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Background: Small cell carcinoma of the esophagus is a rare malignant tumor. We aimed to explore the chemotherapeutic efficacy on the prognosis of patients with small cell carcinoma of the esophagus who received radiotherapy., Methods: To identify the population of interest, Surveillance, Epidemiology, and End Results data from 1996 to 2016 were chosen. Univariate and multivariate analyses were used to probe into prognosis factors. Multivariate Cox regression analysis was conducted to identify factors related to overall survival and cancer-specific survival., Results: Overall, data from 162 patients were analyzed in this study. Tumor size (P = 0.014), T staging (P = 0.028), and chemotherapy (P < 0.001) were independent prognostic factors affecting overall survival. Patients with regional disease (hazard ratio = 5.435, P < 0.001) and distant metastasis (hazard ratio = 2.183, P < 0.001) who received radiotherapy alone had worse survival than those receiving chemoradiotherapy. Tumor size (P = 0.004) and chemotherapy (P < 0.001) were independent prognostic factors affecting cancer-specific survival. Tumor size was an independent factor affecting cancer-specific survival for patients receiving chemoradiation., Conclusions: Age, T staging, tumor size, primary site, and chemotherapy are independent prognosis factors affecting overall survival and cancer-specific survival in patients with small cell carcinoma of the esophagus who receive radiotherapy. Chemotherapy might further improve cancer-specific survival in patients with small cell carcinoma of the esophagus receiving radiotherapy at all stages.

Background: Small cell carcinoma of the prostate is a rare condition with important differences from prostatic adenocarcinoma in terms of clinical and prognostic characteristics. A low prostate-specific antigen and a symptomatic patient, including paraneoplastic symptoms, characterize small cell carcinoma of the prostate. Diagnosis is made on the basis of prostate biopsy, and fluorodeoxyglucose positron emission tomography/computed tomography is often used for staging because up to 60% of patients present with de novo metastatic disease. Patients with metastatic disease are usually treated with platinum-based cytotoxic chemotherapy regimens similar to those used for small cell carcinoma of the lung. However, prognosis remains poor, with a median overall survival of 9 to 17 months despite therapy., Case Presentation: This report describes a case of an 80-year-old Caucasian patient with lymph node and bone metastatic small cell carcinoma of the prostate following low-dose-rate brachytherapy for a low-risk prostate carcinoma and treated with chemotherapy and immunotherapy., Conclusion: Low-dose-rate brachytherapy might be an etiology of small cell prostate cancer.

Background/aim: Primary small cell neuroendocrine carcinoma (SCNEC) of the adrenal gland is extremely rare with limited reports in the literature. There remain no definitive treatment guidelines, largely due to the rarity of the malignancy., Case Report: We present the case of a 62-year-old Caucasian male who presented with low back pain and was found to have a large retroperitoneal mass arising from the left adrenal gland, measuring 18.3 × 12.2 centimeters (cm). Biopsy was consistent with small cell carcinoma/high grade neuroendocrine carcinoma. Staging workup including CT chest and bone scan was negative. The patient was treated with chemotherapy, radiation therapy, and surgery; complete pathological response of the left adrenal tumor was achieved. Surveillance imaging every three months continued to show no evidence of recurrent disease., Conclusion: Primary SCNEC of the adrenal gland is rare and lacks standard treatment guidelines. Our case represents a possible treatment approach that may provide better clinical outcomes, however, further investigations are necessary to help define ideal treatment guidelines., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Unplanned hospitalization during cancer treatment is costly, can disrupt treatment, and affect patient quality of life. However, incidence and risks factors for hospitalization during lung cancer radiotherapy are not well characterized., Methods: Patients treated with definitive intent radiation (≥45 Gy) for lung cancer between 2008 and 2018 at a tertiary academic institution were identified. In addition to patient, tumor, and treatment related characteristics, specific baseline frailty markers (Charlson comorbidity index, ECOG, patient reported weight loss, BMI, hemoglobin, creatinine, albumin) were recorded. All cancer-related hospitalizations during or within 30 days of completing radiation were identified. Associations between baseline variables and any hospitalization, number of hospitalizations, and overall survival were identified using multivariable linear regression and multivariable Cox proportional-hazards models, respectively., Results: Of 270 patients included: median age was 66.6 years (31-88), 50.4% of patients were male (n = 136), 62% were Caucasian (n = 168). Cancer-related hospitalization incidence was 17% (n = 47), of which 21% of patients hospitalized (n = 10/47) had > 1 hospitalization. On multivariable analysis, each 1 g/dL baseline drop in albumin was associated with a 2.4 times higher risk of any hospitalization (95% confidence interval (CI) 1.2-5.0, P = 0.01), and baseline hemoglobin ≤10 was associated with, on average, 2.7 more hospitalizations than having pre-treatment hemoglobin > 10 (95% CI 1.3-5.4, P = 0.01). After controlling for baseline variables, cancer-related hospitalization was associated with 1.8 times increased risk of all-cause death (95% CI: 1.02-3.1, P = 0.04)., Conclusions: Our data show baseline factors can predict those who may be at increased risk for hospitalization, which was independently associated with increased mortality. Taken together, these data support the need for developing further studies aimed at early and aggressive interventions to decrease hospitalizations during treatment.

Background: Skin metastases from pancreatic neuroendocrine carcinoma (PNEC) are rare and their palliative treatment is challenging. We report our experience in the multimodal management of one of the few reported cases of metastatic PNEC with multiple visceral and subcutaneous secondary lesions, focusing on the effectiveness of palliative radiotherapy for skin metastases., Case Presentation: A 61-years old woman affected by a metastatic PNEC - with subcutaneous growing and bleeding secondary lesions (at the scalp, right scapular region and at the back of the left thoracic wall, respectively) - obtained a successful control of visceral metastases with the use of chemotherapy and an unexpected local response of her skin metastases with palliative radiotherapy. In particular, two subsequent radiation treatments were performed using different fractionation schedules (30 Gy in 10 fractions and 20 Gy in 5 fractions, respectively). Both radiation treatments were well-tolerated and patient's quality of life was improved. Local response was maintained until patient's death - that occurred due to cachexia., Conclusions: The presented case highlights the effectiveness and the good tolerance of radiotherapy in the treatment of subcutaneous metastases; nevertheless, further knowledge of the optimal local palliative approach for PNEC metastatic sites is necessary. The experience gained in this work is the occasion to encourage a routine integrated multidisciplinary team management of metastatic PNECs because of their clinical complexity. The aim is to guarantee the optimization of the care with personalized and more effective systemic and local treatments - also including supportive cares and treatment-related side effects management.

Background: Small cell carcinoma of the esophagus (SCCE) is characterized by its progressive feature and poor prognosis. There is no consensus on a standard therapeutic modality for SCCE. In this study, we aimed to characterize the outcomes of primary SCCE patients treated by radiation therapy as part of treatment and investigate prognostic factors., Methods: We retrospectively analyzed the data of 42 SCCE patients who were treated by RT as part of treatment at the Sun Yat-sen University Cancer Center from 2001 to 2014. The Kaplan-Meier and log-rank method were used to analyze survival. Cox's hazard regression model was applied to determine prognostic factors., Results: Of the 42 enrolled patients, 25 had limited disease (LD) and 17 with extensive disease (ED). The overall response rate (CR + PR) was 60.0% (21/35). The median overall survival time (OS) for whole and LD group were 12.9 and 36.8 months. The 1-, 3- and 5-year OS rates of the whole cohort were 64.9, 31.3, and 13.9%, respectively. OS was significantly longer in patients with ECOG performance score (ECOG PS) < 2 (p = 0.001), lesion length ≤ 5 cm (p = 0.001), and LD (p = 0.049). In the patients with LD, multivariate analysis indicated that combined with chemotherapy (P = 0.046) and higher radiation dose (P = 0.027) predicted better prognosis in OS. The overall rate of grade 3-4 toxicities in the whole cohort was 37.5%. In total, 65% (17/26) patients with recurrent disease died with the metastasis with or without the primary recurrence., Conclusion: RT was one of the effective and safe treatments for locoregional control of SCCE. Lower ECOG PS score, shorter lesion length, treated with chemotherapy, and a higher dose of RT were identified as favorable independent prognostic factors.

Objective: To determine the prognostic effect of adjuvant radiation and clinicopathological variables in surgically treated patients with small cell carcinoma of the cervix (SCCC)., Methods: Clinical data of SCCC patients with International Federation of Gynaecology and Obstetrics (FIGO) stage I-II underwent radical surgery from May 2000 to August 2014 at Sun Yat-sen Memorial Hospital were retrospectively reviewed. Forty-three patients with SCCC were included to this study. Chi-square test or Fisher's exact test, Student's t test or Mann-Whitney U test, Kaplan-Meier method and multivariate analysis of Cox proportional hazards regression were used for statistical analysis. P < 0.05 was considered to be statistically significant., Results: Among 43 patients (median age, 49 years old) recruited, 25(58.1%) had stage I, 18(41.9%) had stage II disease. The 5-year overall survival (OS) rate was 39.54%, and the 5-year disease free survival (DFS) was 27.91%. Distant metastasis was the main cause of treatment failure (71.9%). Patients with adjuvant chemoradiation displayed lower rate of local recurrence than those with adjuvant chemotherapy (10.7% vs 60.0%, P < 0.0001). Multivariable analysis identified lymph node metastasis as a significant prognostic factor for both DFS and OS (P = 0.001, 0.004 respectively). Age was also an independent predictor of OS (P = 0.004). Adjuvant radiation appeared to significantly improve DFS (HR = 0.383, 95% CI, 0.185-0.791), but not OS., Conclusions: Adjuvant radiotherapy could improve the local control and prolong DFS in surgically treated SCCC. However, a large prospective clinical trial is needed to confirm this.

Small cell carcinoma of the bladder is extremely rare, accounting for <1% of all malignant tumours in the urinary tract. Thus, no standard therapy modality for this malignancy has been established. This study aimed to retrospectively analyse the clinical outcomes associated with definitive radiotherapy for small cell carcinoma of the bladder. A questionnaire-based survey of patients with pathologically proven small cell carcinoma of the bladder treated with definitive radiation therapy between 1990 and 2010 was conducted by the Japanese Radiation Oncology Study Group. The clinical records of 12 eligible patients were collected from nine institutions. The median age of the patients was 70.5 years (range: 44-87 years), and the median follow-up period was 27.3 months (range: 3.3-117.8 months). The median prescribed dose was 60 Gy (range: 50.0-61.0 Gy), and a median of 2.0 Gy (range: 1.2-2.0 Gy) was administered per fraction. Systemic chemotherapy combined with radiotherapy was performed in eight cases (66.7%). The 3- and 5-year overall survival rates were 50.0% and 33.3%, respectively. And the 3- and 5-year local control rates were 66.7% and 55.6%, respectively. Chemotherapy significantly improved overall survival and relapse-free survival (P = 0.006 and 0.001, respectively). No serious adverse events occurred in the observation period. All patients who achieved local control maintained functional bladders. In conclusion, radiotherapy is a potential local treatment option and has an important role in maintaining quality of life. Systemic chemotherapy combined with local radiotherapy seems to be effective in improving survival., (© The Author(s) 2019. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

Small cell carcinoma (SmCC) of the vagina is a rare and aggressive tumour. It comprises only 1% -2% of all gynaecological malignancies 85% of the patients with SmCC vagina die within a year of diagnosis. Here we report the case of a 65-year-old woman with stage III primary neuroendocrine carcinoma of vagina who was treated with chemoradiotherapy. The patient survived 1 year and 10 months after the initial presentation. SmCC of the vagina is very rare and despite being aggressive, the local disease can be controlled with a chemoradiation regimen., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: While external beam radiotherapy boost has been one of the standard management options for locally advanced cervical cancer that is not treatable with intracavitary brachytherapy, its efficacy remains unclear. We assessed clinical outcomes in Japanese patients with cervical cancer who underwent external beam radiotherapy alone and identified related prognostic factors., Methods: Patients treated with definitive external beam radiotherapy for cervical cancer unsuitable for intracavitary brachytherapy, including whole pelvic irradiation and external beam radiotherapy boost, were retrospectively examined. The endpoints were progression-free survival, overall survival and adverse events. Additionally, various patient-, tumor- and treatment-specific factors were evaluated to identify significant predictors of progression-free survival., Results: The study included 37 patients; 3 (8%), 5 (14%), 17 (46%) and 12 (32%) had clinical International Federation of Gynecology and Obstetrics (FIGO) stages I, II, III and IVA, respectively. A total radiation dose of 56-70.2 Gy was administered (84% of patients received 59.4-60.4 Gy). The median follow-up period after radiotherapy was 17 (range, 2-84) months. The progression-free survival rates at 1 and 2 years were 45 and 29%, respectively; the corresponding overall survival rates were 74 and 43%, respectively. On univariate and multivariate analyses of progression-free survival at 2 years, International Federation of Gynecology and Obstetrics stage IVA and a maximum primary tumor diameter >5 cm were associated with significantly worse outcomes (P = 0.026 and P = 0.027, respectively)., Conclusion: Approximately 70% of patients with cervical cancer treated with external beam radiotherapy boost instead of intracavitary brachytherapy experienced disease progression within 2 years. These results stress the necessity of devising alternative non-intracavitary brachytherapy treatment approaches, particularly for patients with International Federation of Gynecology and Obstetrics stage IVA and bulky primary tumors., (© The Author(s) 2018. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: To describe the clinical characteristics, treatment patterns, and outcomes in patients with small cell bladder cancer at our institution, including those who received prophylactic cranial irradiation (PCI) for the prevention of intracranial recurrence., Materials and Methods: Patients with small cell bladder cancer treated at a single institution between January 1990 and August 2015 were identified and analyzed retrospectively for demographics, tumor stage, treatment, and overall survival., Results: Of 44 patients diagnosed with small cell bladder cancer, 11 (25%) had metastatic disease at the time of presentation. Treatment included systemic chemotherapy (70%), radical surgery (59%), and local radiation (39%). Six patients (14%) received PCI. Median overall survival was 10 months (IQR 4 - 41). Patients with extensive disease had worse overall survival than those with organ confined disease (8 months vs. 36 months, respectively, p = 0.04). Among those who received PCI, 33% achieved 5 - year survival., Conclusion: Outcomes for patients with small cell bladder cancer remain poor. Further research is indicated to determine if PCI increases overall survival in small call bladder cancer patients, especially those with extensive disease who respond to chemotherapy., Competing Interests: None declared., (Copyright® by the International Brazilian Journal of Urology.)

Background/aims: To evaluate the clinicopathologic aspects of small cell neuroendocrine carcinoma of the uterine cervix (SCNEC)., Methods: A retrospective review of 40 patients with SCNEC in 3 hospitals from 2009 to 2015 was conducted to assess the survival rates and examine the associations between clinicopathological variables and overall survival (OS). A meta-analysis of 22 studies containing 1901 patients was also conducted to further confirm the results., Results: In the clinical group of 40 patients, the 5-year OS rate was 20%. Advanced International Federation of Gynecology and Obstetrics (FIGO) stage and radiation therapy (RT) were associated with poor survival. However, radical surgery was associated with prolonged survival. In the meta-analysis of 1901 patients, the 2-year disease-free survival (DFS) rate, 5-year DFS rate, 2-year OS rate, 3-year OS rate and 5-year OS rate of SCNEC were 48%, 35%, 62%, 35%, and 35% respectively. Advanced FIGO stage, larger tumor size, lymph node metastasis (LNM) (+), lymphovascular space involvement (LVSI) (+), parametrial involvement (PI) (+), depth of stromal invasion (DSI) > 2/3, and RT were associated with poor survival. However, a chemotherapy regimen similar to that for small cell lung cancer was associated with prolonged survival., Conclusion: Advanced FIGO stage, larger tumor size, LNM (+), LVSI (+), DSI > 2/3, PI (+), and RT were independent predictors of poor prognosis of SCNEC. Radical surgery combined with a chemotherapy regimen similar to that of small cell lung cancer may be a potential therapeutic approach for SCNEC., (© 2018 The Author(s). Published by S. Karger AG, Basel.)

Despite administration of prophylactic cranial irradiation (PCI), some small cell lung cancer (SCLC) patients still suffer from brain metastases (BM) with unknown risk factors. We conducted this study to identify patients with higher BM risk after PCI and improve their outcome. The characteristics and survival of all the SCLC patients underwent PCI in our institute from 2003 to 2014 were analyzed. Kaplan-Meier method was applied to estimate BM free survival (BMFS) and overall survival (OS). Cox regression analyses were performed to explore risk factors for BM. A total of 175 patients with the median age of 55 years (range, 29-76) were eligible, among whom 36 (20.6%) developed BM with median follow-up of 42 months. Both univariate and multivariate analyses showed HART and TNM classification (p < 0.05) were associated with BM. Two-stage system was not related with BMFS or OS (p > 0.05). Stage IIIB-IV and HART were independent risk factors for BM after PCI in SCLC. TNM classification was more valuable on prognosis than two-stage system. Further large-scale studies are needed to confirm our findings.

Background and Aims: Small cell esophageal carcinoma (SCEC) is a rare malignant tumor. So far, few studies are found to research the effect of radiotherapy (RT) to it. This study is designed to explore the prognostic factors, and analyze survival benefit of RT to patients with SCEC., Results: Patients with SCEC were more likely to be in female, older, higher disease stage than those with non-small cell esophageal carcinoma. RT was used in more than 50% SCEC patients. RT tended be reduced as the disease stage raise in SCEC. Univariate and multivariate analysis showed that age, year, disease stage, and RT were the prognostic factors of survival (P < 0.05). RT reduced nearly 75% risks of death in localized stage (P < 0.05), nearly 50% risks of death in regional stage (P > 0.05) and nearly 30% risks of death in distant stage (P > 0.05)., Methods: SCEC patients between 1973 and 2012 were searched from the Surveillance Epidemiology and End Results (SEER) data. Clinical factors including age, year, sex, race, stage, surgery, and RT were summarized. Univariate and multivariate analysis were performed to explore the independent prognostic factors of SCEC. Cox regression survival analysis was performed to evaluate the effect of RT to SCEC based on different stages., Conclusions: Stage, age, year, and RT are independent prognostic factors of SCEC. Survival benefit of RT exists in any disease stage, but is only statistically significant in localized stage of SCEC.

Background: Small cell carcinoma of the rectum is a rare neoplasm with scant literature to guide treatment. We used the Surveillance Epidemiology and End Results (SEER) database to investigate the role of radiation therapy in the treatment of this cancer., Methods: The SEER database (National Cancer Institute) was queried for locoregional cases of small cell rectal cancer. Years of diagnosis were limited to 1988-2010 (most recent available) to reduce variability in staging criteria or longitudinal changes in surgery and radiation techniques. Two month conditional survival was applied to minimize bias by excluding patients who did not survive long enough to receive cancer-directed therapy. Patient demographics between the RT and No&#95;RT groups were compared using Pearson Chi-Square tests. Overall survival was compared between patients who received radiotherapy (RT, n = 43) and those who did not (No&#95;RT, n = 28) using the Kaplan-Meier method. Multivariate Cox proportional hazards model was used to evaluate important covariates., Results: Median survival was significantly longer for patients who received radiation compared to those who were not treated with radiation; 26 mo vs. 8 mo, respectively (log-rank P = 0.009). We also noted a higher 1-year overall survival rate for those who received radiation (71.1% vs. 37.8%). Unadjusted hazard ratio for death (HR) was 0.495 with the use of radiation (95% CI 0.286-0.858). Among surgery, radiotherapy, sex and age at diagnosis, radiation therapy was the only significant factor for overall survival with a multivariate HR for death of 0.393 (95% CI 0.206-0.750, P = 0.005)., Conclusions: Using SEER data, we have identified a significant survival advantage with the use of radiation therapy in the setting of rectal small cell carcinoma. Limitations of the SEER data apply to this study, particularly the lack of information on chemotherapy usage. Our findings strongly support the use of radiation therapy for patients with locoregional small cell rectal cancer.

Background: To investigate the role of radiotherapy (RT) in and to suggest radiotherapeutic strategies for patients presenting with disseminated cervical cancer., Methods: We retrospectively analyzed 50 patients diagnosed as the disseminated cervical cancer with distant lymph nodal or visceral organ metastasis between September 1980 and August 2012. Patients were divided into two subgroups according to visceral organ metastasis: 35 patients diagnosed with distant lymph node metastasis only (group A) and 15 patients with visceral organ metastasis (group B). All patients received external beam RT to the pelvis (median dose 45 Gy) and high-dose rate intracavitary RT (median dose 30 Gy). Thirty-nine patients (78%) received chemotherapy., Results: Median follow-up time was 74 months. The 5-year pelvic control rate (PCR) was 85.8%, and the progression-free survival (PFS), and overall survival (OS) rates were 28.7%, and 36.2%, respectively. The major treatment failure was systemic progression (32 patients, 64%). The 5-year PCRs in groups A and B were 87.4% and 74.7%, respectively (p > 0.05). Meanwhile, PFS and OS rates for group A were significantly better than those for group B (35.3% vs. 13.3%, p = 0.010; and 46.3% vs. 13.3%, p = 0.009, respectively)., Conclusion: Our data revealed considerable prognostic heterogeneity in disseminated cervical cancer. Even though a high PCR was achieved in patients treated with definitive RT, survival outcomes were dependent on progression of visceral organ metastasis. Therefore, personalized RT and chemotherapy treatment strategies according to the presence of visceral organ metastasis in disseminated cervical cancer patients may help improve clinical outcomes.

A 74-year-old man was diagnosed with small cell carcinoma arising from the extrahepatic bile duct according to a histological examination of the biopsy specimen obtained during endoscopic retrograde cholangiopancreatography. Additionally, bulky hilar lymphadenopathy was observed, and the patient was treated with the combination of radiation and chemotherapy (cisplatin and irinotecan). Post-therapy, he underwent pancreaticoduodenectomy. The histological examination of the resected specimen revealed no residual cancer cells in the bile duct wall and a small amount of cancer cells in only a single lymph node. Due to this multidisciplinary therapy, the patient showed no signs of recurrence 12 months postoperatively.

Aims: Few studies have examined the clinical characteristics of patients with brain metastases from small-cell esophageal cancer. In this study, we review the clinical characteristics and outcomes in patients with brain metastases from small-cell esophageal cancer., Patients and Methods: From August 2002 to August 2012, consecutive patients diagnosed with brain metastases from small-cell esophageal cancer and treated with radiotherapy were enrolled. Clinical features, diagnostic findings, and survival were analyzed., Results: Six patients treated with brain radiotherapy were identified. The median age was 64 (range 61-74) years. All patients had neurological impairments. Three patients had supra- and infra-tentorial metastases, and three patients had cerebrum metastases. Brain metastases were detected when esophageal cancer was initially diagnosed in two patients. In three patients, magnetic resonance imaging findings after radiotherapy confirmed a significant response to treatment. The median overall survival was 6.0 months. During the same period, 43 patients with squamous cell carcinoma and seven patients with adenocarcinoma who had brain metastases were identified. Survival periods for squamous cell carcinoma and adenocarcinoma patients who had brain metastases were 5.5 months and 4.2 months, respectively. There was no significant difference in overall survival according to the histological type., Conclusions: Brain metastases from small-cell esophageal cancer tend to spread to the cerebellum and impair patients' quality-of-life. Brain radiotherapy had a positive effect in this case series; however, overall survival remains short.

Background: Primary small cell carcinoma of the esophagus (SCCE) is characterized as highly aggressive with a poor prognosis. To identify potential prognostic factors and to assess the role of surgical procedures, chemotherapy, and radiotherapy for SCCE, we retrospectively analyzed patients with SCCE from three large institutions in China., Methods: All of the SCCE patients between 1998 and 2012 were identified from three clinical databases of the Sun Yat-Sen University Cancer Center, Peking Union Cancer Hospital and Shantou Cancer Hospital. Potential prognostic factors were analyzed with univariate analysis and a Cox regression model. Subgroup analysis based on the 2002 American Joint Committee on Cancer staging system for esophageal cancer was applied to examine the effect of treatment on survival., Results: In patients with stage I/II SCCE, 85% underwent operations and showed improved survival (median survival time [MST] 29 vs 17.4 months, p = 0.082). However, chemotherapy did not further improve survival. In patients with stage IIB/III SCCE, chemotherapy, instead of operation, improved survival (MST 13.0 vs 6.1 months, p = 0.003), and radiotherapy resulted in improved survival. In stage IV patients, chemotherapy improved survival (MST 12.5 vs 4.0 months, p < 0.001), and chemotherapy combined with radiotherapy was superior to chemotherapy alone (MST 13.2 vs 8.9 months, p = 0.014)., Conclusions: Surgical procedures alone can be recommended for stage I/IIA patients. In patients with stage IIB disease or above, chemotherapy should be the main treatment approach, and chemotherapy combined with radiotherapy tended to improve survival., (Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: As clinical trials for limited-disease small-cell lung cancer often exclude elderly patients due to comorbidities and a decline in organ function, the most suitable treatment for limited-disease small-cell lung cancer patients aged 75 years or older still remains unclear., Methods: From July 2002 to June 2011, 20 consecutive patients aged 75 years or older, with Stage II to IIIB limited-disease small-cell lung cancer, were scheduled to be treated with concurrent or sequential chemoradiotherapy at the Shizuoka Cancer Center. We reviewed the medical charts of the patients and evaluated their characteristics, treatment compliance, toxicity and antitumor efficacy., Results: Five patients were treated with concurrent chemoradiotherapy and the other 15 patients were scheduled to be treated with sequential chemoradiotherapy. Of these 15 patients, 12 were treated with four cycles of etoposide (80 mg/m(2), days 1-3, q3-4w) plus carboplatin (area under the curve 5, day 1, q3-4w), followed by thoracic radiotherapy. Of the five patients treated with concurrent chemoradiotherapy, discontinuation of chemotherapy/thoracic radiotherapy occurred in two patients due to toxicity and they suffered a prolonged decrease in performance status. Of the 12 patients treated with etoposide plus carboplatin followed by sequential thoracic radiotherapy, the response rate, median progression-free survival and median overall survival time were 91%, 244 and 601 days., Conclusions: These results suggest that concurrent chemoradiotherapy is not feasible for all limited-disease small-cell lung cancer patients aged 75 years or older. The alternative of four cycles of etoposide plus carboplatin followed by thoracic radiotherapy is a candidate for the standard treatment of limited-disease small-cell lung cancer patients in this age group. A further trial is warranted to develop and evaluate the optimal treatment for elderly patients with limited-disease small-cell lung cancer.

Small cell carcinoma of the uterine cervix (SCCC) is a rare subtype of cervical cancer with an aggressive behavior. Although SCCC has a worse prognosis than other histological types of uterine cervical cancer such as squamous cell carcinoma or adenocarcinoma, standard therapy for SCCC remains to be established due to its rarity. The purpose of this study was to evaluate the efficacy and toxicity of concurrent chemoradiotherapy (CCRT) using a regimen consisting of vincristine, adriamycin, and cyclophosphamide alternating with cisplatin and etoposide (VAC/PE). We analyzed a series of 9 patients with SCCC. Five patients with stage IB disease underwent radical hysterectomy followed by CCRT. Four patients with advanced stage disease received CCRT primarily. With a median follow-up duration of 47.4 months (range, 10.5 to 86.4 months), 4 out of 5 patients with stage IB disease were alive without recurrence. In 4 patients with advanced stage disease, the response rate was 75% (complete response, 1; partial response, 2; progressive disease, 1). One patient with stage IVB disease remained without recurrence for 89.5 months. At 5 years, overall survival (OS) and progression-free survival for all patients was 52% and 56%, respectively. Patients with early-stage disease had an 80% 5-year OS rate compared to 25% for patients with advanced stage disease. Although all patients developed grade 3-4 neutropenia, CCRT using VAC/PE is feasible in both the primary and adjuvant settings for SCCC. In particular, this combined modality therapy may improve both local control and survival as postoperative treatment in patients with early-stage disease.

Small cell carcinoma of the gastrointestinal tract is rare, and no effective strategy has yet been established. On the basis of regimens reportedly effective for small cell lung cancer, we performed chemotherapy with cisplatin plus etoposide in combination with radiotherapy to relieve obstruction, in a patient with small cell carcinoma of the gastro-oesophageal junction. Chemotherapy was switched to carboplatin plus etoposide due to renal toxicity. No distant metastases were detected and lesion spread was limited. A complete response, with no evidence of recurrence to date, was achieved. Curative resection was suggested but refused by the patient. He has been closely followed up in our outpatient clinic for more than a year and has shown no evidence of recurrence since the completion of treatment. Although cisplatin plus etoposide is a standard chemotherapy regimen for small cell carcinoma, carboplatin plus etoposide may be effective in cases in which cisplatin is contraindicated due to renal toxicity.

The study was performed to evaluate radiotherapy for patients with intramedullary spinal cord metastasis (ISCM) and to identify the clinical features of ISCM. The subjects were 18 patients (8 men, 10 women) with ISCM who underwent radiotherapy between September 2002 and February 2008. The primary lesions were lung cancer in 8 patients (2 small cell, 6 non-small cell), breast cancer in 6, malignant melanoma in 2, renal cell carcinoma in 1, and rectal cancer in 1 patient. Diagnosis, symptoms and survival of these patients were compared with those for 544 patients with vertebral metastases who underwent radiotherapy at the same institute between September 2002 and November 2006. In the 18 patients with ISCM, the 6-month survival rate after radiotherapy was 36% and the median survival period was 4.0 months. Ten patients had neurological improvement or pain relief after radiotherapy. Brain metastases were six fold more frequent in the patients with ISCM than in those with vertebral metastasis [89% vs. 15%, p = 0.001]. At the time of radiotherapy, back pain in patients with vertebral metastasis was more frequent [97% vs. 33%, p = 0.001] but neurological deficits were less common [24% vs. 100% , p = 0.001]. Most ISCM cases were diagnosed by contrast-enhanced MRI, with detection by contrast-enhanced CT in only 3/18 cases (17%). ISCM has a poor prognosis and most patients have neurological deficits that impair quality of life. Early diagnosis by MRI is important for suspected ISCM to allow initiation of radiotherapy before development of neurological deficits.

Background: Oblimersen, an ODN targeting BCL-2 RNA, has been shown to be effective in reducing BCL-2 expression in vitro and in in vivo models engineered to overexpress BCL-2. The present study evaluated the efficacy of combining BCL-2 ODN and radiation in small-cell lung cancers (SCLC) cell lines., Materials and Methods: The in vitro effect was determined using short term (cell viability) and long term (clonogenic) assays. Apoptosis, BCL-2 expression and intratumoural uptake of the FAM-ODN with or without prior radiation treatment were also evaluated. Combination of ODN and RT was also assessed in vivo., Results: Radiation was shown to increase intracellular and intratumoural penetration of oblimersen, confirming previous results obtained in prostate cancer xenograft models. Oblimersen decreased BCL-2 protein expression in vitro and in vivo. BCL-2 ODN sensitised H69 cells to radiation in vitro and in vivo. Oblimersen increased radiation-induced apoptosis and decreased in vivo tumoural vascularisation., Conclusion: Oblimersen was shown to increase in vitro and in vivo effect of RT on SCLC cell lines. Radiation increases intracellular and intratumoural penetration of ODN. This pre-clinical study argues in favour of clinical development in localised SCLC.

Context: The diagnosis of lung cancer is often confirmed by cytology and biopsy specimens obtained during a bronchoscopic procedure. At our institution, these specimens are read by different pathologists, and the rate of concordance was not known., Objectives: To evaluate the concordance rate in the diagnosis of lung cancer types between cytology and biopsy specimens and to correlate discordance with patient outcome., Design: Specimens obtained during the same procedure, between January 1, 2000, and December 31, 2005, were identified. Cases with cytology and biopsy specimens positive for cancer were evaluated for concordance of histologic type, small cell versus non–small cell lung carcinoma. Cases with different types were considered discordant, and slides were reviewed., Results: Of 231 cases, 225 (97.4%) had concordant diagnoses. Discordance was the result of misinterpretation of undifferentiated carcinoma, overinterpretation of squamous dysplasia, interpretation of suboptimal specimens with necrosis and crush artifact, and sampling error., Conclusions: Even though the cytology and biopsy specimens were reviewed by different pathologists, the concordance rate for histologic type at our institution was high, emphasizing that this is a safe practice. The few discordant cases did not affect the patient's outcome.

Brain FDG-PET after radiation therapy is classically used to differentiate between tumor recurrence and radiation-related tumor necrosis. Little is known about FDG-PET in patients with radiation-induced leukoencephalopathy without radiological aspect of necrosis. We present a 69-year-old woman who had preventive whole brain radiation after a diagnosis of paraneoplastic Lambert-Eaton syndrome related to small cell lung cancer Five months after radiation therapy, she developed radiation-induced leukoencephalopathy manifested by ataxia. Profound cerebellar hypometabolism on FDG-PET was in contrast with the presence of only discrete cerebellar white matter changes on MRI. FDG-PET abnormalities seem to correlate better with clinical signs related to radiation-associated brain toxicity than MRI.

Background and Purpose: The intervention rate (IR) of radiotherapy (RT) is important for health service planning. As actual IRs are commonly lower than those predicted by models, we sought to determine the reasons for this discrepancy, using lung cancer in a mixed urban-rural region of New Zealand (NZ)., Methods: The appropriate utilisation of RT was calculated as the sum of the actual utilisation 3 years post diagnosis (88% of cases deceased), the estimated utilisation of the 12% remaining alive, and the percentage of cases that may have benefited from RT but did not receive it., Results: The actual utilisation was estimated as 43% (range 40-48%). A further 8% of deceased cases may have benefitted from RT (but were not referred), giving an appropriate utilisation of 51%. An additional 3.5% that may have benefitted from RT declined management. The difference from modelled IRs was due to a combination of early mortality, refusal of treatment and assumed higher RT treatment rates for many clinical scenarios., Conclusion: The appropriate utilisation of RT was substantially lower than IRs derived from models. The assumptions from which these models were derived may result in over-estimates for resource planning purposes.

Background: The long-term benefits and risks of pneumonectomy after neoadjuvant chemoradiation therapy remain controversial. This study evaluated our experience with pneumonectomy for advanced non-small cell lung cancer (NSCLC) after concurrent chemoradiation therapy., Methods: We reviewed medical records from patients undergoing concurrent chemoradiation therapy, followed by pneumonectomy (1983 to 2007). Clinical variables affecting Kaplan-Meier survival were analyzed., Results: After chemoradiation therapy, 129 pneumonectomies (right, 65; left, 64) were performed. Postoperative pathologic stages were complete responders (CR), 21; I, 23; II, 19; III, 62; and IV, 4. The 90-day perioperative mortality was 20% (13 of 65) after right-sided pneumonectomy vs 9% (6 of 64) after left-sided pneumonectomy (p = 0.084). Complications occurred in 33% (43 of 129), including bronchopleural fistula in 12% (16 of 129) and acute respiratory distress syndrome in 2% (3 of 129). Overall 5-year survival was 33%. Survival was 32% for right-sided sections vs 34% for left-sided. CR patients had a 5-year survival of 48%. Survival of patients with postoperative N0, N1, and N2 nodes was 42%, 26%, and 28%, respectively. Multivariate analysis showed the development of major complications negatively affected 5-year survival for patients undergoing right-sided pneumonectomy (hazard ratio, 0.462; p = 0.0399)., Conclusions: Pneumonectomy after concurrent chemoradiation therapy achieved long-term survival. When neoadjuvant therapy resulted in complete response or nodal downstaging, survival was improved. The risk of early perioperative death and complications was higher for right-sided procedures, but long-term survival did not differ between right- and left-sided pneumonectomy. Major complications negatively affected 5-year survival with right-sided pneumonectomies.

Hypoxia-inducible factor-1 (HIF-1) has been suggested to play a major role in tumor radioresistance. However, the mechanisms through which irradiation regulates HIF-1alpha expression remain unclear. The purpose of this study was to investigate the mechanisms that mediate HIF-1 activation and thus radioresistance. Here, we show that irradiation induces survival and angiogenic activity in a subset of radioresistant lung cancer cell lines by elevating HIF-1alpha protein expression. Radiation induced HIF-1alpha protein expression mainly through two distinct pathways, including an increase in de novo protein synthesis via activation of phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) and stabilization of HIF-1alpha protein via augmenting the interaction between heat shock protein 90 (Hsp90) and HIF-1alpha protein. Whereas the PI3K/Akt/mTOR pathway was activated by irradiation in all the lung cancer cells examined, the Hsp90-HIF-1alpha interaction was enhanced in the resistant cells only. Inhibition of Hsp90 function by 17-allylamino-17-demethoxygeldanamycin or deguelin, a novel natural inhibitor of Hsp90, suppressed increases in HIF-1alpha/Hsp90 interaction and HIF-1alpha expression in radioresistant cells. Furthermore, combined treatment of radiation with deguelin significantly decreased the survival and angiogenic potential of radioresistant lung cancer cells in vitro. We finally determined in vivo that systemic administration of deguelin resulted in profound inhibition of tumor growth and angiogenesis when combined with radiation. These results provide a strong rationale to target Hsp90 as a means to block radiation-induced HIF-1alpha and thus to circumvent radioresistance in lung cancer cells.

Background: Patients with stage III non-small-cell lung cancer (NSCLC) and limited disease small-cell lung cancer are excluded from concurrent chemoradiation mostly on the basis of comorbidity and age. The purpose of this prospective study was to get insight in what proportion of patients with locally advanced lung cancer would be suitable for concurrent chemoradiation., Patients and Methods: From 2002 to 2005, all patients with a pathological diagnosis of lung cancer and with locally advanced disease in the Maastricht Cancer Registry, the Netherlands, comorbidity were prospectively assessed. Patients were regarded as noneligible for concurrent chemoradiation if they had one or more important comorbidity or were 75 years or older., Results: In all, 711 patients were included, 577 with NSCLC and 134 with SCLC. Overall, 166 patients (23.3%) were 75 years or older. Of the 526 patients <75 years, comorbidities were as follows: 278 (52.9%) 0, 188 (35.7%) 1, and 56 (11.4%) 2 or more. In all, 408/686 (59%) of the whole patient group were considered as ineligible for concurrent chemoradiation., Conclusions: More than half of patients with stage III lung cancer were theoretically not eligible for concurrent chemoradiation. Less toxic alternatives are needed for these patients.

Background: The purpose of this study was to determine in limited small-cell lung cancer if locoregional irradiation concurrently with induction chemotherapy with cisplatin and etoposide prolongs survival when cisplatin is given daily as a radiosensitiser., Patients and Methods: Two-hundred and four eligible patients were randomised between standard radiosensitised induction chemoradiotherapy (arm A) with cisplatin (90 mg/m(2) day 1) plus etoposide and daily radiosensitised induction chemoradiotherapy (arm B) with cisplatin (6 mg/m(2)/day) plus etoposide. Chemotherapy and chest irradiation (39.90 Gy in 15 fractions >3 weeks) both started on day 1., Results: There was no difference in survival between both arms with respective median, 2 and 5 years of 15.5 months, 35% and 18% in arm A and 17.0 months, 38% and 21% in arm B (P = 0.50). Performance status and T status were identified as independent prognostic factors for survival. In terms of local control rate, there was a statistical trend in favour of arm A with 2% only local relapse versus 10% in arm B. Daily cisplatin radiosensitisation was associated with more oesophagitis and thrombopenia but less nephrotoxicity., Conclusion: Induction chemoradiotherapy resulted in both arms in good long-term survival, comparable to the best reported results and without improvement by daily cisplatin administration.

The usefulness of serum pro-gastrin-releasing peptide (ProGRP) as a tumor marker in patients with small cell lung cancer has recently drawn the attention of many research centers. The aim of the study was the evaluation of ProGRP, neuron-specific enolase (NSE), soluble fragment of cytokeratin 19 (CYFRA 21-1) and lactate dehydrogenase (LDH) levels at the time of diagnosis and during chemo- and radiotherapy of small cell lung cancer patients with limited disease (SCLC-LD). The studies were performed on a group of 64 patients with SCLC-LD who had received no prior therapy. All the patients were given the same treatment regimen. ProGRP, NSE, CYFRA 21-1 and LDH were measured before each course of chemotherapy and then at 3 and 6 months after the end of treatment. Prior to therapy, elevated levels of ProGRP, NSE, CYFRA 21-1 and LDH were found in 79.7%, 57.8%, 23.4%, and 12.5% of the patients respectively. Before the second chemotherapy course, all the tumor marker levels except LDH decreased significantly in comparison with the pretreatment concentrations. However, only ProGRP levels showed a progressive drop during consecutive courses of therapy, while NSE and CYFRA 21-1 fluctuated within reference ranges. When the study group was divided with respect to the effect of treatment evaluated six months from its termination, significant differences in ProGRP levels were found between both subgroups throughout all therapy and follow-up, except for the fifth course of chemotherapy. Differences in NSE levels were only significant for the first two courses and follow-up. Univariate analysis showed significant relationships between disease-free survival and the initial levels of NSE and CYFRA 21-1 as well as between overall survival and prophylactic cranial irradiation (PCI) and the initial ProGRP, NSE and CYFRA 21-1 levels. Changes of ProGRP level seem to be more precise than NSE as a tool for monitoring therapy in SCLC patients with limited disease, but for prediction of relapse, in addition to NSE determinations of ProGRP seem to be optimal.

Background: The indications for definitive thoracic radiotherapy (TRT) in limited-disease small cell lung cancer (LD-SCLC) and ipsilateral pleural effusion have not been thoroughly investigated. We retrospectively investigated the clinical outcome of LD-SCLC patients with ipsilateral pleural effusion., Methods: The medical records of SCLC patients who received treatment at the National Cancer Center Hospital East between July 1992 and December 2006 were reviewed. Sixty-three of the 373 LD-SCLC patients (17%) had ipsilateral pleural effusion. Of these, 62 patients received chemotherapy as an initial treatment, and were included in this study. Since about 1998, definitive TRT was routinely performed if the patient's pleural effusion disappeared after induction chemotherapy. The 62 patients were divided into three subgroups: group A included patients who received chemotherapy and TRT (n = 26), group B included patients who did not receive TRT in spite of the disappearance of pleural effusion after first-line chemotherapy (n = 8), and group C included patients who did not receive TRT and whose pleural effusion persisted after first-line chemotherapy (n = 28)., Results: The response rate for first-line chemotherapy was 74%. Ipsilateral pleural effusion disappeared after first-line chemotherapy in 34 patients (55%). The median overall survival time was 11.8 months, and the 2 and 3-year survival rates were 21 and 10%, respectively. In groups A, B, and C, the median survival times were 19.2, 10.5, and 9.2 months, respectively, and the 2-year survival rates were 38, 25, and 7%, respectively., Conclusion: Long-term survival was achieved by LD-SCLC patients with ipsilateral pleural effusion who successfully underwent chemoradiotherapy.

Paraneoplastic optic neuropathy (PON) is a rare syndrome usually associated with small cell lung carcinoma. In the 27 rigorously reported cases, neurologic manifestations other than visual loss have been present in all but 2. In the single case in which vision improved in response to treatment of the cancer, the collapsin response-mediating protein (CRMP)-5 titer did not change, and the ophthalmic examination was not detailed. We describe a patient with optic neuropathy and vitritis as the only clinical manifestations of PON marked by an extremely high titer of CRMP-5 antibody. Treatment of the underlying small cell lung cancer coincided with resolution of the visual abnormalities and a dramatic decrease in the CRMP-5 titer.

Background and Purpose: Diffusion tensor imaging (DTI) will show abnormal fractional anisotropy (FA) in the normal-appearing brain after prophylactic cranial irradiation (PCI). These abnormalities will be more accentuated in patients with underlying vascular risk factors., Materials and Methods: A prospective study by use of DTI and conventional T2-weighted MR images was performed with a 1.5T unit with 16 patients with small cell lung cancer and undergoing PCI. All of the T2-weighted images were evaluated with respect to abnormalities in signal intensity of white matter as markers of radiation damage. Measurements of FA were performed before, at the end of, and 6 weeks after radiation therapy. On the FA maps, the bifrontal white matter, the corona radiata, the cerebellum, and the brain stem were evaluated. FA values were compared with respect to age, demographic, and vascular risk factors. Statistical analyses (Friedman test, Wilcoxon test, and Mann-Whitney U test) were performed., Results: Fractional anisotropy decreased significantly in supratentorial and infratentorial normal-appearing white matter from the beginning to the end of PCI (P < .01). A further decline in FA occurred 6 weeks after irradiation (P < .05). A stronger reduction in FA was observed in patients with more than 1 vascular risk factor. There was an age-related reduction of white matter FA. Patients 65 years and older showed a trend toward a stronger reduction in FA., Conclusion: During the acute phase, after PCI, patients with many vascular risk factors showed stronger damage in the white matter compared with patients with only 1 risk factor.

Small cell carcinoma of the bile duct system is extremely rare, and surgical procedures have been complicated by early hematogenous dissemination. In this study, we report a patient with small cell carcinoma of the bile duct system presenting with jaundice. The diagnosis was made early by endoscopic ultrasonography-guided fine needle aspiration biopsy (EUS-FNA). We performed radiation therapy of a total of 30 Gy, resulting in a marked decrease of serum neuron specific enolase levels and amelioration of jaundice, which had been resistant to drainage procedures. The patient was then treated with combined chemotherapy of cisplatin and CPT-11, which resulted in the disappearance of the tumor mass by image tests.

The UK has been reported to have the lowest resection and survival rates for lung cancer patients. These reports were based largely on retrospective data from the cancer registry and are now outdated. To monitor the present day surgical resection rate at our institution all newly diagnosed cases of lung cancer presenting to us were enrolled into a prospective tracking study. From September 2003 to March 2005 all suspected primary lung cancer referrals to the North West Lung Centre were tracked to identify patients with newly diagnosed lung cancer. The histology of 247 patients confirmed to be new lung cancer cases were small cell (SCLC), non-small cell (NSCLC) and mixed cancers in 33 (16%), 170 (83.5%) and 1 (0.5%) patients, respectively, while 43 patients had no histological confirmation. Overall, 43 patients (17%) underwent surgery while chemotherapy and radiotherapy were used in 91 (38%) and 43 (17%), respectively. Out of 170 confirmed NSCLC patients, 43 (25%), 65 (38%) and 27 (16%) patients underwent surgery, chemotherapy and radiotherapy, respectively. The remaining 35 (20%) did not receive any treatment because of patient wishes or poor condition. The surgical resection rates were 17% for all lung cancers and 25% for NSCLC. Current surgical resection rates at the South Manchester University Hospital are comparable to international standards. Similar data from the rest of the UK are required to determine the national resection rate, which may not be as low as once thought to be.

Background and Aim: Out-patient high-dose-rate endobronchial brachytherapy (HDREB) is a possible option in the palliation of symptoms in patients with advanced lung cancer, but literature data is limited and the technique is still under development in Italy. Our aim was to evaluate safety and effectiveness of out-patient HDREB for palliation of malignant endobronchial tumours in the context of a multidisciplinary approach., Methods: Out-patient HDREB sessions were scheduled at weekly intervals (500-1000 cGy per session) with prior Diodi-laser resection in some cases. Response was assessed bronchoscopically, clinically and functionally at the end of treatment and one month after the last HDREB session. Inclusion criteria was: histological evidence of malignant tumour not susceptible to surgical treatment for extension or co-morbidity., Results: 150 outpatient HDREB sessions were carried out on consecutive 35 patients (mean age 69 yrs, M/F 29/6) with symptoms due to central airway obstruction. A shortterm endoscopic response was observed in 15/28 patients. After delivering 2000 cGy dyspnoea decreased significantly. After one month cough decreased and haemoptysis disappeared. Palliation was obtained in all patients except one during. Lung function tests did not significantly improve after HDREB. No fatal complication occurred. A temporary radiation bronchitis was observed in six patients., Conclusions: This non-comparative, prospective observational study showed a palliative response of HDREB in most of patients with advanced endoluminal lung cancer. The safety of the procedure was good and the rate of non-fatal serious complications was very low.

Purpose: We sought to evaluate the activity and tolerance of the rationally designed sequence of paclitaxel-topotecan-etoposide, a nonplatinum regimen, as induction therapy for limited-stage small-cell lung cancer before combined chemo- and radiotherapy., Patients and Methods: Patients with measurable disease, performance status 0 to 2, no prior therapy, and adequate organ function were eligible. Paclitaxel (110 mg/m2, administered intravenously on day 1), topotecan (1.5 mg/m2, administered orally on days 2 to 4), and etoposide (160 mg/m2, administered orally on days 5 to 7 every 21 days), with filgrastim for two cycles, were followed by chest irradiation to 70 Gy (to postinduction tumor volume) concurrent with carboplatin (area under the curve of 5, administered intravenously on day 1) and etoposide (100 mg/m2 on days 1 to 3 every 21 days) without filgrastim for three cycles (five chemotherapy cycles total). We aimed to determine the response rates to induction and overall therapy, overall and failure-free survival, and toxicity. The primary statistical endpoint was to differentiate between complete response rates of 50 and 70% for the overall treatment program., Results: Between June 2001 and January 2003, 65 patients were enrolled, but one never started therapy, and one was ineligible. Patient characteristics included male/female, 27/36; white/black/other/unknown, 58/3/1/1; median age 62 (range, 38-78); performance status 0/1/2, 27/33/3. Induction chemotherapy resulted in six (10%) complete responses and 35 (56%) partial responses. Overall response to chemoradiotherapy included 27 (43%; 95% confidence interval [CI] 30-56%) complete responses and 24 (38%) partial responses. Median progression-free survival is 12 months (95% CI, 9-15 months). Median overall survival is 20 months (95% CI, 16-24 months). Frequent (>20%) grade 3/4 toxicities during all therapy included neutropenia, febrile neutropenia, anemia, thrombocytopenia, fatigue, and dysphagia. One patient died of febrile neutropenia, one died of febrile neutropenia and typhlitis, and one patient who declined transfusion for anemia died of cardiac ischemia., Conclusions: This treatment regimen has significant activity in limited-stage small-cell lung cancer but did not meet our prospectively defined criteria for further investigation in this setting. The addition of etoposide and the use of a sequenced administration schedule did not seem to improve overall activity beyond our prior experience with a topotecan-paclitaxel doublet.

Introduction: The optimal initial radiotherapy utilization rate for lung cancer is estimated to be 76% of all new cases. The actual re-treatment rate has not been defined. Re-treatment information can aid clinical decision making and resource planning. The aim of this study was to examine the indications for re-treatment in a population cohort and report the proportion of patients who receive more than one radiotherapy treatment for lung cancer throughout their lifetime., Methods: A retrospective longitudinal analysis of a cohort of patients with lung cancer treated with radiotherapy in the South Western Sydney Area Health Services (SWSAHS) in 1993 and 1996 was performed. The indication for and timing of all episodes of radiotherapy were recorded and analyzed using SPSS Data 3.5 software (SPSS, Inc., Chicago, IL)., Results: Of the 527 patients diagnosed with lung cancer in the study period, 279(53%) were treated at least once with radiotherapy. Initial radiotherapy was palliative for 79%, definitive for 14%, and adjuvant for 7%. The most common sites of initial radiotherapy were chest (79%), bone (10%), and brain (9%). Of the 279 patients, 73 (27%) received treatment with a second course of radiotherapy, 19 (7%) had a third radiotherapy episode, and 6 (2%) had a fourth. One patient had five radiotherapy episodes. Overall, there were 328 radiotherapy courses delivered to the 279 patients., Discussion: The re-treatment rate for our cohort was 27%, exceeding other estimations of re-treatment. Common sites re-treated were chest and bone. Re-treatment was 17% of the initial linear accelerator treatment delivery work load for lung cancer.

Introduction: Evidence that has been published in the last decade indicates that in patients with limited-stage small-cell lung cancer (SCLC), hyperfractionated accelerated thoracic radiotherapy (RT) given twice daily and prophylactic cranial irradiation (PCI) have each separately improved survival. Concerns about the toxicities associated with these treatments and uncertainty about their impact on survival outside the trial setting may have restricted the extent to which they have been incorporated into standard treatment protocols. We have reviewed the experience at Peter MacCallum Cancer Centre to determine the tolerability of these treatments in routine practice and to determine their effects on survival., Methods: A retrospective review of patients with limited-stage SCLC receiving a radical course of thoracic RT between June 1998 and May 2002, including either conventional fractionation at 50 Gy for 5 weeks, or hyperfractionated accelerated RT at 45 Gy for 3 weeks. Patients achieving a complete response were offered PCI at 36 Gy in 18 fractions. The main outcomes recorded were RT toxicity (graded using CTCAE v. 3.0 and RTOG/EORTC late scoring criteria), response, relapse-free survival, and overall survival., Results: Ninety patients were identified as having undergone radical-intent thoracic RT, with a median potential follow-up of 4.2 years. Fifty-seven patients (63%) were treated with hyperfractionated accelerated RT, and 33 (37%) were treated with conventional fractionation. Forty-six patients (51%) received PCI. Patients receiving hyperfractionated accelerated RT compared with conventional fractionation had higher rates of grade 3 and 4 esophagitis (14% versus 6%; p = 0.312), a higher rate of treatment interruptions (12% versus 3%; p = 0.250), and a higher hospital admission rate (39% versus 15%; p = 0.031). The majority of patients were able to complete the planned treatment, and there were no treatment-related deaths. Median survival for all patients from commencement of RT was 14.2 months (95% confidence interval [CI]: 11.9-18.1 months), and survival at 2 years was 24.8% (95% CI: 16.9-35.0%). On multifactor analysis, the only factor associated with longer survival was PCI (hazard ratio = 0.40; p < 0.001)., Conclusions: Hyperfractionated accelerated RT was more toxic than conventional fractionation, but it was possible to deliver treatment as planned in the majority of patients. PCI was associated with improved survival. Both treatments can be incorporated into routine practice.

Background: Acute dysphagia is a distressing dose-limiting toxicity after concurrent chemoradiation or high-dose radiotherapy for lung cancer. We therefore identified factors associated with the occurrence of acute dysphagia in lung cancer patients receiving radiotherapy alone or combined with chemotherapy., Patients and Methods: Radiotherapy, chemotherapy and patient characteristics were analyzed using ordinal regression analysis as possible predictors for acute dysphagia (CTCAE 3.0) in 328 lung cancer patients treated with curative intent., Results: The most significant association was seen between the maximal grade of neutropenia during chemoradiation and dysphagia, with an odds ratio increasing from 1.49 [95% confidence interval (CI) 0.63-3.54, P = 0.362] for grade 1-2 neutropenia to 19.7 (95% CI 4.66-83.52, P < 0.001) for patients with grade 4 neutropenia. Twice-daily schedule, mean esophageal dose and administration of chemotherapy were significant predictive factors. By combining these factors, a high-performance predictive model was made. On an individual patient level, 64% of patients were correctly classified and only 1.2% of patients were misclassified by more than one grade., Conclusions: The maximal neutrophil toxicity during concurrent chemotherapy and radiotherapy is strongly associated with the development of acute dysphagia. A multivariate predictive model was developed.

We describe our experience of treatment for a giant esophageal malignant fistula, which has not been reported previously. A 36-year-old woman who was diagnosed as having massive esophageal small cell carcinoma with metastases was treated with chemoradiotherapy. However, a giant esophagomediastinal fistula appeared due to shrinkage of the massive tumor, and all anti-cancer treatment was suspended. However, chemoradiotherapy was restarted at the request of the patient despite the presence of the fistula. After restarting treatment, the giant esophageal fistula was naturally closed despite intensive chemoradiotherapy, and the patient became able to eat and drink. Although the patient finally died, her QOL and prognosis seemed to be improved by the chemoradiotherapy. Anti-cancer treatment could be safely performed despite the presence of a giant fistula. The giant fistula closed while intensive chemotherapy was administered to the patient. Therefore, the presence of a fistula may not be a contraindication for curative chemoradiotherapy. Completion of treatment with proper management and maintenance of patients would be of benefit to patients with fistula.

Background: We report on a rare case of small cell cancer located at the anal canal., Case Report: A 41-year old woman presented with locally advanced small cell anal cancer and simultaneous hepatic and pulmonal deposits. Due to metastatic disease, chemotherapy with etoposide and cisplatin was performed with mixed response after four cycles of chemotherapy. After application of two additional chemotherapy cycles, locally progressive disease occurred causing symptomatic bowel obstruction. Pelvic irradiation was started and, several days later, additional irradiation of cerebral metastases was initiated due to rapid progression of distant disease. Despite adequate local treatment the patient's condition further deteriorated and irradiation was stopped. The patient died 10 months after initial diagnosis due to rapid tumor progression., Conclusion: In patients with metastatic small cell anal cancer chemotherapy remains the mainstay of therapy. Radiotherapy exerts additional activity and remains a prime choice to gain local control and ameliorate symptoms. Careful histopathological examination, together with immunohistochemistry, is needed to determine the therapeutic strategy to be followed.

Introduction: The real benefit of surgical treatment of small cell lung cancer (SCLC) has never been demonstrated, mainly because of the rarity of surgical cases and the difficulty in comparing surgical and medical series for the different classifications systems used by surgeons (tumor, node, metastasis) and medical oncologists and radiotherapists (Veterans Administrations Lung Cancer Study Group)., Materials and Methods: We prospectively assessed the utility of surgery after chemotherapy (carboplatin plus VP16 with or without ifosfamide) with or without radiotherapy in 23 patients with preoperative diagnosis of resectable stage I to IIIA SCLC. A median of three (range: three to six) courses of chemotherapy were administered. Five pneumonectomies, 12 lobectomies (seven sleeve resections), and two segmentectomies were performed, and all except one received radical lymph node dissection. Four (17%) patients received exploratory thoracotomy. Nine (39%) patients received postoperative thoracic radiotherapy., Results: Pathological stages were complete response in four patients, stage I in seven patients, stage II in seven patients, and stage III in five patients. Thirty-day morbidity and mortality were 9% and 0%, respectively. Surgery-related mortality at 90 days was 9%. Median follow-up was 19 months. Overall and local relapse rates were 52% and 17%, respectively. Median overall and disease-free survival were 24 and 12 months. Patients with complete response or pathological stage I had a significantly better Kaplan-Meier survival and lower incidence of relapse than those with more advanced pathological stage (p = 0.025 and 0.027, respectively, log rank)., Conclusions: Survival after chemotherapy and surgery in the series correlated with pathological but not pretreatment stage. Only patients with pathological stage 0 or I disease seem to benefit from surgical resection.