(v2), and 31 patients from the combined ESPAC-3(v1) and ESPAC-1 post-operative pure observational groups. RESULTS: Neither log-rank testing on dichotomised strata or Cox proportional hazard regression showed any relationship of DCTD or RRM1 expression levels to survival overall or by treatment group. CONCLUSIONS: Expression of either DCTD or RRM1 was not prognostic or predictive in patients with pancreatic adenocarcinoma who had had post-operative chemotherapy with either gemcitabine or 5-fluorouracil with folinic acid.
Subject(s)
Adenocarcinoma/drug therapy , Biomarkers, Tumor/metabolism , DCMP Deaminase/metabolism , Pancreatic Neoplasms/drug therapy , Tumor Suppressor Proteins/metabolism , Adenocarcinoma/metabolism , Adenocarcinoma/mortality , Adenocarcinoma/surgery , Adult , Antineoplastic Combined Chemotherapy Protocols , Chemotherapy, Adjuvant , Disease-Free Survival , Humans , Immunohistochemistry , Pancreatectomy , Pancreatic Neoplasms/metabolism , Pancreatic Neoplasms/mortality , Pancreatic Neoplasms/surgery , Prognosis , Randomized Controlled Trials as Topic , Ribonucleoside Diphosphate Reductase , Tissue Array AnalysisABSTRACT
OBJECTIVE: This individual patient data (IPD) meta-analysis aimed to evaluate the effects of psychosocial interventions (PSI) on quality of life (QoL), emotional function (EF), and social function (SF) in patients with cancer, and to study moderator effects of demographic, clinical, personal, and intervention-related characteristics. METHODS: Relevant studies were identified via literature searches in 4 databases. We pooled IPD from 22 (n = 4217) of 61 eligible randomized controlled trials. Linear mixed-effect model analyses were used to study intervention effects on the post-intervention values of QoL, EF, and SF (z-scores), adjusting for baseline values, age, and cancer type. We studied moderator effects by testing interactions with the intervention for demographic, clinical, personal, and intervention-related characteristics, and conducted subsequent stratified analyses for significant moderator variables. RESULTS: PSI significantly improved QoL (ß = 0.14,95%CI = 0.06;0.21), EF (ß = 0.13,95%CI = 0.05;0.20), and SF (ß = 0.10,95%CI = 0.03;0.18). Significant differences in effects of different types of PSI were found, with largest effects of psychotherapy. The effects of coping skills training were moderated by age, treatment type, and targeted interventions. Effects of psychotherapy on EF may be moderated by cancer type, but these analyses were based on 2 randomized controlled trials with small sample sizes of some cancer types. CONCLUSIONS: PSI significantly improved QoL, EF, and SF, with small overall effects. However, the effects differed by several demographic, clinical, personal, and intervention-related characteristics. Our study highlights the beneficial effects of coping skills training in patients treated with chemotherapy, the importance of targeted interventions, and the need of developing interventions tailored to the specific needs of elderly patients.
Subject(s)
Emotional Adjustment , Neoplasms/psychology , Neoplasms/rehabilitation , Psychiatric Rehabilitation/psychology , Psychotherapy , Quality of Life/psychology , Social Adjustment , Adult , Aged , Female , Humans , Individuality , Male , Middle Aged , Psychiatric Rehabilitation/methods , Randomized Controlled Trials as TopicSubject(s)
Neoadjuvant Therapy , Rectal Neoplasms/drug therapy , Watchful Waiting , Humans , PrognosisABSTRACT
BACKGROUND: Microsatellite instability arises due to defect mismatch repair (MMR) and occurs in 10-20% of sporadic colorectal cancer. The purpose was to investigate correlations between defect MMR, prognosis and heredity for colorectal cancer in first-degree relatives. MATERIAL AND METHODS: Tumour tissues from 318 patients consecutively operated for colorectal cancer were analysed for immunohistochemical expression of MLH1, MSH2 and MSH6 on tissue microarrays. Information on KRAS and BRAF mutation status was available for selected cases. RESULTS: Forty-seven (15%) tumours displayed MSI. No correlation was seen between patients exhibiting MSI in the tumour and heredity (p = 0.789). Patients with proximal colon cancer and MSI had an improved cancer-specific survival (p = 0.006) and prolonged time to recurrence (p = 0.037). In a multivariate analysis including MSI status, gender, CEA, vascular and neural invasion, patients with MSS and proximal colon cancer had an impaired cancer-specific survival compared with patients with MSI (HR, 4.32; CI, 1.46-12.78). The same prognostic information was also seen in distal colon cancer; no recurrences seen in the eight patients with stages II and III distal colon cancer and MSI, but the difference was not statistically significant. CONCLUSION: No correlation between MSI and heredity for colorectal cancer in first-degree relatives was seen. Patients with MSI tumours had improved survival.
Subject(s)
Colorectal Neoplasms/genetics , DNA Mismatch Repair , Microsatellite Instability , Colorectal Neoplasms/pathology , Colorectal Neoplasms/surgery , DNA-Binding Proteins/genetics , Female , Humans , Immunohistochemistry , Male , MutL Protein Homolog 1/genetics , MutL Proteins/genetics , MutS Homolog 2 Protein/genetics , Mutation , Neoplasm Invasiveness , Neoplasm Proteins/genetics , Neoplasm Recurrence, Local , Neoplasm Staging , Prognosis , Proto-Oncogene Proteins B-raf/genetics , Proto-Oncogene Proteins p21(ras)/genetics , Risk Factors , Survival RateABSTRACT
BACKGROUND: Many patients with rectal cancer receive radiotherapy (RT) to reduce the risk of local recurrence. Radiation may give rise to adverse effects, including second primary cancers. In view of the divergent results of previous studies, the present study evaluated the risk of second primary cancer following RT in all randomized RT rectal cancer trials conducted in Sweden and in the Swedish ColoRectal Cancer Registry (SCRCR). METHODS: Patients included in five randomized trials and the SCRCR were linked to the Swedish Cancer Registry. Cox regression models estimated the hazard ratio (HR) of second primary cancer among patients who received RT compared with those who did not. RESULTS: A total of 13 457 patients were included in this study; 7024 (52·2 per cent) received RT and 6433 (47·8 per cent) had surgery alone. Overall, no increased risk of second primary cancer was observed with RT (HR 1·03; 95 per cent c.i. 0·92 to 1·15), independently of follow-up time and location within or outside of the irradiated volume. In the randomized trials, with longer follow-up (maximum 31 years), a slight increase was observed outside of (HR 1·33, 1·01 to 1·74) but not within (HR 1·11, 0·73 to 1·67) the irradiated volume. Irradiated men had a lower risk of prostate cancer than those treated with surgery alone (HR 0·68, 0·51 to 0·91). CONCLUSION: Overall, there was no increased risk of second primary cancer following RT for rectal cancer within or outside of the irradiated volume up to 20 years of follow-up. Men with rectal cancer who received RT had a reduced risk of prostate cancer.
Subject(s)
Adenocarcinoma/radiotherapy , Neoplasms, Radiation-Induced/etiology , Neoplasms, Second Primary/etiology , Rectal Neoplasms/radiotherapy , Adenocarcinoma/surgery , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasms, Radiation-Induced/diagnosis , Neoplasms, Radiation-Induced/epidemiology , Neoplasms, Second Primary/diagnosis , Neoplasms, Second Primary/epidemiology , Proportional Hazards Models , Radiotherapy, Adjuvant , Randomized Controlled Trials as Topic , Rectal Neoplasms/surgery , Registries , Risk Assessment , Risk Factors , SwedenABSTRACT
BACKGROUND: Preoperative radiotherapy (RT) for rectal cancer reduces local recurrence rates and possibly also mortality. Patient-related parameters such as age and comorbidity have a major impact on selection to preoperative RT. The aim of this study was to investigate how this selection influences the outcome in rectal cancer regardless of dose or fractionation of RT. METHODS: Data from the Swedish Colorectal Cancer Registry and the Swedish National Patient Register on all patients without distant metastasis who underwent elective trans-abdominal surgery for rectal cancer 2000-2010 in the Stockholm-Gotland region was retrieved. Factors influencing survival and recurrence were identified by Cox regression analyses. RESULTS: There were 2300 patients included. Among these 70.3% received preoperative RT. Three-year overall survival (OS), disease-free survival (DFS) and local recurrence rate were 80.2, 68.6 and 4.7%, respectively. All outcome measures were significantly improved over time. In a multivariable analysis in patients with comorbidity (Charlson comorbidity index score ≥1), OS were significantly better following preoperative RT than after surgery alone (HR 0.65, 95% CI 0.49-0.87). OS among patients with advanced age (≥80 years), was not influenced by preoperative RT. CONCLUSION: OS among patients with comorbidity was better following preoperative RT than after surgery alone while no differences were seen among the elderly. This indicates that the selection process may be optimised for the patients with advanced age but comorbidity should be used cautiously for exclusion of patients from preoperative RT.