Is Extended Volume of External Beam Irradiation Beneficial in Post-esophagectomy High Risk Patients Receiving Combined Chemoradiation Therapy?

OBJECTIVE: To assess the value of extended volume irradiation with anastomotic coverage in high risk resected esophageal cancer patients. METHOD: A retrospective study was undertaken at LRCC from 1989-1999 for high risk resected esophageal cancer patients. Adjuvant treatments consisted of 4 cycles of chemotherapy (epirubicin/fluorouracil/cisplatin or cisplatin/fluorouracil), and local regional irradiation with or without coverage of the anastomotic site. Radiation dose ranged from 45-60Gy at 1.8-2.0 Gy/fraction given with initial anterior-posterior/posterior-anterior arrangement with either extended (with anastomotic coverage) or small (without anastomotic coverage) field followed by oblique fields for boost. RESULT: One hundred eighty-eight charts were reviewed. Seventy-two patients were eligible for post-resection chemoradiation therapy. Three patients had disease progression prior to therapy, and 69 patients were analyzed. There were 81% T3N1 and 13% T2N1. Thirty-four patients had margin involvements (radial 53%; proximal/distal 32%), 65% were adenocarcinoma and 33% were squamous carcinoma. Median followup was 23.6 months (3.4 - 78.4 months). Two year survival was 50%; 5yr 24%. Relapse rate was 62.3% and median time to relapse was 20 months. Recurrence locally to anastomosis or adjacent to anastomosis was 9/43(20.9%) with small field and 2/26(7.7%) with extended field. Of 31 patients with relapse outside anastomosis, 14/20(70%) relapsed locoregional/distal when treated with small field and 3/11(27%) relapsed locoregional/distal when treated with extended field (p=0.02). There was no excess treatment interruption or chronic gastrointestinal toxicity with extended field irradiation. CONCLUSION: There is significant decrease in locoregional/distal relapse with use of extended field in high risk resected esophageal cancer patients

Concurrent chemoradiation with capecitabine and weekly irinotecan as preoperative treatment for rectal cancer: results from a phase I/II study

The aim of this study was to investigate the efficacy and safety of chemoradiation using capecitabine and irinotecan as neoadjuvant therapy for patients with rectal cancer. Conventional radiation was given at daily fractions of 1.8 Gy on 5 days a week for a total dose of 55.8 (50.4+5.4) Gy. Concurrently, irinotecan 40 mg m−2 once weekly and capecitabine continuously at dose levels of 500, 650, 750 and 825 mg m−2 twice daily were administered. Surgery was performed 4–6 weeks following completion of chemoradiation. A total of 28 patients (3 UICC II, 25 UICC III) were enrolled and all received treatment. Dose-limiting toxicity was diarrhoea grade IV and hand–foot syndrome at the 825 mg m−2 dose level. The maximum tolerated dose of capecitabine was 750 mg m−2. Diarrhoea was the most common toxicity: grade III in nine patients. Two patients died, one due to pneumonia and one due to sudden cardiac death. A complete response and only microfocal residual tumour disease was achieved in four and three patients (27%). In all, 25 of 28 patients undergoing surgery, 24 (96%) had R0 resection. Preoperative chemoradiation based on continuous daily capecitabine and weekly irinotecan appears to tolerated and effective in patients with rectal cancer

Intensified concurrent chemoradiotherapy with 5-fluorouracil and irinotecan as neoadjuvant treatment in patients with locally advanced rectal cancer

This study aimed to evaluate the feasibility and efficacy of neoadjuvant chemoradiotherapy intensified with irinotecan in patients with locally advanced rectal cancer. Eligible patients had nonmetastatic disease at a locally advanced stage that made R0 resection and sphincter preservation uncertain. They received preoperative radiation over 6 weeks to 45 Gy and boost of 5.4 Gy and concurrent continuous infusion 5-fluorouracil 250 mg m−2 day−1 and weekly irinotecan 40 mg m−2. In all, 37 patients entered the study. T stage at baseline as determined by ultrasound was T2/T3/T4 in 2/19/16 patients; 31 patients had lymph node involvement. The predominant toxicity was diarrhoea (grade 3/4 in 10/2 patients). Haematologic toxicity and surgical complications were moderate. Among 36 patients undergoing surgery, 32 (89%) had R0 resection and 23 (64%) sphincter preservation. Pathologic complete response (pCR) was achieved in eight (22%) of 36 patients, and 10 patients (28%) had only microscopic residual disease. At 4 years, overall survival was 66%, disease-free survival 73%, local relapse rate 7%, and distant failure rate 24%. Extent of resection and postoperative nodal status were significant predictors of overall and disease-free survival. Intensified neoadjuvant chemoradiotherapy with irinotecan can be safely administered and results in a high pCR rate

Irinotecan+5-fluorouracil with concomitant pre-operative radiotherapy in locally advanced non-resectable rectal cancer: a phase I/II study

In the UK, 10% of patients diagnosed with rectal cancer have inoperable disease at presentation. This study ascertained whether the resectability rate of inoperable locally advanced rectal cancer was improved by administration of intravenous irinotecan, 5-fluorouracil (5-FU) and pelvic radiotherapy. During phase I of the trial (n=12), the dose of irinotecan was escalated in three-patient cohorts from 50 mg m−2 to 60 mg m−2 to 70 mg m−2 to identify the maximum tolerated dose (60 mg m−2). In phase II, 31 patients with non-resectable disease received 45 Gy radiotherapy and 5-FU infusions (200 mg m−2 per day) for 5 weeks. Irinotecan (60 mg m−2) was given on days 1, 8, 15 and 22. After treatment, patients were operated on if possible. Thirty patients completed the protocol, 28 underwent surgery. Before surgery, MRI restaging of 24 patients showed that 19 (79%) had a reduction in tumour stage after treatment (seven complete clinical response and 12 partial). Of 27 patients followed up after surgery, 22 (81%) had clear circumferential resection margins. Disease-free and overall survival estimates at 3 years were 65 and 90%, respectively. The regimen was well tolerated. Irinotecan, 5-FU and radiotherapy results in tumour downgrading, allowing resection of previously inoperable tumour with acceptable toxicity

Radiofrequency ablation of lung tumours

Pulmonary radiofrequency ablation (RFA) has become an increasingly adopted treatment option for primary and metastatic lung tumours. It is mainly performed in patients with unresectable or medically inoperable lung neoplasms. The immediate technical success rate is over 95%, with a low periprocedural mortality rate and 8–12% major complication rate. Pneumothorax represents the most frequent complication, but requires a chest tube drain in less than 10% of cases. Sustained complete tumour response has been reported in 85–90% of target lesions. Lesion size represents the most important risk factor for local recurrence. Survival data are still scarce, but initial results are very promising. In patients with stage I non-small-cell lung cancer, 1- and 2-year survival rates are within the ranges of 78–95% and 57–84%, respectively, with corresponding cancer-specific survival rates of 92% and 73%. In selected cases, the combination of RFA and radiotherapy could improve these results. In patients with colorectal lung metastasis, initial studies have reported survival data that compare favourably with the results of metastasectomy, with up to a 45% 5-year survival rate. Further studies are needed to understand the potential role of RFA as a palliative treatment in more advanced disease and the possible combination of RFA with other treatment options

Prognostic indices for brain metastases – usefulness and challenges

<p>Abstract</p> <p>Background</p> <p>This review addresses the strengths and weaknesses of 6 different prognostic indices, published since the Radiation Therapy Oncology Group (RTOG) developed and validated the widely used 3-tiered prognostic index known as recursive partitioning analysis (RPA) classes, i.e. between 1997 and 2008. In addition, other analyses of prognostic factors in groups of patients, which typically are underrepresented in large trials or databases, published in the same time period are reviewed.</p> <p>Methods</p> <p>Based on a systematic literature search, studies with more than 20 patients were included. The methods and results of prognostic factor analyses were extracted and compared. The authors discuss why current data suggest a need for a more refined index than RPA.</p> <p>Results</p> <p>So far, none of the indices has been derived from analyses of all potential prognostic factors. The 3 most recently published indices, including the RTOG's graded prognostic assessment (GPA), all expanded from the primary 3-tiered RPA system to a 4-tiered system. The authors' own data confirm the results of the RTOG GPA analysis and support further evaluation of this tool.</p> <p>Conclusion</p> <p>This review provides a basis for further refinement of the current prognostic indices by identifying open questions regarding, e.g., performance of the ideal index, evaluation of new candidate parameters, and separate analyses for different cancer types. Unusual primary tumors and their potential differences in biology or unique treatment approaches are not well represented in large pooled analyses.</p

Iodine-125 brachytherapy for brain tumours - a review

Iodine-125 brachytherapy has been applied to brain tumours since 1979. Even though the physical and biological characteristics make these implants particularly attractive for minimal invasive treatment, the place for stereotactic brachytherapy is still poorly defined

Association of Radiotherapy Duration With Clinical Outcomes in Patients With Esophageal Cancer Treated in NRG Oncology Trials: A Secondary Analysis of NRG Oncology Randomized Clinical Trials

IMPORTANCE: For many types of epithelial malignant neoplasms that are treated with definitive radiotherapy (RT), treatment prolongation and interruptions have an adverse effect on outcomes. OBJECTIVE: To analyze the association between RT duration and outcomes in patients with esophageal cancer who were treated with definitive chemoradiotherapy (CRT). DESIGN, SETTING, AND PARTICIPANTS: This study was an unplanned, post hoc secondary analysis of 3 prospective, multi-institutional phase 3 randomized clinical trials (Radiation Therapy Oncology Group [RTOG] 8501, RTOG 9405, and RTOG 0436) of the National Cancer Institute-sponsored NRG Oncology (formerly the National Surgical Adjuvant Breast and Bowel Project, RTOG, and Gynecologic Oncology Group). Enrolled patients with nonmetastatic esophageal cancer underwent definitive CRT in the trials between 1986 and 2013, with follow-up occurring through 2014. Data analyses were conducted between March 2022 to February 2023. EXPOSURES: Treatment groups in the trials used standard-dose RT (50 Gy) and concurrent chemotherapy. MAIN OUTCOMES AND MEASURES: The outcomes were local-regional failure (LRF), distant failure, disease-free survival (DFS), and overall survival (OS). Multivariable models were used to examine the associations between these outcomes and both RT duration and interruptions. Radiotherapy duration was analyzed as a dichotomized variable using an X-Tile software to choose a cut point and its median value as a cut point, as well as a continuous variable. RESULTS: The analysis included 509 patients (median [IQR] age, 64 [57-70] years; 418 males [82%]; and 376 White individuals [74%]). The median (IQR) follow-up was 4.01 (2.93-4.92) years for surviving patients. The median cut point of RT duration was 39 days or less in 271 patients (53%) vs more than 39 days in 238 patients (47%), and the X-Tile software cut point was 45 days or less in 446 patients (88%) vs more than 45 days in 63 patients (12%). Radiotherapy interruptions occurred in 207 patients (41%). Female (vs male) sex and other (vs White) race and ethnicity were associated with longer RT duration and RT interruptions. In the multivariable models, RT duration longer than 45 days was associated with inferior DFS (hazard ratio [HR], 1.34; 95% CI, 1.01-1.77; P = .04). The HR for OS was 1.33, but the results were not statistically significant (95% CI, 0.99-1.77; P = .05). Radiotherapy duration longer than 39 days (vs ≤39 days) was associated with a higher risk of LRF (HR, 1.32; 95% CI, 1.06-1.65; P = .01). As a continuous variable, RT duration (per 1 week increase) was associated with DFS failure (HR, 1.14; 95% CI, 1.01-1.28; P = .03). The HR for LRF 1.13, but the result was not statistically significant (95% CI, 0.99-1.28; P = .07). CONCLUSIONS AND RELEVANCE: Results of this study indicated that in patients with esophageal cancer receiving definitive CRT, prolonged RT duration was associated with inferior outcomes; female patients and those with other (vs White) race and ethnicity were more likely to have longer RT duration and experience RT interruptions. Radiotherapy interruptions should be minimized to optimize outcomes