Neoadjuvant Modified Short-course Radiotherapy for Stage IV Rectal Cancer.

BACKGROUND/AIM: This study aimed to assess the clinical outcomes of neoadjuvant modified short-course radiotherapy (mSC-RT) for rectal metastatic adenocarcinoma. PATIENTS AND METHODS: Data from 14 patients who underwent mSC-RT followed by surgery for primary tumors were retrospectively analyzed. Twelve patients received systemic chemotherapy for 18 weeks. A 2.5 Gy dose twice daily, up to a total dose of 25 Gy in 10 fractions, over 5 consecutive days was administered through mSC-RT. Surgery for primary tumor was performed five weeks (range=3-7 weeks) after mSC-RT. Nine patients underwent adjuvant chemotherapy. The median follow-up was 38.5 months. RESULTS: No patients developed grade ≥3 toxicities before surgery. Three patients developed local failures and 10 died during the follow-up period. The 1-, and 3-year local control rates were 91.7% and 71.3%, respectively. The median overall survival (OS) was 45.1 months. The 1-, and 3-year OS rates were 85.7% and 56.3%, respectively. Patients with stage IVA showed significantly better OS than those with stage IVB disease. CONCLUSION: mSC-RT followed by delayed surgery was well-tolerated and led to good local control in patients with rectal metastatic adenocarcinoma. mSC-RT could be a treatment option for patients with rectal metastatic adenocarcinoma as it is less likely to lead to cessation of systemic chemotherapy.

Protective Effect of Polaprezinc and Hyperbaric Oxygen Therapy on Radiation-induced Small Intestinal Damage in Mice.

BACKGROUND/AIM: To investigate the effect of polaprezinc (antioxidant) administration and hyperbaric oxygen therapy on radiation-induced intestinal injury. MATERIALS AND METHODS: Forty-five C57BL/6J mice underwent total body radiation of 2 Gy. Polaprezinc was given in 12 mice, hyperbaric oxygen in 12 mice, and both in 12 mice. The other 9 mice did not undergo any treatment. Mice were sacrificed 2, 4, and 6 h after radiation, and 9 specimens (3 each from the duodenum, jejunum, and ileum) were harvested. Apoptotic intestinal crypt cells were histologically evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. RESULTS: Apoptotic cell number per 1,000 crypt cells was 31.0±6.7 at 2 h, 28.4±5.2 at 4 h, and 32.9±5.1 at 6 h in the mice group treated by radiation alone. Both polaprezinc administration and hyperbaric oxygen therapy significantly suppressed apoptosis. Although the effect of polaprezinc administration on suppressing apoptosis became less over time (4.9±5.7 and 19.4±13.2 at 2 and 6 h, respectively), that of hyperbaric oxygen therapy was stable regardless of time (23.6±4.8 and 25.8±4.1 at 2 and 6 h). Administration of both polaprezinc and hyperbaric oxygen showed a significant synergetic or additive effect on suppressing apoptosis at 6 h (11.4±10.5, p<0.0035 vs. polaprezinc, p<0.0001 vs. hyperbaric oxygen). CONCLUSION: Both polaprezinc administration and hyperbaric oxygen therapy are effective in relieving radiation-induced small intestinal damage, and a synergistic or additive effect is expected when using both.

Radiation Pneumonitis After Volumetric Modulated Arc Therapy for Non-small Cell Lung Cancer.

BACKGROUND/AIM: To evaluate the incidence and grade of radiation pneumonitis after volumetric modulated arc therapy (VMAT) performed for the treatment of non-small cell cancer (NSCLC). PATIENTS AND METHODS: Fifty consecutive non-surgical candidates with NSCLC underwent VMAT. Thirty-five patients had stage-III tumors and 15 had recurrent tumors. The prescribed radiation dose for the gross tumor and the elective nodal area was 69 Gy in 30 fractions and 51 Gy in 30 fractions, respectively. RESULTS: Radiation pneumonitis developed in 38 patients (76%, 38/50), and grade ≥2 radiation pneumonitis developed in 11 patients (22%, 11/50). The percentage of lung volume that received a dose in excess of 5 Gy (V5), V10, V20, V30, and the mean lung dose (MLD) in the bilateral and ipsilateral lung were significantly associated with the development of grade ≥2 radiation pneumonitis. CONCLUSION: The incidence and degree of radiation pneumonitis are acceptable following treatment of NSCLC with VMAT.

Neoadjuvant Modified Short-Course Radiotherapy Followed by Delayed Surgery for Locally Advanced Rectal Cancer.

This study aimed to assess the clinical outcomes and predictive factors of neoadjuvant modified short-course radiotherapy (mSC-RT) for locally advanced rectal cancer (LARC). Data from 97 patients undergoing mSC-RT followed by radical surgery for LARC were retrospectively analyzed. A 2.5 Gy dose twice daily up to a total dose of 25 Gy in 10 fractions was administered through mSC-RT, and this was delivered with oral chemotherapy in 95 (97.9%) patients. Radical surgery was performed 6 (range, 3-13) weeks after mSC-RT. The median follow-up among surviving patients was 43 (8-86) months. All patients completed neoadjuvant radiotherapy with no acute toxicity grade ≥ 3. Three- and five-year local control rates were 96.3% and 96.3%, respectively. Three- and five-year overall survival (OS) rates were 92.7% and 79.8%, respectively. Univariate analyses revealed that poor OS was associated with no concurrent administration of capecitabine, C-reactive-protein-to-albumin ratio ≥ 0.053, carcinoembryonic antigen ≥ 3.4 ng/mL, and neutrophil-to-lymphocyte ratio (NLR) ≥ 1.83 (P = 0.045, 0.001, 0.041, and 0.001, respectively). Multivariate analyses indicated that NLR ≥ 1.83 was independently associated with poor OS (p = 0.018). mSC-RT followed by delayed surgery for LARC was deemed feasible and resulted in good clinical outcomes, whereas poor OS was associated with high NLR.

Influence of chemoradiotherapy on nutritional status in locally advanced rectal cancer: Prospective multicenter study.

OBJECTIVE: The aim of this study was to investigate the influence of chemoradiotherapy (CRT) on nutritional status and the association between changes in nutritional status and clinical outcomes (treatment completion, adverse events, perioperative complications, and relapse-free survival [RFS]) in patients with locally advanced rectal cancer (LARC). METHODS: In this multicenter, phase II study, 41 patients with LARC underwent CRT for 5 wk, followed by a 6- to 8-wk interval before surgery. Body weight, body mass index (BMI), lean body mass, serum albumin, and prealbumin levels were measured before (pre-), during, and after CRT, and before surgery. Changes in these data and scores on the Malnutrition Universal Screening Tool (MUST) were calculated based on pre-CRT status. RESULTS: Twelve patients (29.3%) experienced body weight loss (BWL) ≥5% (defined as malnutrition) after CRT (P < 0.001) and before surgery (P = 0.035). Significant changes were seen in serum albumin levels and BMI during and after CRT (P < 0.001), and in MUST scores after CRT (P = 0.003) and before surgery (P = 0.035). Treatment completion was significantly associated with BWL (P = 0.028), MUST score (P = 0.013), and decreased serum albumin level (P = 0.001) after CRT. Regarding adverse events, MUST score before surgery (P = 0.009) and serum albumin level after CRT (P = 0.002) were significantly associated with diarrhea severity. Serum albumin level during CRT was associated with the onset of neutropenia (P = 0.005). No association was found between BWL and RFS. CONCLUSIONS: These findings suggest that malnutrition and changes in nutritional status are not only commonly observed after CRT, but also associated with treatment completion and adverse events.

Japanese Structure Survey of Radiation Oncology in 2011.

We evaluated the evolving structure of radiation oncology in Japan in terms of equipment, personnel, patient load and geographic distribution to identify and overcome any existing limitations. From March 2012 to August 2015, the Japanese Society for Radiation Oncology conducted a questionnaire based on the Japanese national structure survey of radiation oncology in 2011. Data were analyzed based on the institutional stratification by the annual number of new patients treated with radiotherapy per institution. The estimated annual numbers of new and total (new plus repeat) patients treated with radiation were 211 000 and 250 000, respectively. Additionally, the estimated cancer incidence was 851 537 cases with approximately 24.8% of all newly diagnosed patients being treated with radiation. The types and numbers of treatment devices actually used included linear accelerator (LINAC; n = 836), telecobalt (n = 3), Gamma Knife (n = 46), 60Co remote afterloading system (RALS; n = 24), and 192Ir RALS (n = 125). The LINAC system used dual-energy functions in 619 units, 3D conformal radiotherapy functions in 719 and intensity-modulated radiotherapy (IMRT) functions in 412. There were 756 JRS or JASTRO-certified radiation oncologists, 1018.5 full-time equivalent (FTE) radiation oncologists, 2026.7 FTE radiotherapy technologists, 149.1 FTE medical physicists, 141.5 FTE radiotherapy quality managers and 716.3 FTE nurses. The frequency of IMRT use significantly increased during this time. To conclude, although there was a shortage of personnel in 2011, the Japanese structure of radiation oncology has clearly improved in terms of equipment and utility.

Improved error detection using a divided treatment plan in volume modulated arc therapy.

AIM: We sought to improve error detection ability during volume modulated arc therapy (VMAT) by dividing and evaluating the treatment plan. BACKGROUND: VMAT involves moving a beam source delivering radiation to tumor tissue through an arc, which significantly decreases treatment time. Treatment planning for VMAT involves many parameters. Quality assurance before treatment is a major focus of research. MATERIALS AND METHODS: We used an established VMAT prostate treatment plan and divided it into 12° × 30° sections. In all the sections, only image data that generated errors in one segment and those that were integrally acquired were evaluated by a gamma analysis. This was done with five different patient plans. RESULTS: The integrated image data resulting from errors in each section was 100% (tolerance 0.5 mm/0.5%) in the gamma analysis result in all image data. Division of the treatment plans produced a shift in the mean value of each gamma analysis in the cranial, left, and ventral directions of 94.59%, 98.83%, 96.58%, and the discrimination ability improved. CONCLUSION: The error discrimination ability was improved by dividing and verifying the portal imaging.

Surgical Risk and Survival Associated With Less Invasive Surgery for Malignant Pleural Mesothelioma.

We compared less invasive surgery with conventional surgery for malignant pleural mesothelioma (MPM). We retrospectively reviewed consecutive patients with MPM who received surgery at Hyogo College of Medicine between July 2004 and April 2016. Patients underwent multimodal treatment comprising chemotherapy (neoadjuvant and/or adjuvant) and surgery with or without 54 Gy hemithoracic radiotherapy. Patients were grouped into 3 groups according to the surgery intended: Conventional extrapleural pneumonectomy was intended in Group 1 (until August 2009); less invasive extrapleural pneumonectomy was intended in Group 2 (after September 2009); pleurectomy/decortication was intended in Group 3 (after September 2012). We included 152 patients (median age 64 [37-71] years; 131 men, 21 women), mostly with epithelioid subtypes (91.4%). Of them, 149 (98.0%) underwent neoadjuvant chemotherapy and 117 (77.0%) underwent surgery (60 had extrapleural pneumonectomy and 57 had pleurectomy/decortication). Macroscopic complete resection was achieved in 94.9% (111/117), and the mortality rates at 30 and 90 days were 1.7% (2/117) and 3.4% (4/117), respectively. The overall median survival time and progression-free survival for all 152 patients were 34.9 and 17.4 months. The overall median survival time for Groups 1, 2, and 3 were 18.5, 41.9, and 43.4 months, respectively. The progression-free survival for Groups 1, 2, and 3 were 12.0, 24.5, and 21.8 months, respectively. Compared with conventional surgical techniques, less invasive surgery for MPM yielded lower surgical risks and comparable or improved survival.

Japanese structure survey of radiation oncology in 2010.

We evaluated the evolving structure of radiation oncology in Japan in terms of equipment, personnel, patient load, and geographic distribution to identify and overcome any existing limitations. From March 2011 to June 2013, the Japanese Society for Radiation Oncology conducted a questionnaire based on the Japanese national structure survey of radiation oncology in 2010. Data were analyzed based on the institutional stratification by the annual number of new patients treated with radiotherapy per institution. The estimated annual numbers of new and total (new plus repeat) patients treated with radiation were 211 000 and 251 000, respectively. Additionally, the estimated cancer incidence was 805 236 cases, with ~26.2% of all newly diagnosed patients being treated with radiation. The types and numbers of treatment devices actually used included linear accelerator (LINAC; n = 829), telecobalt (n = 9), Gamma Knife (n = 46), 60Co remote afterloading system (RALS; n = 28), and 192Ir RALS (n = 131). The LINAC system used dual-energy functions in 586 units, three-dimensional conformal radiotherapy functions in 663, and intensity-modulated radiotherapy (IMRT) functions in 337. There were 564 JASTRO-certified radiation oncologists, 959.2 full-time equivalent (FTE) radiation oncologists, 1841.3 FTE radiotherapy technologists, 131.3 FTE medical physicists, 121.5 FTE radiotherapy quality managers, and 649.6 FTE nurses. The frequency of IMRT use significantly increased during this year. To conclude, although there was a shortage of personnel in 2010, the Japanese structure of radiation oncology has clearly improved in terms of equipment and utility.

Clinical T staging is superior to fluorodeoxyglucose positron emission tomography for predicting local outcomes after intra-arterial infusion chemoradiotherapy for maxillary sinus squamous cell carcinoma.

Concomitant intra-arterial infusion chemoradiotherapy (IA-CRT) has been used to treat locally advanced maxillary sinus squamous cell carcinoma (MSSCC) with positive outcomes. However, an optimal predictive prognostic factor for MSSCC treated with IA-CRT remains elusive. The aim of the present study was to assess the feasibility of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), including volumetric parameters, to predict the prognosis of MSSCC treated with IA-CRT. Twenty-four patients with newly diagnosed MSSCC receiving FDG-PET imaging before IA-CRT treatment were analyzed in this retrospective study. All patients underwent radiotherapy with a total tumor dose of 60-66 Gy in a conventional fractionation schedule, using three-dimensional conformal radiation therapy or intensity-modulated radiation therapy. Radiotherapy was performed concurrently with concurrent intra-arterial infusion chemotherapy (cisplatin). The IA-CRT response rate was 83.33%. The 1- and 3-year survival rates were 81.30% and 64.34%, respectively. The 1- and 3-year local failure-free rates were 57.21% and 40.96%, respectively. Local failure was significantly associated with poor survival (P = 0.0152). Further, clinical T staging clearly stratified local control outcomes among patients with clinical T3 or less, T4a, and T4b (P = 0.0312). Moreover, patients with stage T4b showed a significantly poorer local control compared with T3 or less (P = 0.0103). However, FDG-PET parameters provided no significant predictive information regarding treatment outcome. To conclude, pretreatment T stage predicts local control by IA-CRT, which is associated with survival.

The Potential Use of 11C-Choline Positron Emission Tomography/Computed Tomography to Monitor the Treatment Effects of Radium-223 in a Patient with Prostate Cancer.

We report here about a 59-year-old man with bone metastatic castration-resistant prostate cancer and biochemical progression, who underwent radium-223 (Ra-223) therapy, following previous treatment failure. Treatment response of osseous metastases was assessed with three 11C-choline positron emission tomography/computed tomography (PET/CT) scans at baseline, after three cycles for early monitoring, as well as after six cycles of radium-223 therapy. Pretreatment 11C-choline PET/CT showed multiple areas of increased focal activity in multiple cervical, thoracic, and lumbar vertebrae as well as in both ribs, right ileum, and left ischium. Second 11C-choline PET/CT after three cycles showed increasing tumor activity in the existing lesions and the new uptake spots of thoracic spine, both ribs and left ileum. Third 11C-choline PET/CT at the end of the therapy showed further progression with new lesions of thoratic spine, sacrum, right rib, and right ileum. In this case, 11C-choline PET/CT after three cycles for early monitoring could predict the therapeutic response to Ra-223.

Diagnostic Performance of 11C-choline PET/CT and FDG PET/CT in Prostate Cancer.

We compared 11C-choline and FDG PET/CT scan findings for the staging and restaging of prostate cancer. Twenty Japanese prostate cancer patients underwent 11C-choline and FDG PET/CT before (n=5) or after (n=15) treatment. Using a five-point scale, we compared these scanning modalities regarding patient- and lesion-based diagnostic performance for local recurrence, untreated primary tumor, and lymph node and bony metastases. Of the 20 patients, documented local lesions, and node and bony metastases were present in 11 (55.0%), 9 (45.0%), and 13 (65.0%), respectively. The patient-based sensitivity/specificity/accuracy/area under the receiver-operating-characteristic curve (AUC) values for 11C-choline-PET/CT for diagnosing local lesions were 90.9% /100%/ 95.0% / 1.0, whereas those for FDG-PET/CT were 45.5% /100%/ 75.0% / 0.773. Those for 11C-choline-PET/CT for node metastasis were 88.9% /100%/ 95.0% / 0.944, and those for FDG-PET/CT were 44.4%/100%/75.0%/0.722. Those for 11C-choline-PET/CT for bone metastasis were 84.6%/100%/90.0%/0.951, and those for FDG-PET/CT were 76.9% /100%/ 85.0% / 0.962. The AUCs for local lesion and node metastasis differed significantly (p=0.0039, p=0.011, respectively). The lesion-based detection rates of 11C-choline compared to FDG PET/CT for local lesion, and node and bone metastases were 91.7% vs. 41.7%, 92.0% vs. 32.0%, and 94.8% vs. 83.0% (p=0.041, p=0.0030, p<0.0001), respectively. 11C-choline-PET/CT is more useful for the staging and restaging of prostate cancer than FDG-PET/CT in Japanese men.

Pravastatin reduces radiation-induced damage in normal tissues.

Pravastatin is an inhibitor of 3-hydroxy-3-methyl- glutaryl-coenzyme A reductase that has been reported to have therapeutic applications in a range of inflammatory conditions. The aim of the present study was to assess the radioprotective effects of pravastatin in an experimental animal model. Mice were divided into two groups: The control group received ionizing radiation with no prior medication, while the pravastatin group received pravastatin prior to ionizing radiation. Pravastatin was administered orally at 30 mg/kg body weight in drinking water at 24 and 4 h before irradiation. Intestinal crypt epithelial cell survival and the incidence of apoptosis in the intestine and lung were measured post-irradiation. The effect of pravastatin on intestinal DNA damage was determined by immunohistochemistry. Finally, the effect of pravastatin on tumor response to radiotherapy was examined in a mouse mesothelioma xenograft model. Pravastatin increased the number of viable intestinal crypts and this effect was statistically significant in the ileum (P<0.0001). The pravastatin group showed significantly lower apoptotic indices in all examined parts of the intestine (P<0.0001) and tended to show reduced apoptosis in the lung. Pravastatin reduced the intestinal expression of ataxia-telangiectasia mutated and gamma-H2AX after irradiation. No apparent pravastatin-related differences were observed in the response of xenograft tumors to irradiation. In conclusion, pravastatin had radioprotective effects on the intestine and lung and reduced radiation-induced DNA double-strand breaks. Pravastatin may increase the therapeutic index of radiotherapy.

Utility of intraoral stents in external beam radiotherapy for head and neck cancer.

AIM: This study aimed to assess the utility and stability of intraoral stent during intensity-modulated radiation therapy (IMRT). BACKGROUND: The benefits of intraoral stents in radiotherapy are unclear. MATERIALS AND METHODS: We analyzed 386 setup errors in 12 patients who received IMRT for head and neck cancers without intraoral stents (intraoral stent [-]) and 183 setup errors in 6 patients who received IMRT with intraoral stents (intraoral stent [+]). All patients were matched according to the immobilization method (masks and boards). Setup errors were measured as the distance from the initial setup based on the marking on the skin and mask to the corrected position based on bone matching on cone beam computed tomography. RESULTS: The mean interfractional setup errors in the right-left, craniocaudal, anterior-posterior (AP), and three-dimensional (3D) directions were -0.33, 0.08, -0.25, and 2.75 mm in the intraoral stent (-) group and -0.37, 0.24, -0.63, and 2.42 mm in the intraoral stent (+) group, respectively (P = 0.50, 0.65, 0.01, and 0.02, respectively). The systematic errors for the same directions were 0.89, 1.46, 1.15, and 0.88 mm in the intraoral stent (-) group and 0.62, 1.69, 0.68, and 0.56 mm in the intraoral stents (+) group, respectively. The random errors were 1.43, 1.43, 1.44, and 1.22 mm in the intraoral stent (-) group and 1.06, 1.11, 1.05, and 0.92 mm in the intraoral stents (+) group, respectively. CONCLUSION: Setup errors can be significantly reduced in the AP and 3D-directions by using intraoral stents.

The impact of the radiation-induced regression of positive nodes on survival in patients with rectal cancer treated with chemoradiotherapy.

BACKGROUND: Although preoperative chemoradiotherapy exerts a destructive effect on positive lymph nodes, microscopic examination reveals different degrees of tumor regression. The aim of the present study is to investigate the impact of the radiation-induced regression of positive nodes on survival in patients with rectal cancer treated with preoperative chemoradiotherapy. METHODS: From 2001 to 2015, 229 patients with T3 rectal cancer underwent total mesorectal excision after preoperative chemoradiotherapy. The patients were classified into 3 groups according to their lymph node status: residual cancer cells in positive nodes (Group A), total regression of positive nodes after preoperative chemoradiotherapy with complete fibrosis (Group B), and the entire lymph node filled with lymph nodules and the absence of fibrosis (Group C). The survival of the 3 groups was compared, and a Cox model was used to evaluate the prognostic value of the regression of the positive nodes by preoperative chemoradiotherapy. RESULTS: Groups A, B, and C included 57, 18, and 154 patients, respectively. Group B showed significantly better overall survival than Group A (P = .041) and similar outcomes to Group C (P = .383). Among the patients with positive lymph nodes prior to treatment (Groups A and B), the total regression of the positive nodes after preoperative chemoradiotherapy was the only independent factor to be associated with good overall survival (hazard ratio; 6.26, 95% confidence interval; 1.28-113.0, P = .020). CONCLUSION: Total regression of positive nodes by preoperative chemoradiotherapy improves the prognosis of patients with rectal cancer with positive lymph nodes prior to treatment.

Polaprezinc protects normal intestinal epithelium against exposure to ionizing radiation in mice.

Polaprezinc (PZ), an antiulcer drug, has been reported to have antioxidant effects. The purpose of the present study was to assess the radioprotective effects of PZ in the normal intestine of C57BL/6J mice. PZ was orally administered at 100 mg/kg body weight in the drinking water. Firstly, the present study compared the survival of normal intestinal crypt epithelial cells with mice that received PZ prior to or following irradiation. Next, the present study examined the sequential changes of the incidence of apoptosis in the normal intestine of mice that received irradiation. The mice that received PZ prior to irradiation demonstrated a stronger protective effect on the normal intestine compared with those that received PZ after irradiation. The present study therefore administrated PZ 2 h before irradiation in the subsequent experiments. The mice receiving PZ developed fewer apoptotic cells in the duodenum, jejunum and ileum. Radiation-induced cell death occurred with a peak at position 10 or lower from the base of the crypt axis, and was subsequently reduced by PZ treatment. Pretreatment with PZ protected the normal intestinal tissues from radiation-induced apoptosis.

Radiotherapy in late elderly (aged 75 or older) patients with paranasal sinus carcinoma: a single institution experience.

The purpose of our study was to assess the feasibility of radiotherapy (RT) for locally advanced paranasal sinus carcinomas in late elderly patients (aged ≥75 years) from a single institution in Japan. From 2000 to 2015, we retrospectively analyzed 14 patients (11 maxillary and 3 ethmoid sinus carcinoma patients) who underwent RT for pathologically confirmed paranasal sinus carcinomas. RT was performed without unexpected cessations. Two patients, however, developed Grade 3 mucositis. The median follow-up duration was 13 months (range 2-54 months). The 1- and 2-year overall survival (OS) rates were 81.8 and 54.5 %, respectively. The local response rate after the initial treatment was 85.7 %. The 1- and 2-year progression-free survival (PFS) rates were 46.2 and 24.8 %, respectively. Univariate analysis of different clinicopathological parameters was conducted to identify associations with OS and PFS. We demonstrated that intensity modulated radiation therapy (IMRT) of >60 Gy with concomitant intra-arterial (cisplatin-based) infusion chemoradiotherapy led to improved OS and PFS rates, although no statistical significance was observed. Moreover, none of the squamous cell carcinoma (SCC) patients who received 33 fractions of 66 Gy in IMRT died during the median follow-up period of 13 months (range 12-25 months). In conclusion, RT with concomitant intra-arterial (cisplatin-based) infusion chemoradiotherapy can be considered an effective, well-tolerated, and feasible treatment option for late elderly patients with paranasal sinus carcinomas. In addition, >60 Gy of RT in IMRT led to improved survival outcomes in elderly paranasal sinus carcinoma patients.

A multicenter phase I study of preoperative chemoradiotherapy with S-1 and irinotecan for locally advanced lower rectal cancer (SAMRAI-1).

BACKGROUND AND PURPOSE: Preoperative 5-fluorouracil-based chemoradiotherapy is a standard treatment for locally advanced lower rectal cancer (LALRC). We performed a phase I study to develop a new regimen combining irinotecan and S-1. MATERIALS AND METHODS: Patients with LALRC (T3-4, N0-2) were studied. The radiation dose was 45Gy in 25 fractions. S-1 (80mg/m(2)/day) was administered on days 1-5, 8-12, 22-26, and 29-33. Irinotecan was administered on days 1, 8, 22, and 29. The dose of irinotecan was initially 60mg/m(2) (level 1). Surgery was performed 6-10weeks after the chemoradiotherapy. RESULTS: Twenty patients were enrolled, of whom 18 patients were analyzed. Dose-limiting toxicity (DLT) did not occur in the first 3 patients treated with irinotecan at 80mg/m(2) (level 2), but developed in 3 of the 6 patients who received irinotecan at 90mg/m(2) (level 3). Then DLT occurred in 3 other patients at level 2. At level 2 or 3, DLT comprised neutropenia, thrombocytopenia, and diarrhea. Level 2 was designated as the maximum tolerated dose, and level 1 as a recommended dose (RD). The pathological complete response rate was 28%, and the down-staging rate was 56%. CONCLUSIONS: Our results suggested that the RD of irinotecan when combined with preoperative S-1 and pelvic radiation was 60mg/m(2).

Trimodality strategy for treating malignant pleural mesothelioma: results of a feasibility study of induction pemetrexed plus cisplatin followed by extrapleural pneumonectomy and postoperative hemithoracic radiation (Japan Mesothelioma Interest Group 0601 Trial).

PURPOSE: We conducted a prospective multi-institutional study to determine the feasibility of trimodality therapy (TMT) comprising induction chemotherapy followed by extrapleural pneumonectomy (EPP) and radiation therapy in Japanese patients with malignant pleural mesothelioma (MPM). METHODS: Major eligibility criteria were histologically confirmed diagnosis of MPM, including clinical subtypes T0-3, N0-2, M0 disease; no prior treatment for the disease; age 20-75 years; Eastern Cooperative Oncology Group performance status 0 or 1; predicted postoperative forced expiratory volume >1000 ml in 1 s; written informed consent. Treatment methods comprised induction chemotherapy using pemetrexed (500 mg/m(2)) plus cisplatin (60 mg/m(2)) for three cycles, followed by EPP and postoperative hemithoracic radiation therapy (54 Gy). Primary endpoints were macroscopic complete resection (MCR) rate for EPP and treatment-related mortality for TMT. RESULTS: Forty-two eligible patients were enrolled: median age 64.5 (range 43-74) years; M:F = 39:3, clinical stage I:II:III = 14:13:15; histological type epithelioid were sarcomatoid; biphasic; others = 28:1:9:4. Of 42 patients, 30 completed EPP with MCR and 17 completed TMT. The trial met the primary endpoints, with an MCR rate of 71 % (30/42) and treatment-related mortality of 9.5 % (4/42). Overall median survival time and 2-year survival rate for 42 registered patients were 19.9 months and 42.9 %, respectively. Two-year relapse-free survival rate of 30 patients who completed EPP with MCR was 37.0 %. CONCLUSION: This phase II study met the predefined primary endpoints, but its risk/benefit ratio was not satisfactory.

Clinicopathological outcomes of preoperative chemoradiotherapy using S-1 plus Irinotecan for T4 lower rectal cancer.

PURPOSE: To investigate the clinicopathological outcomes of patients with T4 lower rectal cancer treated using preoperative chemoradiotherapy with S-1 plus Irinotecan. METHODS: Between 2005 and 2011, 35 patients with T4M0 lower rectal cancer, diagnosed initially as T4a in 12 and as T4b in 23, were treated with 45 Gy of radiotherapy concomitantly with S-1 plus Irinotecan. The median follow-up period was 50.6 months (range 2-123 months). RESULTS: A total of 32 patients (91.4 %) completed the radiotherapy and 26 (74.3 %) completed the full chemotherapy regimen. Radical surgery was then performed in 33 (94.3 %) of the 35 patients after the exclusion of two patients, who had macroscopic residual disease. The pathological diagnosis was downstaged from T4a to ypT0-3 in all 12 of those patients (100 %) and from T4b to ypT0-4a in 20 of those 23 patients (87.0 %). The tumor regression grade of 1a/1b/2/3 (complete response) was 10/8/15/2, respectively. In terms of long-term survival, the 5-year local relapse-free survival rate was 74.8 % and the recurrence-free survival rate was 52.0 %. CONCLUSIONS: This regimen may result in favorable downstaging. Moreover, in this series, pathological evidence of involvement of adjacent organs was rare following preoperative chemoradiotherapy, in the patients with disease diagnosed as T4b at the initial staging.