Toxicity, response rates and survival outcomes of induction cisplatin and irinotecan followed by concurrent cisplatin, irinotecan and radiotherapy for locally advanced esophageal cancer.

OBJECTIVE: Cisplatin-based chemoradiotherapy is standard treatment for locally advanced esophageal and gastroesophageal cancers; however, the optimal chemotherapy regimen remains to be defined. METHODS: Retrospective single institution analysis of toxicities, response rates and survival outcomes in patients with cT3-4 or N1/M1a esophageal squamous cell or adenocarcinoma treated with induction cisplatin and irinotecan followed by concurrent cisplatin, irinotecan and radiotherapy. Secondary analysis for association of disease control and outcomes with demographic, tumor and treatment factors (including histology). RESULTS: Fifty-three patients were eligible for the present analysis. All patients underwent endoscopic ultrasonography and were either cT3-4 and/or cN1 disease. Fifty patients completed radiotherapy as planned (median dose 50.4 Gy, range 0-61.2), and 35 patients completed four cycles of chemotherapy as planned (range 1-4). Severe acute toxicities included Grade ≥ 3 neutropenia and esophagitis in 13 and 12 patients, respectively. There were no Grade 5 (fatal) toxicities noted. At mean survivor follow-up of 24.5 months (range 2.7-63), 17 patients were alive (8 without disease) and 36 deceased. Forty patients experienced disease recurrence, with initial loco-regional, distant or both failures in 28, 9 and 3 patients, respectively. Estimated 2-year overall survival and freedom from failure were 42 and 9%, respectively, without significant difference by histology. CONCLUSIONS: Cisplatin/irinotecan chemoradiotherapy is tolerable, demonstrating similar efficacy for squamous cell and adenocarcinoma esophageal cancers.

Acute complications of MammoSite brachytherapy: a single institution's initial clinical experience.

PURPOSE: To report the acute complications incurred by the initial 37 patients who underwent accelerated partial breast irradiation with the MammoSite balloon breast brachytherapy applicator at the Medical University of South Carolina. METHODS AND MATERIALS: Between May 2002 and March 2003, 37 patients with ductal carcinoma in situ or invasive carcinoma had MammoSite brachytherapy catheters successfully place after lumpectomy by one of four surgeons and were deemed eligible for high-dose-rate brachytherapy. An open technique was used in 32 implants and the scar entry technique was used in 5 implants. Patients had Stage pTis-pT2N1 with negative margins. A dose of 34 Gy was prescribed to 1 cm from the balloon surface using (192)Ir high-dose-rate brachytherapy and was delivered in 10 fractions twice daily. CT was used to confirm that the balloon surface was adherent to the lumpectomy cavity and to measure the balloon surface to skin surface distance. CT images and daily fluoroscopic simulations were used for treatment planning. Patients were assessed for acute toxicity on the day of therapy completion and 4 weeks after therapy by the radiation oncologist. In addition, all available data from radiation, surgical, and medical oncology were retrospectively reviewed for documentation of complications. All patients in this series had a minimal follow-up of 3 months; the mean follow-up for all patients was 7 months. RESULTS: The acute complications were categorized as operative wound complications, infections, skin toxicity, seromas, or catheter failures. Operative wound complications occurred in 3 patients (8%). Radiation Therapy Oncology Group Grade 2 and Grade 3 toxicity occurred in 2 (5.4%) and 1 (2.7%) patient, respectively. Six (16.2%) developed wound infections and 12 (32.4%) seromas. Catheter failures due to leak occurred in 2 patients (5.4%) and rupture in 3 (8%). CONCLUSION: The types of complications in this experience were similar to those in the Phase I trial of the MammoSite brachytherapy applicator. However, catheter failure due to leak occurred in our experience and was not described in the Phase I trial. The incidence of complications was greater in our series than in the Phase I trial; however, differences in toxicity scoring and the length of follow-up between the two series impeded direct comparisons. The incidences of complications over time reflect the steep learning curve for accelerated partial breast irradiation using the MammoSite brachytherapy applicator. Finally, radiation recall dermatitis developed in 1 patient treated after this review was completed.

Chest wall dose in MammoSite breast brachytherapy: radiobiologic estimations of late complication risk based on dose-volume considerations.

PURPOSE: To estimate the risk of late effects in women treated with MammoSite brachytherapy (MBT), the balloon catheters of which were placed near the ribs. METHODS AND MATERIALS: Upon reviewing 93 plans, 16 patients (17%) treated with MBT were considered to have received a high chest wall dose (>or=120% isodose line in contact with a rib). A dose-volume histogram was generated for this rib, and its distance from the MBT balloon measured. Using the linear quadratic equation, the equivalent dose, delivered in 10 fractions, to the dose that causes a 5% and 50% risk of rib late effects at 5 years using 2Gy per fraction, was calculated to be 37 and 44Gy, respectively. The rib volume receiving greater than or equal to these doses (V37 and V44) was correlated to the balloon-to-rib distance. Chest wall signs, symptoms, and radiologic findings for all 16 patients were recorded. RESULTS: The median balloon-to-rib distance was 4.8mm. The median values of V37 and V44 were 13.5% and 3.3%, respectively. All patients with a V37>or=15% and V44>or=5% had a minimum balloon-to-rib distance of <5mm. Two patients reported treatment-related chest wall tenderness (both had balloons placed <5mm from the chest wall), but neither presented with radiologic complications. CONCLUSIONS: Sixteen patients considered to receive relatively high chest wall doses had less than one-third of their primary rib volume being exposed to the estimated TD 5/5 and TD 50/5 doses. Therefore, we estimate the risk of late effects in women treated with MBT, the balloon catheters of which placed near the ribs were negligible, and believe that MBT remains a safe and effective treatment for selected patients with early stage breast cancer.

Outcomes in women treated with MammoSite brachytherapy or whole breast irradiation stratified by ASTRO Accelerated Partial Breast Irradiation Consensus Statement Groups.

PURPOSE: The American Society for Radiation Oncology published a Consensus Statement for accelerated partial breast irradiation identifying three groups: Suitable, Cautionary, and Unsuitable. The objective of this study was to compare oncologic outcomes in women treated with MammoSite brachytherapy (MB) vs. whole breast irradiation (WBI) after stratification into Statement groups. METHODS: Eligible women had invasive carcinoma or ductal carcinoma in situ (DCIS) ≤ 3 cm, and ≤ 3 lymph nodes positive. Women were stratified by radiation modality and Statement groups. Survival analysis methods including Kaplan-Meier estimation, Cox regression, and competing risks analysis were used to assess overall survival (OS), disease-free survival (DFS), time to local failure (TTLF), and tumor bed failure (TBF). RESULTS: A total of 459 (183 MB and 276 WBI) patients were treated from 2002 to 2009. After a median follow-up of 45 months, we found no statistical differences by stratification group or radiation modality with regard to OS and DFS. At 4 years TTLF or TBF were not statistically different between the cohorts. Univariate analysis in the MB cohort revealed that nodal positivity (pN1 vs. pN0) was related to TTLF (hazard ratio 6.39, p = 0.02). There was a suggestion that DCIS histology had an increased risk of failure when compared with invasive ductal carcinoma (hazard ratio 3.57, p = 0.06). CONCLUSIONS: MB and WBI patients stratified by Statement groups seem to combine women who will have similar outcomes regardless of radiation modality. Although outcomes were similar, we remain guarded in overinterpretation of these preliminary results until further analysis and long-term follow-up data become available. Caution should be used in treating women with DCIS or pN1 disease with MB.

Cisplatin/Irinotecan versus carboplatin/paclitaxel as definitive chemoradiotherapy for locoregionally advanced esophageal cancer.

OBJECTIVE: To compare toxicities, disease control, and survival outcomes for patients treated with either cisplatin/irinotecan versus carboplatin/paclitaxel concurrent chemoradiotherapy for locally advanced esophageal cancer. METHODS: Single-institution retrospective comparison between treatment groups: the cisplatin/irinotecan group was treated with 2 cycles of induction chemotherapy followed by concurrent chemoradiotherapy, whereas the carboplatin/paclitaxel group began with chemoradiotherapy followed by 2 additional cycles of chemotherapy. Acute toxicities, response rates, disease control, survival outcomes, and patterns of failure were compared between the groups. RESULTS: Between January 2000 and December 2007, 57 patients were identified for inclusion in the present study (38 cisplatin/irinotecan and 19 carboplatin/paclitaxel). Groups were well-balanced by clinical-, pathologic-, staging-, and treatment-related factors. Thirty-five patients (92%) in the cisplatin/irinotecan group and 18 patients (95%) in the carboplatin/paclitaxel group completed the concurrent phase of chemoradiotherapy. There were no significant differences in hematologic or nonhematologic toxicities between the groups. At a median survivor follow-up of 37.6 months (range: 7.3-59.3 months) for the entire population, 22 patients were alive (16 without evidence of disease). The 3-year overall survival estimates was 19.7% for the cisplatin/irinotecan group versus 56.1% for the carboplatin/paclitaxel group (P = 0.022). Estimated 3-year cancer-specific survivals were 24.6% for the cisplatin/irinotecan group versus 59.3% for the carboplatin/paclitaxel group (P = 0.033). CONCLUSION: Concurrent chemoradiotherapy with carboplatin/paclitaxel is well-tolerated and provided superior overall and disease-specific survival compared with cisplatin/irinotecan chemoradiotherapy in the present study population. Further investigation is warranted.

Once-daily radiotherapy to > or =59.4 Gy versus twice-daily radiotherapy to > or =45.0 Gy with concurrent chemotherapy for limited-stage small-cell lung cancer: a comparative analysis of toxicities and outcomes.

PURPOSE: The aim of this study was to compare toxicities, disease control, survival outcomes, and patterns of failure between groups of limited-stage small-cell lung cancer patients treated with once-daily versus twice-daily radiotherapy and concurrent chemotherapy. MATERIALS AND METHODS: This single-institution retrospective analysis included a comparison of two of radiotherapy regimens to planned doses of (1) > or =59.4 Gy at 1.8-2.0 Gy per once-daily fraction or (2) > or =45 Gy at 1.5 Gy per twice-daily fractions with concurrent platinum-based chemotherapy. Comparative analyses of toxicities and disease control were performed. RESULTS: A total of 71 patients were included in the present study (17 once-daily, 54 twice-daily). Patient, tumor, staging, and treatment factors were similar between the two treatment groups. Median planned radiotherapy doses were 60 Gy (range 59.4-70.0 Gy) and 45 Gy (range 45-51 Gy) for the once-daily and twice-daily groups, respectively. Acute toxicities were similar between the groups ( approximately 20% grade 3 esophagitis). At a median survival follow-up of 26.2 months (range 3.4-85.5 months), 42 patients had died. The 2-year overall survival estimates were similar at 43% and 49% for the once-daily versus twice-daily groups, respectively. Isolated in-field failures were similar between the two groups ( approximately 17%). CONCLUSION: The present analysis did not detect a statistically significant difference in acute toxicities, disease control, or survival outcomes in limited-stage small-cell lung cancer patients treated with concurrent chemotherapy and once-daily versus twice-daily radiotherapy.

Involved-field radiotherapy with concurrent chemotherapy for limited-stage small-cell lung cancer: disease control, patterns of failure and survival.

INTRODUCTION: Major randomised trials have employed elective nodal irradiation as part of combined modality therapy for limited-stage small-cell lung cancer (SCLC). The present investigation describes patterns of failure, disease control, and survival outcomes for involved-field radiotherapy with concurrent chemotherapy, without elective irradiation of uninvolved mediastinal nodal regions. METHODS: Retrospective analysis of SCLC patients treated with curative-intent accelerated, twice-daily radiotherapy and concurrent platinum-based chemotherapy at an academic institution. Treatment fields were reviewed, and patients who completed ≥42 Gy in 1.5 Gy twice-daily fractions to involved fields (without elective irradiation of uninvolved mediastinal lymphatic regions) were included in the present analysis. Initial patterns of failure, disease control and overall survival were recorded. RESULTS: Fifty-two patients fulfilled study criteria and were included in the present analysis. All but one patient completed three to four cycles of chemotherapy, and 10 patients experienced grade 3 acute esophagitis. At a median survivor follow-up of 35 months (range 5.5-91.9), 22 patients were alive (15 without recurrence) and 30 had died (23 of/with disease, four of unknown cause, two of other cause and one of treatment toxicity). Initial site(s) of disease failure were loco-regional only (11 patients), distant only (14) and loco-regional plus distant (3). There were no cases of isolated out-of-field mediastinal recurrence in the absence of supraclavicular or more distant disease. The estimated 3-year disease-free and overall survivals were 36% and 44%, respectively. CONCLUSIONS: Involved-field radiotherapy did not appear to have an adverse impact on the anticipated patterns of failure, disease control, or overall survival in this population of limited-stage SCLC patients.

Factors associated with severe acute esophagitis from hyperfractionated radiotherapy with concurrent chemotherapy for limited-stage small-cell lung cancer.

PURPOSE: To describe incidence and identify factors associated with development of severe acute esophagitis during hyperfractionated radiotherapy with concurrent chemotherapy (BID-CRT) in patients with limited-stage small-cell lung cancer (SCLC). METHODS AND MATERIALS: Retrospective cohort analysis of patient-, tumor-, and treatment-related variables was performed to identify factors associated with Radiation Therapy Oncology Group (RTOG) Grade 3 acute esophagitis. Twice-daily chemoradiotherapy (BID-CRT) involved 45 Gy at 1.5 Gy per fraction, treated twice daily with concurrent platinum-based chemotherapy. Logistic regression analyses were used to identify factors associated with esophagitis. RESULTS: Between June 1999 and June 2007, 48 patients underwent curative intent BID-CRT for SCLC and were included in the analysis. Median radiotherapy dose was 45 Gy (range, 42-51 Gy) delivered with a median 4 cycles of chemotherapy (range, 2-6). RTOG Grade 3 acute esophagitis developed in 11 patients. No patient developed Grade 4 or 5 esophagitis. Simple logistic regression analyses demonstrated a highly significant association between Grade 3 acute esophagitis and mean esophageal dose (p = 0.002) as well as relative volume dosimetric area under curve (RV-AUC; p = 0.004). Using multiple regression analysis, RV-AUC was identified as the only factor associated with Grade 3 esophagitis (p = 0.004). The most strongly associated dosimetric volume was the V15 (Grade 3 esophagitis rates of 15% vs. 64% for V15 <60% versus >or=60%, respectively). CONCLUSIONS: RV-AUC is the factor most associated with development of Grade 3 acute esophagitis in limited stage SCLC patients receiving BID-CRT.

Skin toxicity during breast irradiation: pathophysiology and management.

Radiotherapy is a critical component in the treatment of breast cancer, a disease that is estimated to have affected 203,500 US women in 2002. According to the data from some series, an estimated 90% of patients treated with radiotherapy for breast cancer will develop a degree of radiation-induced dermatitis. This review describes the indications and techniques of radiotherapy for breast cancer. The pathophysiology, clinical presentation, and contributing factors of radiation-related skin injury are discussed. A review of recent clinical research addressing skin toxicity is provided.

Referred otalgia in head and neck cancer: a unifying schema.

Pain referred to the ear is a commonly encountered clinical event, and the differential diagnoses that must be considered for pain in a normal ear are numerous. For physicians involved in the treatment of patients with referred ear pain, especially those involved in the care of patients with head and neck malignancies, a basic understanding of the mechanisms involved to produce this phenomenon is required. Several sources offer figures outlining the neuroanatomic basis of nonotogenic ear pain. On occasion, there has been omission of various components in this referred otalgia pathway, however. The authors propose a unified schema and outline potential areas of "nervous system error" giving rise to pain in a clinically normal ear.