Takuyo Kozuka

Late toxicity after definitive concurrent chemoradiotherapy for thoracic esophageal carcinoma.

PURPOSE To evaluate late cardiopulmonary toxicities after concurrent chemoradiotherapy (CCRT) for esophageal carcinomas. METHODS AND MATERIALS From February 2002 through April 2005, 74 patients with clinical Stage I-IVB carcinoma of the esophagus were treated with CCRT. Sixty-nine patients with thoracic squamous cell carcinoma were the core of this analysis. Patients received 60 Gy of radiation therapy in 30 fractions over 8 weeks, including a 2-week break, and received 2 cycles of fluorouracil/cisplatin chemotherapy concomitantly. Initial radiation fields included primary tumors, metastatic lymph nodes, and supraclavicular, mediastinal, and celiac nodes areas. Late toxicities were assessed with the late radiation morbidity scoring scheme of the Radiation Therapy Oncology Group/European Organiation for Research and Treatment of Cancer. RESULTS The median age was 67 years (range, 45-83 years). The median follow-up time was 26.1 months for all patients and 51.4 months for patients still alive at the time of analysis. Five cardiopulmonary toxic events of Grade 3 or greater were observed in 4 patients, Grade 5 heart failure and Grade 3 pericarditis in 1 patient, and Grade 3 myocardial infarction, Grade 3 radiation pneumonitis, and Grade 3 pleural effusion. The 2-year cumulative incidence of late cardiopulmonary toxicities of Grade 3 or greater for patients 75 years or older was 29% compared with 3% for younger patients (p = 0.005). CONCLUSION The CCRT used in this study with an extensive radiation field is acceptable for younger patients but is not tolerated by patients older than 75 years.

Phase II trial of S-1 and cisplatin with concurrent radiotherapy for locally advanced non-small-cell lung cancer

Background:To assess the efficacy and safety of S-1 and cisplatin with concurrent thoracic radiation for unresectable stage III non-small-cell lung cancer (NSCLC).Methods:Eligible patients were 20–74 years old and had histologically or cytologically confirmed NSCLC, a performance status of 0–1, and no prior chemotherapy. Patients were treated with cisplatin (60 mg m−2 on day 1) and S-1 (orally at 40 mg m−2 per dose, b.i.d., on days 1–14), with the treatment repeated every 4 weeks for four cycles. Beginning on day 2, a 60-Gy thoracic radiation dose was delivered in 30 fractions.Results:Of 50 patients, 48 were eligible. Partial response was observed in 42 patients (87.5%; 95% CI: 79.1–96.9%). This regimen was well tolerated. Common toxicities included grade 3/4 neutropenia (32%), grade 3/4 leukopenia (32%), grade 3/4 thrombocytopenia (4%), grade 3 febrile neutropenia (6%), grade 3 oesophagitis (10%), and grade 3 pneumonitis (5%). Median progression-free survival was 12.0 months and median overall survival was 33.1 months. The 1- and 2-year survival rates were 89.5 and 56%, respectively.Conclusion:This chemotherapy regimen with concomitant radiotherapy is a promising treatment for locally advanced NSCLC because of its high response rates, good survival rates, and mild toxicities.

Irinotecan plus cisplatin for therapy of small-cell carcinoma of the esophagus: report of 12 cases from single institution experience.

BACKGROUND Esophageal small-cell cancer is a rare disease, and standard therapy has not yet been established. METHODS A total of 12 esophageal small-cell carcinoma patients were treated with CPT-11 (70 mg/m(2)) on Days 1 and 15 and CPT-11 plus CDDP (80 mg/m(2)) on Day 1 with each cycle repeated every 4 weeks at our institution. RESULTS A total of 46 chemotherapy courses were given (median, 3.5). There were two complete responses and eight partial responses. The median survival time was 417 (97-1626) days, and three patients were still alive for >40 months. Grade 4 neutropenia was observed in two patients, Grade 4 anemia in one patient, Grade 3-4 diarrhea in three patients and Grade 3-4 hyponatremia in three patients. Other adverse reactions seen were mild with no treatment-related deaths observed. CONCLUSIONS To our knowledge, this is the first report of the series of more than 10 patients with small-cell carcinoma of the esophagus treated with the same chemotherapy regimen. The combination of CPT-11 and CDDP appears to be effective therapy of this disease with acceptable toxicity profile. We believe that this regimen is one of the options to be considered for treatment of esophageal small-cell carcinoma.

Treatment of thoracic esophageal carcinoma invading adjacent structures

T4 esophageal cancer is defined as the tumor invading adjacent structures, using tumor–node–metastasis (TNM) staging. For clinically T4 thoracic esophageal carcinoma, multimodality therapy, that is, neoadjuvant chemoradiotherapy (CRT) followed by surgery or definitive CRT, has generally been performed. However, the prognosis of patients with these tumors remains poor. Another strategy is needed to achieve curative treatment. In the present article, the treatment strategies employed to date are reviewed. Furthermore, the strategies for these malignancies are reassessed, based on our experiences. R1/2 and R0 resections are regarded as those with residual and no tumor after surgery. The present data show that patients who underwent R1/2 resection after neoadjuvant CRT experienced little survival benefit, while complete response (CR) cases after definitive CRT had comparatively better results. Therefore, curative surgery should not be attempted without down‐staging, and definitive CRT should be the initial treatment. Then surgery is indicated for the eradication of residual cancer cells. Close surveillance is essential for early detection of relapse even after CR, because the operation will gradually become increasingly difficult due to post‐CRT fibrosis. In conclusion, multimodality therapy consists of definitive CRT followed by R0 resection, which can be the treatment of choice for T4 esophageal carcinoma. These challenging treatments have the potential to constitute the most effective therapeutic strategy. (Cancer Sci 2007; 98: 937–942)

In Vivo Dosimetry of High-Dose-Rate Interstitial Brachytherapy in the Pelvic Region: Use of a Radiophotoluminescence Glass Dosimeter for Measurement of 1004 Points in 66 Patients With Pelvic Malignancy

PURPOSE To perform the largest in vivo dosimetry study for interstitial brachytherapy yet to be undertaken using a new radiophotoluminescence glass dosimeter (RPLGD) in patients with pelvic malignancy and to study the limits of contemporary planning software based on the results. PATIENTS AND METHODS Sixty-six patients with pelvic malignancy were treated with high-dose-rate interstitial brachytherapy, including prostate (n = 26), gynecological (n = 35), and miscellaneous (n = 5). Doses for a total of 1004 points were measured by RPLGDs and calculated with planning software in the following locations: rectum (n = 549), urethra (n = 415), vagina (n = 25), and perineum (n = 15). Compatibility (measured dose/calculated dose) was analyzed according to dosimeter location. RESULTS The compatibility for all dosimeters was 0.98 +/- 0.23, stratified by location: rectum, 0.99 +/- 0.20; urethra, 0.96 +/- 0.26; vagina, 0.91 +/- 0.08; and perineum, 1.25 +/- 0.32. CONCLUSIONS Deviations between measured and calculated doses for the rectum and urethra were greater than 20%, which is attributable to the independent movements of these organs and the applicators. Missing corrections for inhomogeneity are responsible for the 9% negative shift near the vaginal cylinder (specific gravity = 1.24), whereas neglect of transit dose contributes to the 25% positive shift in the perineal dose. Dose deviation of >20% for nontarget organs should be taken into account in the planning process. Further development of planning software and a real-time dosimetry system are necessary to use the current findings and to achieve adaptive dose delivery.

Preliminary Study of Correction of Original Metal Artifacts due to I-125 Seeds in Postimplant Dosimetry for Prostate Permanent Implant Brachytherapy

PurposeWe investigated a subtraction-based reprojection approach to reduce CT metal artifacts due to I-125 seeds and evaluated the clinical implications in postimplant dosimetry for prostate permanent implant brachytherapy.Materials and MethodsThe raw projection data were used to reduce metal artifacts due to I-125 seeds. CT images of the metal parts only were separated from the original CT images by setting the threshold for pixel value to that of the I-125 seeds. Using these images, sinograms of CT images with and without seeds were obtained by inverse Radon transform (iRT), and the sinogram of the metal image was subtracted from that of the original image. Finally, the image was reconstructed using the sinogram by Radon transform (RT). This technique was applied to a prostate phantom and to a patient undergoing prostate permanent implant brachytherapy.ResultsMetal artifacts from I-125 seeds were reduced in both the phantom and patient studies. This technique decreased the density of the inner region of seeds but enhanced the density of the seed edge, thereby facilitating the identification of seed number, orientation, and location.ConclusionThis method reduces metal artifacts from I-125 seeds, and has potential for decreasing the time required for and improving the accuracy of postimplant dosimetry.

Early onset recall pneumonitis during targeted therapy with sunitinib

BackgroundSunitinib interacts with radiation therapy, leading to synergism of the toxicities of these treatments. Radiation recall pneumonitis is a rare but serious complication of targeted therapy with tyrosine kinase inhibitors.Case presentationThe case of a patient with metastatic renal cell cancer (RCC) who developed recall pneumonitis on the first cycle of systemic sunitinib treatment is reported here. A 65-year-old man with RCC and bone metastasis underwent radiation therapy on his thoracic vertebrae (Th5-8) with a total dose of 24 Gy. Sunitinib (37.5 mg) was started 14 days after completing the radiation therapy. On the 14th day of sunitinib treatment, the patient developed progressive fever with worsening of dyspnea and general weakness. Treatment with pulse administration of prednisolone 1,000 mg for 3 days was initiated. Thereafter, the symptoms and the radiological findings regarding the interstitial filtration gradually improved over 7 days.ConclusionTo our knowledge, this is the first report of early onset recall pneumonitis during sunitinib therapy. At present, how sunitinib interacts with radiation therapy remains unclear. The possibility that tyrosine kinase inhibitor therapy, including with sunitinib, after radiation therapy may lead to adverse effects should be kept in mind.

Patterns of Practice in Intensity-modulated Radiation Therapy and Image-guided Radiation Therapy for Prostate Cancer in Japan

BACKGROUND The purpose of this study was to compare the prevalence of treatment techniques including intensity-modulated radiation therapy and image-guided radiation therapy in external-beam radiation therapy for prostate cancer in Japan. METHODS A national survey on the current status of external-beam radiation therapy for prostate cancer was performed in 2010. We sent questionnaires to 139 major radiotherapy facilities in Japan, of which 115 (82.7%) were returned. RESULTS Intensity-modulated radiation therapy was conducted at 67 facilities (58.3%), while image-guided radiation therapy was conducted at 70 facilities (60.9%). Simulations and treatments were performed in the supine position at most facilities. In two-thirds of the facilities, a filling bladder was requested. Approximately 80% of the facilities inserted a tube or encouraged defecation when the rectum was dilated. Some kind of fixation method was used at 102 facilities (88.7%). Magnetic resonance imaging was routinely performed for treatment planning at 32 facilities (27.8%). The median total dose was 76 Gy with intensity-modulated radiation therapy and 70 Gy with three-dimensional radiation therapy. The doses were prescribed at the isocenter at the facilities that conducted three-dimensional radiation therapy. In contrast, the dose prescription varied at the facilities that conducted intensity-modulated radiation therapy. Of the 70 facilities that could perform image-guided radiation therapy, 33 (47.1%) conducted bone matching, 28 (40.0%) conducted prostate matching and 9 (12.9%) used metal markers. Prostate or metal marker matching tended to produce a smaller margin than bone matching. CONCLUSIONS The results of the survey identified current patterns in the treatment planning and delivery processes of external-beam radiation therapy for prostate cancer in Japan.

Dose-Escalation Study of Three-Dimensional Conformal Thoracic Radiotherapy With Concurrent S-1 and Cisplatin for Inoperable Stage III Non-Small-Cell Lung Cancer

PURPOSE To determine the recommended dose (RD) in concurrent conformal radiotherapy with S-1 and cisplatin chemotherapy for inoperable stage III non-small-cell lung cancer. PATIENTS AND METHODS Eligible patients with inoperable stage III non-small-cell lung cancer, age ≥ 20 years, performance status 0-1 received 4 cycles of intravenous cisplatin (60 mg/m(2), day 1) and oral S-1 (80, 100, or 120 mg based on body surface area, days 1-14) repeated every 4 weeks. Radiation doses were 66, 70, and 74 Gy for arms 1, 2, and 3, respectively. RESULTS A total of 24 patients were enrolled in our study, including 6 in arm 1, 6 in arm 2, and 12 in arm 3. The patients consisted of 14 men and 10 women, with a median age of 63 years (range, 44-73 years). The median follow-up was 27.3 months (range, 8.5-42.6 months) for all patients and 33.9 months (range, 15.2-42.6 months) for those still alive. Grade 3 febrile neutropenia, lung toxicities, and heart toxicities occurred in 2, 2, and 2 patients, respectively. Dose-limiting toxicity occurred in 2, none, and 1 patient in arms 1, 2, and 3, respectively. The median survival was not reached, and the 2-year survival rate was 70% (95% CI, 51%-89%). Two-year local relapse-free survival and distant metastasis-free survival were 74% (95% CI, 56%-92%) and 45% (95% CI, 25%-65%), respectively. CONCLUSIONS High-dose radiotherapy with S-1 and cisplatin is feasible, and 74 Gy was determined as the recommended dose.

High-dose-rate interstitial brachytherapy for gynecologic malignancies—dosimetric changes during treatment period

To overcome cranio-caudal needle displacement in pelvic high-dose-rate interstitial brachytherapy (HDRIB), we have been utilizing a fullystretched elastic tape to thrust the template into the perineum. The purpose of the current study was to evaluate dosimetric changes during the treatment period using this thrusting method, and to explore reproducible planning methods based on the results of the dosimetric changes. Twenty-nine patients with gynecologic malignancies were treated with HDRIB at the Cancer Institute Hospital. Pre-treatment and post-treatment computed tomography (CT) scans were acquired and a virtual plan for post-treatment CT was produced by applying the dwell positions/times of the original plan. For the post-treatment plan, D90 for the clinical target volume (CTV) and D2cc for the rectum and bladder were assessed and compared with that for the original plan. Cranio-caudal needle displacement relative to CTV during treatment period was only 0.7 ± 1.9 mm. The mean D90 values for the CTV in the pre- and post-treatment plans were stable (6.8 Gy vs. 6.8 Gy) and the post-treatment/pre-treatment D90 ratio was 1.00 ± 0.08. The post-/pre-treatment D2cc ratio was 1.14 ± 0.22 and the mean D2cc for the rectum increased for the post-treatment plan (5.4 Gy vs. 6.1 Gy), especially when parametrial infiltration was present. The mean D2cc for the bladder was stable (6.3 Gy vs. 6.6 Gy) and the ratio was 1.06 ± 0.20. Our thrusting method achieved a stable D90 for the CTV, in contrast to previous prostate HDRIB reports displaying reductions of 35–40% for D90 during the treatment period.