Reduction of radiation pneumonitis by V20-constraints in breast cancer

<p>Abstract</p> <p>Introduction</p> <p>Adjuvant local-regional radiotherapy (LRRT) is routinely recommended for breast cancer patients. It is well known being related to pulmonary side-effects. We studied post-RT radiological changes on X-ray and CT, and correlated the findings with Quality of Life (QoL), common dosimetric factors and co-variates. The results were compared with a previously reported cohort of 137 irradiated women.</p> <p>Methods</p> <p>88 women underwent chest X-ray and CT pre-and 4-5 months after 3-D planned LRRT, minimizing the dose to the ipsilateral lung to V₂₀< 30%. The lung field was divided into 3 regions and the development of post-RT density changes were graded (0-3). Patients with radiological changes were compared with non-responders. Clinical symptoms were registered and data on patient and treatment related co-variates were gathered prospectively. The ipsilateral lung dosimetric factors V₁₃, V₂₀, V₃₀and mean dose were calculated and QoL was assessed before and 4 months after RT.</p> <p>Results</p> <p>The use of dose-volume constraints significally reduced moderate-severe radiological changes on chest X-ray compared with our earlier study (Chi square trend test: p < 0.001). Symptomatic pneumonitis was also rare in the present study. No agreement was found between CT and chest X-ray as diagnostic tools for post-RT pneumonitis. V₁₃correlated independently with radiological changes on CT (logistic regression: p = 0.04; ROC area: 0.7). The Co-variates smoking habits, age, chemotherapy, endocrine or trastuzumab therapy did not influence the outcome on multivariate analysis. QoL changes in physical function, i.e. fatigue, dyspnoea were not detected but there was a trend for a worse recovery after chemotherapy in patients with high V₁₃(Spearman Rank Correlation: p < 0.05).</p> <p>Conclusions</p> <p>The use of dose-volume constraints significantly reduced post-RT radiological changes on chest X-ray in LRRT for BC. The lung changes on CT were also generally limited when we used this strategy and was not always picked up on chest X-ray. Variation in V₁₃alone was correlated with occurrence of lung changes on CT.</p

Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): a multicentre, open-label, randomised, phase 3 trial

BACKGROUND: The ESPAC-3 trial showed that adjuvant gemcitabine is the standard of care based on similar survival to and less toxicity than adjuvant 5-fluorouracil/folinic acid in patients with resected pancreatic cancer. Other clinical trials have shown better survival and tumour response with gemcitabine and capecitabine than with gemcitabine alone in advanced or metastatic pancreatic cancer. We aimed to determine the efficacy and safety of gemcitabine and capecitabine compared with gemcitabine monotherapy for resected pancreatic cancer. METHODS: We did a phase 3, two-group, open-label, multicentre, randomised clinical trial at 92 hospitals in England, Scotland, Wales, Germany, France, and Sweden. Eligible patients were aged 18 years or older and had undergone complete macroscopic resection for ductal adenocarcinoma of the pancreas (R0 or R1 resection). We randomly assigned patients (1:1) within 12 weeks of surgery to receive six cycles of either 1000 mg/m(2) gemcitabine alone administered once a week for three of every 4 weeks (one cycle) or with 1660 mg/m(2) oral capecitabine administered for 21 days followed by 7 days' rest (one cycle). Randomisation was based on a minimisation routine, and country was used as a stratification factor. The primary endpoint was overall survival, measured as the time from randomisation until death from any cause, and assessed in the intention-to-treat population. Toxicity was analysed in all patients who received trial treatment. This trial was registered with the EudraCT, number 2007-004299-38, and ISRCTN, number ISRCTN96397434. FINDINGS: Of 732 patients enrolled, 730 were included in the final analysis. Of these, 366 were randomly assigned to receive gemcitabine and 364 to gemcitabine plus capecitabine. The Independent Data and Safety Monitoring Committee requested reporting of the results after there were 458 (95%) of a target of 480 deaths. The median overall survival for patients in the gemcitabine plus capecitabine group was 28·0 months (95% CI 23·5-31·5) compared with 25·5 months (22·7-27·9) in the gemcitabine group (hazard ratio 0·82 [95% CI 0·68-0·98], p=0·032). 608 grade 3-4 adverse events were reported by 226 of 359 patients in the gemcitabine plus capecitabine group compared with 481 grade 3-4 adverse events in 196 of 366 patients in the gemcitabine group. INTERPRETATION: The adjuvant combination of gemcitabine and capecitabine should be the new standard of care following resection for pancreatic ductal adenocarcinoma

Patients' preferences for subcutaneous trastuzumab versus conventional intravenous infusion for the adjuvant treatment of HER2-positive early breast cancer: final analysis of 488 patients in the international, randomized, two-cohort PrefHer study

PrefHer revealed compelling and consistent patient preference for subcutaneous (s.c.) trastuzumab, regardless of delivery by single-use injection device or hand-held syringe. s.c. trastuzumab was well-tolerated and safety data, including immunogenicity, were consistent with previous reports. No new safety signals were identified compared with the known intravenous trastuzumab profile in early breast cance

Neo-adjuvant chemotherapy followed by surgery and chemotherapy or by surgery and chemoradiotherapy for patients with resectable gastric cancer (CRITICS)

<p>Abstract</p> <p>Background</p> <p>Radical surgery is the cornerstone in the treatment of resectable gastric cancer. The Intergroup 0116 and MAGIC trials have shown benefit of postoperative chemoradiation and perioperative chemotherapy, respectively. Since these trials cannot be compared directly, both regimens are evaluated prospectively in the CRITICS trial. This study aims to obtain an improved overall survival for patients treated with preoperative chemotherapy and surgery by incorporating radiotherapy concurrently with chemotherapy postoperatively.</p> <p>Methods/design</p> <p>In this phase III multicentre study, patients with resectable gastric cancer are treated with three cycles of preoperative ECC (epirubicin, cisplatin and capecitabine), followed by surgery with adequate lymph node dissection, and then either another three cycles of ECC or concurrent chemoradiation (45 Gy, cisplatin and capecitabine). Surgical, pathological, and radiotherapeutic quality control is performed. The primary endpoint is overall survival, secondary endpoints are disease-free survival (DFS), toxicity, health-related quality of life (HRQL), prediction of response, and recurrence risk assessed by genomic and expression profiling. Accrual for the CRITICS trial is from the Netherlands, Sweden, and Denmark, and more countries are invited to participate.</p> <p>Conclusion</p> <p>Results of this study will demonstrate whether the combination of preoperative chemotherapy and postoperative chemoradiotherapy will improve the clinical outcome of the current European standard of perioperative chemotherapy, and will therefore play a key role in the future management of patients with resectable gastric cancer.</p> <p>Trial registration</p> <p>clinicaltrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT00407186">NCT00407186</a></p

Short-term pulmonary side-effects following radiation therapy in breast cancer

The purpose of this dissertation was to study the short-term pulmonary sideeffects following adjuvant radiotherapy for breast cancer in terms of clinical pulmonary complications, loss of pulmonary function and radiological abnormalities, and the association to irradiated lung volume and dose. Furthermore, we wanted to estimate the influence of covariates, e.g. age, sequential chemotherapy, concurrent tamoxifen treatment, smoking habits, pretreatment functional level and premorbidity, on the early radiation-induced response of lung. Severe pulmonary complications, i.e. managed with corticosteroids, were diagnosed among 10 % of the patients who were treated with loco-regional radiotherapy including the internal mammary nodes (IMN). Age and reduced pre-treatment functional level were independently associated with pulmonary complications. The mean irradiated ipsilateral lung volume receiving more than 20 Gy was larger among the patients diagnosed with both clinical and radiological pneumonitis than in patients experiencing neither of the two side-effects. Severe pulmonary complications were very rare (<1%) among patients who were treated with local radiotherapy. A mean reduction in pulmonary function, i.e. vital capacity, was observed among patients treated with loco-regional radiotherapy including the IMN compared both to patients in whom the IMN were excluded from the target volume and to patients who were treated with local radiotherapy. The mean reduction in vital capacity among patients who were diagnosed with severe pulmonary complications was clinically significant and equivalent to the loss of 3/4 of a lung lobe. Furthermore, postirradiatory reduction in vital capacity was independently associated to only irradiated lung volume. The patients who were pre-treated with chemotherapy had lower mean diffusion capacity than expected, i.e. 78 % of predicted, at baseline and this was probably caused by drug-induced toxicity. Radiological abnormalities were most often seen among patients in whom large lung volumes had been included within the fields of irradiation. Postirradiatory radiological abnormalities were more frequently seen in older patients and were associated with both pulmonary complications and loss of vital capacity. Computerised tomography was found to be a more sensitive technique for diagnosing postirradiatory radiological abnormalities and was more strongly associated to functional end-points than chest radiography. In conclusion, loco-regional radiotherapy in breast cancer is associated with clinically significant short-term pulmonary side-effects. The results of this work also suggest that a more individualised treatment planning aimed at reducing the irradiated lung volume receiving more than 20 Gy may reduce the incidence of pulmonary side-effects in this group of patients

Estimated Risk of Radiation-Induced Cancer after Thymoma Treatments with Proton- or X-ray Beams

We compared the calculated risks of radiation-induced secondary malignant neoplasms (SMNs) for patients treated for thymic tumors with 3D-CRT, IMRT, or single-field uniform dose (SFUD) proton beam therapy (PBT) using the pencil beam scanning (PBS) technique. A cancer-induction model based on the organ equivalent dose (OED) concept was used. For twelve patients, treated with 3D-CRT for thymic tumors, alternative IMRT and SFUD plans were retrospectively prepared. The resulting DVHs for organs at risk (OARs) were extracted and used to estimate the risk of SMNs. The OED was calculated using a mechanistic model for carcinoma induction. Two limit cases were considered; the linear-exponential model, in which the repopulation/repair of the cells is neglected, and the plateau model, in which full repopulation/repair of the irradiated cells is assumed. The calculated risks for SMNs for the different radiation modalities and dose-relation models were used to calculate relative risks, which were compared pairwise. The risks for developing SMNs were reduced for all OARs, and for both dose-relation models, if SFUD was used, compared to 3D-CRT and IMRT. In conclusion, PBS shows a potential benefit to reduce the risk of SMNs compared to 3D-CRT and IMRT in the treatment of thymic tumors

Multicentre phase I-II trial of capecitabine and oxaliplatin in combination with radiotherapy for unresectable pancreatic and biliary tract cancer: The CORGI-U study

Background and Purpose: In this multicentre phase I-II trial we evaluated the feasibility and efficacy of capecitabine and oxaliplatin followed by the combination of these two drugs with radiotherapy in patients with locally advanced pancreatic or biliary tract cancer. Material and methods: Thirty-nine patients with inextirpable adenocarcinoma of the pancreas, gallbladder or extrahepatic bile ducts were included. Two cycles of XELOX (capecitabine 1000 mg/m(2) bid d1-14 + oxaliplatin 130 mg/m(2) d1, q3w) were followed by XELOX-RT (radiotherapy (50.4 Gy), combined with capecitabine 750-675 mg/m(2) bid every radiotherapy day and oxaliplatin 40-30 mg/m(2) once weekly). Primary end-points were tolerance (phase I) and objective response (phase II). Results: The maximum tolerated doses of oxaliplatin and capecitabine to combine with irradiation were 30 mg/m(2) and 675 mg/m(2), respectively. Twenty-one percent (95% CI: 9-38%) of evaluable patients achieved partial response. Five patients went through surgery (three R0 resections). Two-year survival was 28%, and estimated local tumour control rate at 2 years was 72%. The most common grade 3-4 toxicity was nausea and vomiting. Conclusions: XELOX-RT (30 mg/m(2) oxaliplatin/675 mg/m(2) capecitabine in combination with 50.4 Gy/28 fractions) was well tolerated and effective for locally advanced pancreatic and biliary tract cancer. (C) 2010 Published by Elsevier Ireland Ltd. Radiotherapy and Oncology 95 (2010) 292-29

Circulating tumor DNA (ctDNA) in adjuvant therapy of early stage colon cancer: current status and future perspectives

International audienceBackgroundThis article reviews the current knowledge on circulating tumor DNA (ctDNA) in early stage colon cancer and ongoing trials on ctDNA-guided treatment in the adjuvant setting.MethodsA literature search of Pubmed was performed to identify studies on ctDNA in early stage colon cancer and neoadjuvant or adjuvant treatment. For ongoing trials, we searched clinicaltrials.gov and the Australian New Zealand Clinical Trials Registry (ANZCTR).ResultsSeveral studies show that ctDNA is a strong predictor for recurrence and survival after surgery and adjuvant chemotherapy. The specificity of this marker is extremely high, and the sensitivity is increasing with the development of technology. Recurrences can be detected very early and the analysis can potentially be used to guide neoadjuvant and adjuvant treatment. Ongoing and planned studies are now looking into escalation and de-escalation of therapy according to ctDNA-status after surgery.ConclusionSerial measurement of ctDNA shows great promise as a marker for both prognosis and response to treatment in early colon cancer. Future studies will show whether we can use this analysis for tailoring treatment for patients in the adjuvant and neoadjuvant setting. With improved technology, ctDNA has the potential of becoming a ‘game-changer’ in the treatment of early stage colon cancers