A Single-Arm Confirmatory Study of Definitive Chemoradiation Therapy Including Salvage Treatment for Clinical Stage II/III Esophageal Squamous Cell Carcinoma (JCOG0909 Study).

PURPOSE: Definitive chemoradiotherapy (CRT) is the standard treatment for patients with locally advanced esophageal cancer (EC) who refuse surgery as the initial therapy. However, poor survival, a high incidence of late toxicities, and severe complications after salvage surgery remain issues to be resolved. This single-arm multicenter trial (JCOG0909) aimed to confirm the efficacy of CRT modifications, including salvage treatment for reducing CRT-related toxicities and facilitating salvage treatment for improved survival. METHODS AND MATERIALS: Patients with clinical stage II/III EC (International Union Against Cancer sixth edition, non-T4) were eligible. Chemotherapy comprised cisplatin (75 mg/m2 on days 1 and 29) and 5-fluorouracil (1000 mg/m2/d on days 1-4 and 29-32). Radiation therapy was administered at a total dose of 50.4 Gy. Good responders received 1 to 2 additional cycles of chemotherapy. For residual or recurrent disease, salvage endoscopic resection or salvage surgery was performed based on specific criteria. The primary endpoint was 3-year overall survival (OS). The calculated sample size was 95 patients, with a 1-sided alpha of 5% and a power of 80%. The expected and threshold 3-year OS were 55% and 42%, respectively. RESULTS: Overall, 96 patients were enrolled, and 94 were included in the efficacy analysis. A complete response was achieved in 55 patients (59%). Salvage endoscopic resection and salvage surgery were performed in 5 (5%) and 25 patients (27%), respectively. R0 resection by salvage surgery was achieved in 19 patients (76%). Five patients (20%) showed grade 3 or 4 early operative complications, and 9 patients (9.6%) showed grade 3 late toxicities during the long-term follow-up. The 3-year OS was 74.2% (90% confidence interval, 65.9%-80.8%). CONCLUSION: The combination of definitive CRT and salvage treatment has lower CRT-related toxicities and yields good OS, thus making it a promising novel treatment option for patients with locally advanced EC.

The association of primary tumor site with acute adverse event and efficacy of definitive chemoradiotherapy for cStage II/III esophageal cancer: an exploratory analysis of JCOG0909.

BACKGROUND: JCOG0909 is a phase II trial of definitive chemoradiotherapy including salvage treatment for cStage II-III thoracic esophageal cancer; the radiation field for elective regional lymph node irradiation, which can affect patient outcome and adverse event, varied based on the primary tumor site, i.e., upper (Ut), middle (Mt), and lower thoracic (Lt) esophagus. The impact of different primary sites on the safety and efficacy of definitive chemoradiotherapy in JCOG0909 is not well characterized. METHODS: Patients were categorized into three groups (Ut, Mt, and Lt) according to the primary tumor location. We compared acute adverse events during definitive chemoradiotherapy, complete response (CR) rate, 3-year progression-free survival (PFS), and overall survival (OS) among the 3 groups. RESULTS: Out of the 96 patients enrolled in JCOG0909 between April 2010 and August 2014, 94 patients (16, 59, and 19 patients in the Ut, Mt, and Lt groups, respectively) were included in this exploratory analysis. The proportion of patients with cStage III was 25% in the Ut, 37% in the Mt, and 47% in the Lt group. Grade 3-4 leukopenia, neutropenia, and thrombocytopenia were more frequently observed in the Mt (66%, 54%, and 15%) and Lt groups (84%, 68%, and 16%) than in the Ut group (38%, 44%, and 0%). There was no significant between-group difference with respect to 3-year OS (73.3%, 77.9%, and 57.9%), 3-year PFS (60.0%, 59.3%, and 47.4%), or CR rate (62.5%, 62.7%, and 42.1%). CONCLUSIONS: In JCOG0909, the incidence of severe hematological toxicity had a trend toward higher in the Mt and Lt than the Ut esophageal cancer; however, no remarkable difference by primary sites was observed with respect to efficacy endpoints.

Impact of prophylactic cranial irradiation on pattern of brain metastases as a first recurrence site for limited-disease small-cell lung cancer.

This study sought to evaluate the impact of prophylactic cranial irradiation (PCI) on the pattern of brain recurrence after radical treatment in patients with limited-disease small-cell lung cancer (LD-SCLC). Patients treated with radiotherapy and chemotherapy between January 2006 and December 2014 at a single institution were retrospectively examined. Radiotherapy was performed using accelerated hyperfractionated radiotherapy (twice daily, 45 Gy in 30 fractions) or conventional fractionated radiotherapy (once daily, 50 Gy in 25 fractions). The chemotherapy regimen consisted of intravenous platinum-etoposide. A total of 162 patients were included and the median follow-up duration was 38 months. Ninety-three patients underwent PCI, and the 3-year overall survival (OS) rates were 14% among patients without PCI and 41% among those with PCI (P < 0.001). The frequency of brain metastases as a first recurrence site (BMFR) was significantly lower among patients who underwent PCI, compared with those who did not (P = 0.002). The median time to the l of BMFR was significantly shorter among patients without PCI than among those with PCI (P = 0.012). In addition, 68% of the BMFR patients who did not undergo PCI exhibited five or more lesions, while only 12% of BMFR patients who did undergo PCI exhibited five or more lesions (P < 0.001). PCI had a significant positive impact on patient prognosis after radical treatment for LD-SCLC, and the difference in the number of, and time to the appearance of, BMFR between patients treated with PCI and those treated without PCI might affect the clinical outcomes.

Late radiological changes after passive scattering proton beam therapy for Stage I lung cancer.

This study aimed to examine late radiological changes after proton beam therapy (PBT) for early-stage non-small cell lung cancer (NSCLC) and to clarify correlations between mass-like radiological changes and patient characteristics. CT scans of patients who underwent passive scattering PBT for T1-2N0M0 NSCLC were analyzed retrospectively. Patients were considered eligible if follow-up CT was performed for at least 2 years, with no definite evidence of local recurrence. The following five periods were defined: (i) 6-12 months, (ii) 12-24 months, (iii) 24-36 months, (iv) 36-48 months and (v) 48-60 months after PBT. Late (≥6 months) radiological changes were scored by consensus of three radiation oncologists according to classifications set forth by Koenig (Radiation injury of the lung after three-dimensional conformal radiation therapy. AJR Am J Roentgenol 2002;178:1383-8.). CT scans of 113 patients (median follow-up, 36 months; range, 24-137 months) were evaluated. Late radiological changes during Periods (i), (ii), (iii), (iv) and (v) included modified conventional pattern (80%, 79%, 72%, 58% and 56%, respectively), mass-like changes (8%, 9%, 14%, 22% and 18%, respectively), scar-like changes (4%, 9%, 11%, 17% and 24%, respectively) and no increased density (8%, 3%, 3%, 2% and 2%, respectively). Mass-like changes were observed in 23 patients (20%). Among patients who developed mass-like changes, the median interval between the initiation of PBT and the onset of mass-like changes was 19 months (range, 6-62 months). In multivariate analysis, a peripheral location was found to be a significant factor (P = 0.035; odds ratio: 4.44; 95% confidence interval: 1.12-21.28). In conclusion, mass-like changes were observed in 20% of patients who underwent PBT. Patients with peripheral tumors showed a higher incidence of mass-like changes.

Dosimetric comparison between proton beam therapy and photon radiation therapy for locally advanced esophageal squamous cell carcinoma.

BACKGROUND: The purpose of this study was to perform a dosimetric comparison between proton beam therapy (PBT) and photon radiation therapy in patients with locally advanced esophageal squamous cell carcinoma (ESCC) who were treated with PBT in our institution. In addition, we evaluated the correlation between toxicities and dosimetric parameters, especially the doses to normal lung or heart tissue, to clarify the clinical advantage of PBT over photon radiation therapy. METHODS: A total of 37 consecutive patients with Stage III thoracic ESCC who had received PBT with or without concurrent chemotherapy between October 2012 and December 2015 were evaluated in this study. The dose distributions of PBT were compared with those of dummy 3-dimensional conformal radiation therapy (3DCRT) and Intensity Modulated Radiation Therapy (IMRT), focusing especially on the doses to organs at risk, such as normal lung and heart tissue. RESULTS: Of the 37 patients, the data from 27 patients were analyzed. Among these 27 patients, four patients (15%) developed grade 2 pericardial effusion as a late toxicity. None of the patients developed grade 3 or worse acute or late pulmonary and cardiac toxicities. When the dosimetric parameters between PBT and planned 3DCRT were compared, all the PBT domestic variables for the lung dose except for lung V10 GyE and V15 GyE were significantly lower than those for the dummy 3DCRT plans, and the PBT domestic variables for the heart dose were also significantly lower than those for the dummy 3DCRT plans. When the PBT and IMRT plans were compared, all the PBT domestic variables for the doses to the lung and heart were significantly lower than those for the dummy IMRT plans. Regarding the correlation between the grades of toxicities and the dosimetric parameters, no significant correlation was seen between the occurrence of grade 2 pericardial effusion and the dose to the heart. CONCLUSIONS: When the dosimetric parameters of the dose distributions for the treatment of patients with locally advanced stage III ESCC were compared between PBT and 3DCRT or IMRT, PBT enabled a significant reduction in the dose to the lung and heart, compared with 3DCRT or IMRT.

Long-term results of S-1 plus cisplatin with concurrent thoracic radiotherapy for locally advanced non-small-cell lung cancer.

PURPOSE: The purpose of this phase I/II study was to evaluate the feasibility and efficacy of S-1 plus cisplatin at the recommended schedule with concurrent thoracic radiotherapy for locally advanced non-small cell lung cancer (LA-NSCLC). METHODS: Eligible patients with LA-NSCLC were treated with cisplatin intravenously at a dose of 60 mg/m2 on day 8 plus oral S-1 at a dosage of 40 mg/m2 twice per day for two different treatment schedules for up to 4 cycles. Patients also concurrently received 60 Gy of thoracic radiation in 30 fractions. The primary endpoint of the phase II study was the proportion of patients who survived for more than 2 years. RESULTS: Between August 2005 and October 2010, a total of 45 patients were enrolled in this phase I/II study; their long-term survival was then followed for a median period of 5.8 years. Nineteen of the 39 patients in the phase II study survived for more than 2 years and met the primary endpoint of the study. The median overall survival period was 24.9 months [95% confidence interval (CI) 17.4-74.5 months], and the 2- and 5-year overall survival rates were 51.0 and 43.0%, respectively. The response rate was 85%, and the median progression-free survival period was 13.8 months (95% CI 9.5-27.1 months). Hematological toxicity was mild. Grade 3 febrile neutropenia and pneumonitis was observed in 5 and 5%, respectively. CONCLUSION: Our study indicated that S-1 plus cisplatin with concurrent thoracic radiotherapy yielded encouraging survival outcomes and an acceptable safety profile for LA-NSCLC.

Salvage endoscopic resection (ER) after chemoradiotherapy for esophageal squamous cell carcinoma: What are the risk factors for recurrence after salvage ER?

BACKGROUND AND AIM: Salvage endoscopic resection (ER) is among the curative treatments for superficial local failure after chemoradiotherapy (CRT) for esophageal squamous cell carcinoma (ESCC). The present study aimed to clarify risk factors for recurrence after salvage ER. METHODS: This study enrolled consecutive ESCC patients treated with salvage ER for local failure after CRT between 1998 and 2013. Recurrences after salvage ER included locoregional recurrences and distant metastases. Multivariate analysis was carried out on clinicopathological parameters to identify risk factors for post-salvage ER recurrence. RESULTS: Of the 72 patients enrolled in this study, 37/8/23/4 patients had been staged before CRT as cT1/T2/T3/T4 and 44/28 patients as cN0/N1, respectively, and local failures detected before salvage ER were residual lesions after CRT in 19 and local recurrences in 53 patients. Resected specimens were classified as pT1a (M) in 45 and pT1b (SM) in 27 patients. During the median 45-month follow up (range, 3-175 months) after salvage ER, 27 (38%) patients developed recurrence with a 3-year recurrence-free survival rate of 48.9% (95% confidence interval [CI], 36.5-60.3). Multivariate analysis showed that residual lesions after CRT (HR, 2.55; 95% CI, 1.32-4.94) and lesions with a submucosal tumor (SMT)-like appearance before salvage ER (HR, 2.08; 95% CI, 1.04-4.18) were significantly associated with post-salvage ER recurrence. CONCLUSIONS: Clinical findings (e.g. residual tumors found immediately after CRT and macroscopic SMT-like appearance before salvage ER) were shown to be significant risk factors for post-salvage ER recurrence.

Long-term Clinical Results of Concurrent Chemoradiotherapy for Patients with Cervical Esophageal Squamous Cell Carcinoma.

BACKGROUND/AIM: We assessed the efficacy and toxicity of concurrent chemoradiotherapy (CCRT) in patients with squamous cell carcinoma of the cervical esophagus. PATIENTS AND METHODS: We retrospectively analyzed 37 patients treated with definitive CCRT. The patients received radiotherapy at a fraction dose of 2 Gy (total; 60 or 70 Gy) and concurrent chemotherapy. Adjuvant chemotherapy consisted of 1 to 2 cycles of 5-fluorouracil plus cisplatin or nedaplatin. RESULTS: The median follow-up was 119.0 months, the 10-year overall survival, progression-free survival and laryngectomy-free survival rates were 35.6, 19.9 and 30.2% respectively. In the univariate analysis, T stage (T4 vs. T1-3) was the only prognostic factor for PFS. The most common acute toxicity was leukocytopenia (Grade 3; 27%). As for late toxicities, 4 patients (11%) developed Grade 2 or 3 esophageal strictures. CONCLUSION: The results of this study demonstrated that CCRT yielded satisfactory clinical outcomes with acceptable toxicities.

Post-mastectomy radiation therapy without usage of a bolus may be a reasonable option.

To clarify the efficacy and toxicity of post-mastectomy radiation therapy (PMRT) without usage of a bolus, we identified 129 consecutive patients who received PMRT at the National Cancer Center Hospital East between 2003 and 2012. Seven of the 129 patients who received breast reconstruction before PMRT were excluded. All patients received PMRT of 6 MV photons, without usage of a bolus. The median follow-up duration for all eligible patients was 47.7 months (range: 4.0-123.2). Local, locoregional and isolated locoregional recurrence was found in 12 (9.8%), 14 (11%) and 5 patients (4.1%), respectively. The 3- and 5-year cumulative incidence of local recurrence, locoregional recurrence and isolated locoregional recurrence was 9.2 and 10.7%, 10.8 and 12.4%, and 4.3 and 4.3%, respectively. Although Grade 2 dermatitis was found in 11 patients (9.0%), no Grade 3-4 dermatitis was found. On univariate analysis, only a non-luminal subtype was a significant predictor for local recurrence (P < 0.001). On multivariate analysis, a non-luminal subtype remained as an independent predictor for local recurrence (P = 0.003, odds ratio: 10.9, 95% confidence interval: 2.23-53.1). In conclusion, PMRT without usage of a bolus resulted in a low rate of severe acute dermatitis without an apparent increase in local recurrence. PMRT without usage of a bolus may be reasonable, especially for patients with a luminal subtype.

Local efficacy and survival outcome of salvage endoscopic therapy for local recurrent lesions after definitive chemoradiotherapy for esophageal cancer.

BACKGROUND: Salvage endoscopic therapy (SET), such as endoscopic mucosal resection (EMR) and photodynamic therapy (PDT), is a less-invasive treatment for local failure at the primary site after chemoradiotherapy (CRT) for esophageal squamous cell carcinoma (ESCC). We conducted this retrospective study to clarify the risk factors for local recurrence along with the long term results after SET for recurrent lesions after definitive CRT for ESCC. METHODS: We enrolled 77 consecutive patients who underwent EMR or PDT for local recurrence without any metastasis after definitive CRT at our institution. We evaluated the local efficacy, local recurrence-free survival (LRFS), and overall survival (OS), and investigated the risk factors associated with survival outcome using a multivariate analysis. RESULTS: The complete resection rate of EMR was 84.6 % (33/39), and the complete response rate for PDT was 65.8 % (25/38). Twenty-two patients (28.6 %) exhibited local recurrence without metastasis. Thirty-four patients (44.2 %) were alive at 5 years after undergoing only initial SET or with repeated SET. The 5-year LRFS rate was 59.6 %, and the presence of lesions occupying an esophageal circumference of 1/4 or larger was the only significant risk factor (HR: 3.10, 95 % CI: 1.35-7.15, P = 0.008). The 5-year OS rate was 48.4 %, and an advanced T factor before CRT was marginally associated with a poor OS (HR: 1.96, 95 % CI: 0.98-3.92, P = 0.055). CONCLUSIONS: SET enabled a preferable local control and survival outcome for patients with local recurrence after definitive CRT for ESCC. Careful endoscopic follow-up is needed for patients with a large lesion before SET and those with an advanced T factor before CRT.

Salvage photodynamic therapy for local failure after chemoradiotherapy for esophageal squamous cell carcinoma.

BACKGROUND AND AIMS: Photodynamic therapy (PDT) is a less-invasive salvage treatment option for local failure at the primary site after chemoradiotherapy (CRT) for esophageal squamous cell carcinoma. The objective of this study was to clarify the long-term outcomes and prognostic factors of salvage PDT. METHODS: One hundred thirteen consecutive patients treated in our institution with PDT for local failure limited to within T2 without any metastases after definitive CRT performed between 1998 and 2008 were retrospectively enrolled. The complete response rate, adverse events, and survival outcomes were assessed and prognostic factors were investigated using a multivariate analysis. RESULTS: The complete response rate was 58.4% (95% confidence interval [CI], 49.3%-67.5%). The progression-free survival (PFS) and the overall survival (OS) rates at 5 years after salvage PDT were 22.1% (95% CI, 14.3%-30.0%) and 35.9% (95% CI, 26.7%-45.1%). N0 before CRT was significantly associated with OS (hazard ratio [HR], 0.54; 95% CI, 0.33-0.91, P = .020), whereas the impact of T1 or T2 before CRT on PFS (HR, 0.63; 95% CI, 0.38-1.04, P = .068) and that of a longer period between CRT and PDT on OS (HR, 0.64; 95% CI, 0.39-1.05, P = .078) were marginal. The treatment-related death rate was 1.8%. CONCLUSIONS: Salvage PDT was found to have a superior outcome and a satisfactory safety profile. An earlier clinical stage before CRT and a longer interval between CRT and PDT may be associated with a longer survival period.

Incidence and severity of adverse events associated with re-irradiation for spine or pelvic bone metastases.

BACKGROUND: Adverse events associated with re-irradiation for painful bone metastases have not been adequately evaluated. The purpose of this study was to clarify the incidence and severity of adverse events associated with re-irradiation for spine or pelvic bone metastases. METHODS: Data for 61 consecutive patients who required re-irradiation for spine or pelvic bone metastases between April 2009 and March 2013 were retrospectively evaluated in this study. The adverse events, biologically effective dose (BED), and the responses to pain and/or symptoms caused by cord compression were evaluated. RESULTS: Of the 61 patients, 52 were included in the study and their data were analyzed. The site of re-irradiation was the spine in 35 patients (67 %), and the pelvic bone in the remaining 17 patients (33 %). The median follow-up period was 170 days (range 5-1,644 days) for all eligible patients. The median interval from initial radiation therapy to re-irradiation was 161 days (range 26-2,909 days). The median cumulative BED from the initial radiation and re-irradiation was 115 Gy (range 80-155 Gy2). The acute adverse events were all below grade 2 in severity, except for two patients who showed grade 3 pain flare within a few days after the start of re-irradiation. No late adverse events were observed in this study that were grade 3 or of worse severity. CONCLUSIONS: The incidence and severity of adverse events after re-irradiation for spine or pelvic bone metastases were within acceptable limits in this study.

Accelerated radiotherapy for T1 to T2 glottic cancer.

BACKGROUND: Accelerated fractionation radiotherapy (RT) was administered in an attempt to improve the local control rates in patients with T1/T2 N0 glottic cancer. METHODS: Medical charts of 148 consecutive patients who had undergone RT using 2.4 Gray (Gy) once-daily fractionation between July 1999 and April 2007 were reviewed. RESULTS: Of 104 patients with T1 disease treated by RT, 82 received 60 Gy/25 fractions, and the remaining 22 with large tumor volumes and/or slow response to RT received 64.8 Gy/27 fractions. All 44 patients with T2 disease received 64.8 Gy/27 fractions. The 5-year local control and overall survival (OS) rates were 93% and 96%, respectively, in patients with T1 disease, and 77% and 91%, respectively, in patients with T2 disease. No severe acute toxicities were observed, although 2 patients (1%) developed severe late toxicity. CONCLUSION: Accelerated RT for early glottic cancer is feasible, with encouraging local control rates.

Retrospective analysis of risk factors for central nervous system metastases in operable breast cancer: effects of biologic subtype and Ki67 overexpression on survival.

OBJECTIVE: Identifying factors that predispose patients to central nervous system (CNS) metastases may hasten disease detection and improve treatment outcomes. METHODS: We reviewed the records of patients who were diagnosed with clinical stage I-III primary breast cancer at the National Cancer Center Hospital East from 2003 to 2005. Cox proportional hazard models were fitted to reveal risk factors for CNS metastases. RESULTS: The median follow-up period after the operation was 53.5 months. Among the 591 identified patients with breast cancer, 76 experienced a relapse. Seventeen patients developed CNS metastases. Multivariate analysis indicated that the triple negative (TN) subtype (hazard ratio = 5.5) and a high Ki67 labeling index (LI; hazard ratio = 3.9) were associated with a higher risk for CNS metastases. At 4 years, the TN subtype was associated with significantly worse overall and disease-free survival rates and a higher cumulative incidence of CNS metastases compared with hormone receptor-positive/ human epidermal growth factor receptor-2-negative tumors. Breast cancers with a Ki67 LI ≥30% were also associated with lower overall and disease-free survival rates and a higher cumulative incidence of CNS metastases compared with cancers with a Ki67 LI <30%. CONCLUSION: TN or Ki67-overexpressing breast cancer produced earlier CNS metastases and lower disease-free and overall survival rates.

Treatment strategy for superficial pharyngeal squamous cell carcinoma synchronously combined with esophageal cancer.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is often synchronously accompanied by pharyngeal squamous cell carcinoma (PSCC). However, treatment strategies for these synchronous cancers have not been established. AIM: To evaluate retrospectively the effects of both chemoradiotherapy (CRT) targeted for invasive ESCC on synchronous superficial PSCC and additional endoscopic resection (ER) for PSCC. PATIENTS AND METHODS: Screening endoscopy in the pharynx was performed in newly diagnosed ESCC patients. CRT combined with 5-fluorouracil (5-FU) and cisplatin (CDDP) was administered to all patients. The effect on superficial PSCC was only evaluated for 5-FU-CDDP chemotherapy that excluded the pharynx from the radiation field. When PSCC was remnant or recurrent in patients evaluated at complete response (CR) of ESCC, ER was performed on the PSCC. RESULTS: Fourteen cases of superficial PSCC (4.0%) were detected in 348 ESCC patients. Three PSCC reached CR in 8 ESCC-CR patients, while all 3 lesions recurred. No treatment response was found in the remaining 11 PSCC. As a second treatment, ER for 8 PSCC was completed in the 8 ESCC-CR patients, with one complication due to pneumonia. CONCLUSIONS: Standard 5-FU-CDDP CRT targeted for invasive ESCC did not demonstrate a sufficient efficacy for superficial PSCC, while ER even for PSCC after chemotherapy was curative.

Non-surgical approach to small cell carcinoma of the esophagus: does this rare disease have the same tumor behavior as SCLC?

BACKGROUND: We conducted a retrospective analysis to clarify the clinical profile of a nonsurgical approach to small cell carcinoma of the esophagus (SCEC). PATIENTS AND METHODS: SCEC patients in our database were reviewed. Consistent with the standard approach to small cell carcinoma of the lung (SCLC), chemoradiotherapy was the first choice for limited disease (LD)-SCEC in our institution while chemotherapy was the first choice for extensive disease (ED)-SCEC. Our strategy did not include prophylactic cranial irradiation. RESULTS: Eighteen patients were treated between January 1996 and December 2006, of whom 10 had LD-SCEC and 8 had ED-SCEC. Regarding response to chemoradiotherapy in patients with LD-SCEC, CR rate at the primary site was 90% (9/10) and total CR rate was 80% (8/10). With a median follow-up period of 55.3 months, median survival time in LD-SCEC and ED-SCEC patients was 17.3 and 13.9 months, respectively, showing no significant difference (p = 0.57). Brain metastases occurred in only one patient. On follow-up, eight patients with LD-SCEC and seven with ED-SCEC died of disease. Only 2 patients died of local progression, while the remaining 13 died of disease progression of distant metastases. CONCLUSION: Despite providing good local control, chemoradiotherapy appeared to have insufficient potential to cure LD-SCEC. Prophylactic brain irradiation for SCEC is unnecessary.

Efficacy of concurrent chemoradiotherapy as a palliative treatment in stage IVB esophageal cancer patients with dysphagia.

OBJECTIVE: To retrospectively assess the efficacy and safety of palliative chemoradiotherapy in Stage IVB esophageal cancer patients with dysphagia due to the primary lesion. METHODS: Forty patients with dysphagia caused by metastatic esophageal cancer, which had been treated between January 2004 and June 2009, were retrospectively investigated. The treatment consisted of two courses of chemotherapy (5-fluorouracil and cisplatin) and concurrent irradiation of 40 Gy in 20 fractions to the esophageal primary tumor. The grade of dysphagia was evaluated; nutrition-support-free survival was evaluated using the status of nutritional support of patients. Response to treatment, overall survival, progression-free survival and toxicities were also evaluated. RESULTS: Dysphagia score improved in 75% of the patients. Seventeen of the 20 patients (85%) who had required nutritional support at baseline improved their oral intake to no longer need the support, in a median time of 43 days. The median nutrition-support-free survival was 301 days in the 20 patients who had had adequate oral intake before the treatment. Disease control rate of the primary lesion was 95%, including 12 patients (30%) who achieved a complete response. The overall response rate was 55%. The median survival was 308 days, and the 1-year-survival rate was 45.0%. The median progression-free survival was 139 days. Toxicities were generally well tolerated. Major toxicities (Grade 3 or 4) involved hemoglobin (23%), leukocytes (15%), neutrophils (20%), anorexia (10%), nausea (3%), esophageal perforation (5%) and febrile neutropenia (3%). Two patients (5%) died within 30 days of terminating radiotherapy. CONCLUSIONS: Palliative chemoradiotherapy using 5-fluorouracil plus cisplatin combined with concurrent 40 Gy irradiation effectively improved the symptom of dysphagia in Stage IVB esophageal cancer with acceptable toxicity and favorable survival.

Multi-institutional Phase II study of proton beam therapy for organ-confined prostate cancer focusing on the incidence of late rectal toxicities.

PURPOSE: Proton beam therapy (PBT) is theoretically an excellent modality for external beam radiotherapy, providing an ideal dose distribution. However, it is not clear whether PBT for prostate cancer can clinically control toxicities. The purpose of the present study was to estimate prospectively the incidence of late rectal toxicities after PBT for organ-confined prostate cancer. METHODS AND MATERIALS: The major eligibility criteria included clinical Stage T1-T2N0M0; initial prostate-specific antigen level of ≤20 ng/mL and Gleason score ≤7; no hormonal therapy or hormonal therapy within 12 months before registration; and written informed consent. The primary endpoint was the incidence of late Grade 2 or greater rectal toxicity at 2 years. Three institutions in Japan participated in the present study after institutional review board approval from each. PBT was delivered to a total dose of 74 GyE in 37 fractions. The patients were prospectively followed up to collect the data on toxicities using the National Cancer Institute-Common Toxicity Criteria, version 2.0. RESULTS: Between 2004 and 2007, 151 patients were enrolled in the present study. Of the 151 patients, 75, 49, 9, 17, and 1 had Stage T1c, T2a, T2b, T2c, and T3a, respectively. The Gleason score was 4, 5, 6, and 7 in 5, 15, 80 and 51 patients, respectively. The initial prostate-specific antigen level was <10 or 10-20 ng/mL in 102 and 49 patients, respectively, and 42 patients had received hormonal therapy and 109 had not. The median follow-up period was 43.4 months. Acute Grade 2 rectal and bladder toxicity temporarily developed in 0.7% and 12%, respectively. Of the 147 patients who had been followed up for >2 years, the incidence of late Grade 2 or greater rectal and bladder toxicity was 2.0% (95% confidence interval, 0-4.3%) and 4.1% (95% confidence interval, 0.9-7.3%) at 2 years, respectively. CONCLUSION: The results of the present prospective study have revealed a valuable piece of evidence that PBT for localized prostate cancer can achieve a low incidence of late Grade 2 or greater rectal toxicities.

Proton beam therapy as a nonsurgical approach to mucosal melanoma of the head and neck: a pilot study.

PURPOSE: The aim of this pilot study was to assess the clinical benefit of proton beam therapy for mucosal melanoma of the head and neck. METHODS AND MATERIALS: Patients with mucosal melanoma of the head and neck with histologically confirmed malignant melanoma and N0 and M0 disease were enrolled. Proton therapy was delivered three times per week with a planned total dose of 60 Gy equivalents (GyE) in 15 fractions. RESULTS: Fourteen consecutive patients were enrolled from January 2004 through February 2008. Patient characteristics were as follows: median age 73 years old (range, 56 to 79 years); male/female ratio, 7/7; and T stage 1/2/3/4, 3/2/0/9. All patients were able to receive the full dose of proton therapy. The most common acute toxicities were mucositis (grade 3, 21%) and mild dermatitis (grade 3, 0%). As for late toxicity, 2 patients had a unilateral decrease in visual acuity, although blindness did not occur. No treatment-related deaths occurred throughout the study. Initial local control rate was 85.7%, and, with a median follow-up period of 36.7 months, median progression-free survival was 25.1 months, and 3-year overall survival rates were 58.0%. The most frequent site of first failure was cervical lymph nodes (6 patients), followed by local failure in 1 patient and lung metastases in 1 patient. On follow-up, 5 patients died of disease, 4 died due to cachexia caused by distant metastases, and 1 patient by carotid artery perforation cause by lymph nodes metastases. CONCLUSIONS: Proton beam radiotherapy showed promising local control benefits and would benefit from ongoing clinical study.

Elective nodal irradiation (ENI) in definitive chemoradiotherapy (CRT) for squamous cell carcinoma of the thoracic esophagus.

BACKGROUND AND PURPOSE: There are some reports indicating that prophylactic three-field lymph node dissection for esophageal cancer can lead to improved survival. But the benefit of ENI in CRT for thoracic esophageal cancer remains controversial. The purpose of the present study is to retrospectively evaluate the efficacy of elective nodal irradiation (ENI) in definitive chemoradiotherapy (CRT) for thoracic esophageal cancer. MATERIALS AND METHODS: Patients with squamous cell carcinoma (SCC) of the thoracic esophagus newly diagnosed between February 1999 and April 2001 in our institution was recruited from our database. Definitive chemoradiotherapy consisted of two cycles of cisplatin/5FU repeated every 5 weeks, with concurrent radiation therapy of 60 Gy in 30 fractions. Up to 40 Gy radiation therapy was delivered to the cervical, periesophageal, mediastinal and perigastric lymph nodes as ENI. RESULTS: One hundred two patients were included in this analysis, and their characteristics were as follows: median age, 65 years; male/female, 85/17; T1/T2/T3/T4, 16/11/61/14; N0/N1, 48/54; M0/M1, 84/18. The median follow-up period for the surviving patients was 41 months. Sixty patients achieved complete response (CR). After achieving CR, only one (1.0%; 95% CI, 0-5.3%) patient experienced elective nodal failure without any other site of recurrence. CONCLUSION: In CRT for esophageal SCC, ENI is effective for preventing regional nodal failure. Further evaluation of whether ENI leads to an improved overall survival is needed.