Second hand smoke exposure and survival in early-stage non-small-cell lung cancer patients.

PURPOSE: Second hand smoke (SHS) exposure is associated with higher risk of lung cancer. However, the role of SHS in lung cancer survival is not clear. EXPERIMENTAL DESIGN: We examined the association between self-reported SHS exposure before diagnosis and overall survival and recurrence-free survival in 393 early-stage non-small-cell lung cancer patients. SHS exposure was analyzed by both duration and location of exposure using log-rank test and Cox proportional hazard models, adjusting for covariates including pack-years of smoking. RESULTS: The median follow-up time was 66 months (range, 0.2-140 months). There were 135 recurrences and 213 deaths. The 5-year overall survival rates were 71% [95% confidence interval (95% CI), 62-81%], 61% (51-72%), 49% (38-60%), and 47% (37-58%), respectively, for patients with the lowest to highest quartile of SHS exposure durations (P < 0.001, log-rank test), with the adjusted hazard ratio (AHR) of 1.57 (95% CI, 1.02-2.41) for the highest versus lowest quartile of SHS exposure durations (P(trend) = 0.04). For different SHS exposure locations, a stronger association was found for SHS exposure at work (AHR of the highest versus lowest quartile, 1.71; 95% CI, 1.12-2.61; P(trend) = 0.03) than for exposure at home (AHR, 1.26; 95% CI, 0.86-1.86; P(trend) = 0.20) or leisure places (AHR, 1.28; 95% CI, 0.83-1.95; P(trend) = 0.16). Similar associations were observed when SHS exposure durations were dichotomized into two or three groups and between SHS exposure and recurrence-free survival. CONCLUSIONS: SHS exposure is associated with worse survival in early-stage non-small-cell lung cancer patients, especially for SHS exposure at the work.     

Is there a difference in outcome between stage I-II endometrial cancer of papillary serous/clear cell and endometrioid FIGO Grade 3 cancer?

PURPOSE: Several reports in the literature have shown that, compared with endometrioid adenocarcinoma, patients with papillary serous (PS) and clear cell (CC) histologic features do worse. However, it is unclear whether the outcome of PS/CC cancer is different from that of poorly differentiated endometrioid cancer. The purpose of this study was to compare the outcome between PS/CC and endometrioid International Federation of Gynecology and Obstetrics (FIGO) Grade 3 cancer and was limited to patients with Stage I-II uterine carcinoma. METHODS AND MATERIALS: Between November 1987 and September 1999, 83 patients with Stage I endometrial cancer and Stage II occult endometrial cancer were treated with simple hysterectomy and high-dose-rate intravaginal brachytherapy. Forty-one patients (49%) had FIGO Grade 3 endometrioid tumors (Group 1) and 42 (51%) had PS/CC histologic features (Group 2). The mean age was 63 years (range 30-89). Comprehensive surgical staging was done in 23 (28%) of 83 patients. Capillary space-like invasion (CSLI) was seen in 24 (29%) of 83 patients. The median dose of intravaginal brachytherapy when used alone was 21 Gy in 3 fractions. Additional external beam radiotherapy was given to 42 (51%) of 83 patients to 45 Gy. The two groups were balanced with regard to age, race, comprehensive surgical staging, amount of myometrial involvement, CSLI, lower uterine segment involvement, cervical involvement, and use of external beam radiotherapy. The median follow-up was 46 months (range 4-147). RESULTS: The pattern of relapse was as follows: vagina/pelvis in 5 of 14 patients, lungs in 8 of 15, intra-abdominal in 4 of 12, and supraclavicular lymph nodes in 1 of 14. One of the four intra-abdominal disseminations was in Group 1 and the other three in Group 2 (p = 0.6). The 5-year vaginal/pelvic control, disease-free survival (DFS), and overall survival (OS) rate was 93% (95% confidence interval [CI] 87-99%), 79% (95% CI 69-89%), and 74% (95% CI 64-85%), respectively. No significant difference in outcome was found between Groups 1 and 2. The 5-year vaginal/pelvic control rate was 97% (95% CI 91-100%) in Group 1 compared with 90% (95% CI 81-99%) in Group 2 (p = 0.2). The 5-year DFS rate was 79% (95% CI 64-95%) in Group 1 vs. 78% (95% CI 65-92%) in Group 2 (p = 0.6), and the 5-year OS rate was 71% (95% CI 55-87%) in Group 1 vs. 79% (95% CI 66-92%) in Group 2 (p = 0.3). The influence on outcome of age, race, comprehensive surgical staging, CSLI, amount of myometrial invasion, cervical involvement, lower uterine segment involvement, and presence of pure PS or CC histologic features was evaluated. On multivariate analysis, only CSLI correlated with poor DFS (p = 0.04; relative risk 3, 95% CI 1-9) and OS (p = 0.02; relative risk 3, 95% CI 1-6). CONCLUSION: On the basis of the results of this study, no significant difference in outcome exists between patients with Stage I-II endometrial cancer with PS/CC histologic features and those with similar stage disease, but with FIGO Grade 3 endometrioid histologic features. CSLI was the only independent predictor of poor DFS and OS.     

Lung Cancer Survival with Current Therapies and New Targeted Treatments: A Comprehensive Update from the Srinagarind Hospital-Based Cancer Registry from (2013 to 2017)

Background: Lung cancer (LC) is a common malignancy and leading cause of cancer death worldwide and in Thailand. An update on LC survival factors after diagnosis at Srinagarind Hospital is needed. Methods: We conducted a retrospective cohort study, and the data were sourced from the Srinagarind Hospital-Based Cancer Registry. All LC cases were diagnosed between January 1, 2013, and December 31, 2017, and followed up until November 30, 2019. Cases of LC (ICD-O-3) numbered 2,149, but only those with coding C34.0-C34.9 were included. The survival rate was estimated using Kaplan-Meier, while the Log-rank test was used to estimate survival. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard regression models. Results: The 2,149 patients had a total follow-up of 269.6 person-years. Overall, 1,867 patients died during the study, for a corresponding case-fatality mortality rate of 86.0 per 100 person-years. The respective 1-, 3-, and 5-year survival rate was 31.2 % (95% CI; 29.21 to 33.15%), 12.9 % (95%CI: 11.49 to 14.45), and 10.2% (95%CI: 8.74 to 11.70). After patient diagnosis, the median survival time was 0.46 years (5.51 months) (95% CI: 0.42 to 0.50). Targeted therapy was associated with longer survival than non-targeted therapy (p-value < 0.001). After adjusting for sex, TNM stage, and histologic type, multivariable analysis of the entire cohort identified chemotherapy as an independent predictor of improved survival (adjusted HR= 0.48; 95% CI: 0.42 to 0.55; P < 0.001), and that sex, TNM stage, and histologic type were associated with survival. Conclusion: The study confirmed that sex, stage of disease, histology, and chemotherapy are associated with survival of LC. Primary prevention and screening for early detection improve survival. Further investigations into factors affecting survival of LC in Northeast Thailand should focus on targeted therapy.     

Effect of platinum combined with irinotecan or paclitaxel against large cell neuroendocrine carcinoma of the lung

BACKGROUND: The efficacy of chemotherapy in patients with large cell neuroendocrine carcinoma of the lung (LCNEC) remains unclear. METHODS: Of 42 consecutive patients with LCNEC, 22 with measurable disease receiving chemotherapy were enrolled as the subjects of this study. The clinical characteristics and objective responses to chemotherapy in these patients were analysed retrospectively. RESULTS: The distribution of the disease stage in the patients consisting of 21 males and one female (median age: 67 years; range: 47-78 years) was as follows: stage IIB (n = 1), stage IIIA (n = 1), stage IIIB (n = 5), stage IV (n = 8), and post-operative recurrence (n = 7). Chemotherapy consisted of cisplatin and irinotecan (n = 9), a platinum agent and paclitaxel (n = 6), paclitaxel alone (n = 1), cisplatin and vinorelbine (n = 1), cisplatin and docetaxel (n = 1), and a platinum and etoposide (n = 4). The objective response rate in the 22 patients was 59.1% (95% CI, 38.1-80.1). An objective response was obtained in five of the nine patients receiving irinotecan and five of the seven patients receiving paclitaxel. The progression-free survival, median overall survival and 1-year survival rates were 4.1 months (95% CI, 3.1-5.1), 10.3 months (95% CI, 5.8-14.8) and 43.0% (95% CI, 20.7-65.3), respectively. The median overall survival of the patients treated with irinotecan or paclitaxel was 10.3 months (95% CI, 0-21.8), and the 1-year survival rate of these patients was 47.6% (95% CI, 20.4-74.8). CONCLUSION: Our results suggest that irinotecan and paclitaxel may be active against LCNEC.     

Epidemiology and Survival of Hepatocellular Carcinoma in North-east Peninsular Malaysia

The incidence of hepatocellular carcinoma (HCC) is relatively high in Southeast Asia. Globally, HCC hasa high fatality rate and short survival. The objectives of this retrospective cohort study were to review theepidemiology and survival of HCC patients at a tertiary centre in north-east of Peninsular Malaysia. Subjectswere adult HCC patients diagnosed by histopathology or radio-imaging. Secondary liver carcinoma was excluded.Kaplan Meier and multiple Cox proportional hazard survival analyses were used. Only 210 HCC cases fromyears 1987-2008, were included in the final analysis. The number of cases was increasing annually. The mean agewas 55.0 (SD 13.9) years with male:female ratio of 3.7:1. Approximately 57.6% had positive hepatitis B virus,2.4% hepatitis C virus, 20% liver cirrhosis and 8.1% chronic liver disease. Only 2.9% had family history and9.0% had frequently consumed alcohol. Most patients presented with abdominal pain or discomfort and hadhepatomegaly, 47.9% had an elevated α-fetoprotein level of 800 IU/ml or more, 51.9% had multiple tumors and44.8% involved multiple liver lobes. Approximately 63.3% were in stage 3 and 23.4% in stage 4, and 82.9%did not receive any treatment. The overall median survival time was 1.9 months (95% confidence interval(CI): 1.5, 2.3). The 1-month, 6-month, 1-year and 2-year survival rates were 71.8%, 23.3%, 13.0% and 7.3%respectively. Significant prognostic factors were Malay ethnicity [Adjusted hazard ratio (AHR) 1.6; 95%CI: 1.0,2.5; p=0.030], no chemotherapy [AHR 1.7; 95%CI: 1.1, 2.5; p=0.017] and Child-Pugh class C [AHR 2.6; 95%CI:1.4, 4.9; p=0.002]. HCC in our study affected a wide age range, mostly male, in advanced stage of disease, withno treatment and very low survival rates. Primary prevention should be advocated in view of late presentationand difficulty of treatment. Vaccination of hepatitis virus and avoidance of liver toxins are to be encouraged.     

Outcomes of Treatment,Survival Rates,and Factors related to Survival of Stage III Lung Cancer Patients Treated at Srinagarind Hospital,Faculty of Medicine,Khon Kaen University,Thailand

Background: Lung cancer (LC) is the leading cause of death worldwide. Stage III lung cancer (Stage III-LC) is characterized by local metastasis. The treatments for LC differ at each stage, while for stage IIIA and IIIB treatment various approaches have been tried with uncertain results. We determined the survival time of Stage III-LC patient and compared survival among multiple factors. Methods: Data were collected from the Srinagarind Hospital-Based Cancer Registry (2014 - 2019). 324 patients from Srinagarind Hospital, Faculty of Medicine, Khon Kaen University, Thailand, were followed up until December 31, 2021. The survival rate was estimated using Kaplan-Meier and the Log-rank test. In addition, hazard ratios (HR) and the 95% CI were estimated using Cox regression. Results: Of the 324 Stage III-LC patients, the total follow-up time was 447.3 person-years, and 288 cases died during the study, for a mortality rate of 64.4 per 100 person-years (95% CI: 57.40-72.27). The respective 1-, 3-, and 5-year survival rate was 44.1% (95% CI: 38.67-49.45), 16.2 (95% CI: 12.34-20.51), and 9.3 (95% CI: 6.14-13.31). The median survival time was 0.84 years (10.1 months) (95% CI: 0.73-1.00). After adjusting for sex and stage of disease, sequential chemoradiotherapy (SC) represented the most independent predictor of the risk of death (adjusted HR= 1.58; 95% CI: 1.41-2.18). Females had a mortality risk of 0.74-fold compared to males (adjusted HR = 0.74, 95% CI: 0.57-0.95). Stage of disease and stages IIIB and III (unknown and undefined) had a respective 1.33-fold (adjusted HR = 1.33, 95% CI: 1.00-1.84) and 1.48-fold (adjusted HR = 1.48, 95% CI: 1.09-2.00) risk of death compared to stage IIIA. Conclusion: Sex, stage of disease, and SC were related to stage III-LC survival, so physicians should emphasize combination therapy. Further research should focus on combination therapy and survival among Stage III-LC patients.     

Health Insurance and Colorectal Cancer Survival in Khon Kaen,Thailand

Background: Evidence from healthcare studies demonstrates that patients’ health insurance affects serviceaccessibility and the outcome of treatment. However, assessment on how colorectal cancer survival relates to healthinsurance is limited. Objective: The study examined the association between health insurance and colorectal cancersurvival in Khon Kaen, Thailand. Methods: The retrospective cohort study was conducted with 1,931 colorectal cancerpatients from Khon Kaen cancer registry between January 1, 2003 and December 31, 2012, and was followed-up untilDecember 31, 2015. Relative survival was used to estimate the survival rate. Cox proportional hazard regression wasused to estimate the relationship between health insurance and colorectal cancer survival, represented with the hazardratio. Result: Most of the participants were males, and the median age was 62 years. The median survival time was2.25 years (95% CI: 2.00-2.51). The five-year observed survival rate and relative survival rate were 36.87 (95% CI:34.66-39.08) and, 42.28 (95% CI: 39.75-44.81), respectively. The factors that showed significant associations withpoorer survival after adjustment for gender and age were non-surgical treatments (HRadj=1.88;95%CI=1.45-2.45),advanced stage (III+IV) (HRadj=2.50; 95%CI=2.00-3.12), histological grading in poorly differentiated (HRadj=1.84;95%CI=1.32-2.56), and Universal Coverage Scheme (HRadj=1.37;95%CI=1.09-1.72). Conclusion: The survival ofcolorectal cancer patients in the Universal Coverage Scheme was likely to be poorer than in the Civil Servant MedicalBenefit Scheme. This indicates an urgent need for a national program for colorectal cancer screening in the generalpopulation and access to health insurance.     

Late mortality from pT1N0M0 breast carcinoma.

BACKGROUND: pT1N0M0 breast carcinoma (< or = 2 cm in greatest dimension, lymph node negative) is associated with generally favorable 5-year and 10-year survival, but to the authors' knowledge there are few data available regarding the long term outcome of these patients. METHODS: The authors identified women with breast carcinoma diagnosed between 1945-1984 in a geographically defined urban population using the files of the Finnish Cancer Registry and local hospital records (n = 1495). The clinical and autopsy records and histologic slides were reviewed. The series contained 265 patients with unilateral pT1N0M0 breast carcinoma treated with mastectomy and axillary lymph node dissection without adjuvant systemic therapy and who were followed for 10-44 years (median, 17 years) after the initial diagnosis or until death. RESULTS: The last death from pT1N0M0 breast carcinoma occurred 23 years after the initial diagnosis. The 20-year overall survival rate was 54% (95% confidence interval [95% CI], 48-60%) and the survival rate when corrected for intercurrent deaths was 81% (95% CI, 75-87%). The 20-year survival rate when corrected for intercurrent deaths was 92% (95% CI, 86-98%) in patients with T1a-b disease (primary tumor < or = 10 mm), but was only 75% (95% CI, 64-86%) in patients with pTc disease (range, 11-20 mm). None of the patients with well differentiated (World Health Organization Grade 1) pTa-b tumors died of breast carcinoma (n = 48) whereas the 20-year survival rate when corrected for intercurrent deaths was 81% (95% CI, 67-95%) in patients with Grade 2-3, pT1a-b tumors (P = 0.002). CONCLUSIONS: Patients with well differentiated pT1a-b tumors form a subgroup with excellent long term prognosis, but a significant proportion of women with either moderately or poorly differentiated pT1a-b tumors or pT1c tumors ultimately die of the disease.     

Sarcomatoid differentiation as a prognostic factor for immunotherapy in metastatic renal cell carcinoma

BACKGROUND: The objective of the current study was to determine the significance of sarcomatoid differentiation as a prognostic factor for immunotherapy in metastatic renal cell carcinoma (RCC). METHODS: Patients with metastatic RCC were included in this study and were categorized according to sarcomatoid differentiation. RESULTS: Patients with sarcomatoid differentiation had more aggressive tumor characteristics than those without sarcomatoid differentiation. After immunotherapy, the median progression-free survival was 9.0 months (95% confidence interval [CI] 1.4-52.7) for patient without sarcomatoid differentiation and 3.2 months (95% CI 0.4-42.9) for patients with sarcomatoid differentiation, respectively (P=0.0001). The median overall survival was 22.2 months (95% CI 3.2-75.4) and 10.0 months (95% CI 0.7-60.1) in both groups. When comparing patients with sarcomatoid differentiation, there was no significant difference of overall survival in the immunotherapy group and the no immunotherapy group. Multivariate Cox proportional hazards model analysis showed that T stage (Hazard ratio [HR] 1.71; 95% CI 1.07-2.74; P=0.024), sarcomatoid differentiation (HR 2.18; 95% CI 1.30-3.66; P = 0.003), and the number of metastasis sites (HR 1.81; 95% CI 1.14-2.88; P=0.012) were independent predictors of progression-free survival. Sarcomatoid differentiation and the number of metastasis sites were independent prognostic predictors of overall survival. The estimated relative risks of sarcomatoid differentiation and the number of metastasis sites were 2.83 (95% CI 1.49-5.40; P=0.002) and 2.31 (95% CI 1.29-4.16; P=0.005), respectively. CONCLUSIONS: Our findings suggest that sarcomatoid differentiation is an important prognostic factor for immunotherapy in metastatic RCC.     

Intravaginal high-dose-rate brachytherapy for Stage IB (FIGO Grade 1, 2) endometrial cancer

PURPOSE: To evaluate the outcome of patients with Stage IB Grades 1 and 2 endometrial cancer treated with adjuvant high-dose-rate intravaginal brachytherapy. METHODS AND MATERIALS: Between November 1987 and October 1999, 233 patients with Stage IB FIGO Grades 1 and 2 were treated with postoperative adjuvant high-dose-rate intravaginal brachytherapy. The median dose was 21 Gy in 7 Gy/fraction given at 2-week intervals. The mean age was 60 years. All patients underwent simple hysterectomy. Comprehensive surgical staging, defined as pelvic washing and pelvic and paraaortic lymph nodes sampling, was done in 9% of patients. Patients with FIGO Grade 3, papillary serous cancer, or clear-cell cancer were excluded from this analysis. Complications were assessed in terms of late Radiation Therapy Oncology Group toxicity (Grade > or =3) of the gastrointestinal tract, genitourinary tract, and vagina. RESULTS: With a median follow-up of 57 months, the 5-year vaginal/pelvic control, disease-free survival, and overall survival rate was 96% (95% confidence interval [CI] 94-99%), 94% (95% CI 91-98%), and 94% (95% CI 91-98%), respectively. The influence on outcome of age, grade (1 vs. 2), depth of invasion (one-third or less or greater than one-third), capillary space-like invasion, lower uterine segment involvement, and comprehensive surgical staging was evaluated. None of these factors significantly affected the rate of vaginal/pelvic control. Only age > or =60 years influenced the outcome for disease-free and overall survival. The 5-year rate for both disease-free and overall survival was 90% (95% CI 84-97%) for patients > or =60 years old compared with 99% (95% CI 96-100%) for those <60 years (p = 0.03 and 0.005, respectively). Of 233 patients, 3 (1%) developed Grade 3 or greater complications, with a 5-year actuarial rate of 2% (95% CI 0-5%). Two patients developed Grade 3 genitourinary toxicity, and 1 Grade 4 vaginal toxicity. CONCLUSION: On the basis of this retrospective study, adjuvant postoperative high-dose-rate intravaginal brachytherapy provides excellent outcomes and acceptable morbidity. These results compare very favorably with those reported in the literature using surgery alone or with pelvic radiation.     

Phase II study of methotrexate,vinblastine, doxorubicin,and cisplatin in patients with squamous cell carcinoma of the upper respiratory or alimentary passages of the head and neck

BACKGROUND: The chemotherapy drugs methotrexate, vinblastine, doxorubicin, and cisplatin have shown activity in patients with recurrent or metastatic squamous cell carcinoma arising from the upper respiratory or alimentary passages of the head and neck. This study was undertaken to assess the antitumor activity and toxicity profile of the drug combination methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) in this patient population. METHODS: Patients with histologically confirmed unresectable, recurrent, or metastatic squamous cell carcinoma arising from the upper respiratory or alimentary passages of the head and neck were treated with MVAC over a 4-week cycle. The doses were as follows: 30 mg/m2 of methotrexate on Days 1, 15, and 22; 3 mg/m2 of vinblastine on Days 2, 15, and 22; 30 mg/m2 of doxorubicin on Day 2; and 70 mg/m2 of cisplatin on Day 2. The total cumulative dose of doxorubicin was not to exceed 450 mg/m2. Treatment was discontinued after four cycles for those whose disease remained stable. Patients were evaluated for chemotherapy response, progression free survival, and survival. RESULTS: Thirty-six patients were accrued onto this study between April 1993 and February 1996. One patient (3%) with a history of cardiac heart failure was declared ineligible. Severe leukopenia (leukocyte count < 2000 cells/m3) was observed in 55% of the patients during the first cycle of treatment and in 81% of the patients during the entire course of their treatment. The overall objective response rate over the first 4 cycles of treatment was 46% (90% confidence interval [CI], 33-60%). Two of the 18 patients who responded had a complete response. The median time to progression was 19 weeks, and 1-year progression free survival rate was 17% (95% CI, 8-36%). The median survival was 49 weeks, and the 1-year survival rate was 43% (95% CI, 29-63%). Among the 22 patients with unresected residual or recurrent disease, the median time to progression was 11 weeks, and 1-year progression free survival rate was 14% (95% CI, 5-39%), and median survival was 24 weeks, and the 1-year survival rate was 36% (95% CI, 21-63%). Among the 13 patients with metastatic disease, the median time to progression was 26 weeks, and the 1-year progression free survival rate was 23% (95% CI, 9-62%), the median survival was 54 weeks, and the 1-year survival rate was 54% (95% CI, 33-89%). CONCLUSIONS: Methotrexate, vinblastine, doxorubicin, and cisplatin is an active chemotherapy regimen in patients with recurrent or metastatic squamous cell cancer arising from the upper respiratory or alimentary passages of the head and neck.     

Intravaginal brachytherapy alone for intermediate-risk endometrial cancer

PURPOSE: Despite the results of the Gynecologic Oncology Group trial No. 99 (GOG#99), some unanswered questions still remain about the role of adjuvant radiotherapy (RT) for intermediate-risk endometrial cancer. First, can intravaginal brachytherapy (IVRT) alone substitute for external beam RT but without added morbidity? Second, is the high-risk (HR) definition from GOG#99 a useful tool to predict pelvic recurrence specifically? The purpose of this study was to try to answer these questions in a group of patients with Stage IB-IIB endometrial carcinoma treated with high-dose-rate (HDR) IVRT alone. METHODS AND MATERIALS: Between November 1987 and December 2002, 382 patients with Stage IB-IIB endometrial carcinoma were treated with simple hysterectomy followed by HDR-IVRT alone at our institution. Comprehensive surgical staging (CSS), defined as pelvic washings and pelvic/paraaortic lymph node sampling, was performed in 20% of patients. The mean age was 60 years (range, 29-92 years). Lymphovascular invasion (LVI) was present in 14% of patients. The median HDR-IVRT dose was 21 Gy (range, 6-21 Gy), given in three fractions. Complications were assessed in terms of late Radiation Therapy Oncology Group (Grade 3 or worse) toxicity of the GI tract, genitourinary GU tract, and vagina. RESULTS: With a median follow-up of 48 months, the 5-year vaginal/pelvic control rate was 95% (95% confidence interval [CI], 93-98%). On multivariate analysis, a poor vaginal/pelvic control rate correlated with age > or =60 years old (relative risk [RR], 3, 95% CI, 1-12; p = 0.01), International Federation of Gynecology and Obstetrics (FIGO) Grade 3 (RR, 9, 95% CI, 2-35; p = 0.03), and LVI (RR, 4, 95% CI, 1-13; p = 0.051). The depth of myometrial invasion and CSS, however, were not significant. With regard to pelvic control specifically, the presence of GOG#99 HR features did not affect the pelvic control rate. The 5-year rate for HR patients was 96% (95% CI, 90-100%) vs. 96% (95% CI, 94-99%) for those without HR disease (p = 0.48). Even when the CSS effect was taken into account, the influence of HR features on pelvic control was still not significant (p = 0.51). In contrast, pelvic control was significantly influenced when patients were grouped according to CSS and stage/grade substages. For those with Stage IB Grade 3-IIB and no CSS, the 5-year pelvic control rate was 86% compared with 97% for those with Stage IB Grade 3-IIB and CSS, 97% for Stage IB, Grade 1-2 without CSS, and 100% for those with Stage IB, Grade 1-2 and CSS (p = 0.027). The 5-year disease-free survival rate was 93% (95% CI, 90-96%). On multivariate analysis, poor disease-free survival correlated with age > or =60 years (RR, 5; 95% CI, 1-18; p = 0.002), FIGO Grade 3 (RR 5, 95% CI 2-17; p = 0.013), and LVI (RR 3, 95% CI 1-8; p = 0.054). Unlike pelvic control, disease-free survival was significantly affected by GOG#99 HR features, with a 5-year rate of 87% (95% CI, 76-99%) vs. 94% (95% CI, 91-97%) for those without HR features (p = 0.027). The 5-year overall and disease-specific survival rate was 93% and 97%, respectively. The overall 5-year actuarial rate of Grade 3 or worse complications was 1% (95% CI, 0-2%). CONCLUSION: Tumor grade, depth of invasion, and the use of CSS were better predictors of pelvic control than the GOG#99 HR factors. IVRT alone seemed to provide adequate tumor control with very low morbidity. Therefore, it seems prudent to consider it for intermediate-risk patients because of its superior therapeutic ratio compared with that for surgery alone or pelvic RT. Additional follow-up, however, with a larger number of patients is needed, especially for those with LVI.     

Early ipsilateral breast tumor recurrences after breast conservation affect survival: an analysis of the National Cancer Institute randomized trial

PURPOSE: To evaluate the effect of an ipsilateral breast tumor recurrence (IBTR) after breast-conservation therapy (BCT) on survival. METHODS AND MATERIALS: One hundred twenty-one women were randomized to BCT. Patients with an IBTR were analyzed to determine survival. Analysis was performed with Kaplan-Meier estimates, log-rank tests, and time-dependent covariate Cox models. RESULTS: At a median follow-up of 18.4 years, 27 patients had an IBTR. The median survival time after IBTR was 13.1 years. The 5-year survival rate was 91.8% (95% confidence interval [CI], 81.5-100%). The 10-year survival rate was 54.3% (95% CI, 35.8-82.6%). According to a Cox model with time-dependent covariates, the hazard ratio or relative risk of dying for those with an IBTR at <5.3 years after BCT relative to patients without an IBTR after BCT is 1.47 (95% CI, 1.02-2.12%; p = 0.04). The hazard ratio for those who relapse after 5.3 years is 0.59 (95% CI, 0.22-1.61%; p = 0.31). Age at randomization, original tumor size, and the presence of positive regional nodes at initial presentation were not found to be associated with decreased survival. CONCLUSIONS: There seems to be a significant association of early IBTR after BCT with decreased survival. Local control should be maximized.     

Treatment of primary, recurrent or inadequately resected high-risk soft-tissue sarcomas (STS) of adults: results of a phase II pilot study (RHT-95) of neoadjuvant chemotherapy combined with regional hyperthermia

The efficacy of thermochemotherapy in adult patients with primary, recurrent or inadequately resected non-metastatic high-risk soft-tissue sarcomas (STS) was assessed. 54 patients were prospectively treated with four cycles of etoposide, ifosfamide and doxorubicin (EIA) combined with regional hyperthermia (RHT) followed by surgery, another four cycles of EIA without RHT and external beam radiation. The objective response rate was 16% and at a median follow-up time of 57 months, the 4-year estimated rates of local failure-free survival (LFFS), distant metastasis-free survival (DMFS), event-free survival (EFS) and overall survival (OS) were 59% (95% confidence interval (CI) 45-73%), 59% (95% CI 44-73%), 26% (95% CI 14-38%) and 40% (95% CI 27-53%), respectively. OS was in favour of patients responding to neoadjuvant treatment (P=0.073). In comparison to a preceding phase II study including pre- and postsurgical thermochemotherapy (RHT-91), at a 4-year follow-up the RHT-95 study cohort showed an inferior LFFS rate (P=0.027), but this did not affect DMFS (P=0.558) or OS (P=0.126). Hence, postsurgical thermochemotherapy seems critical for local tumour control without affecting survival.     

Genetic variants of NBS1 predict clinical outcome of platinum-based chemotherapy in advanced non-small cell lung cancer in Chinese

Objective: NBS1 plays a key role in the repair of DNA double-strand break (DSB). We conducted this study to investigate the effect of two critical polymorphisms (rs1805794 and rs13312840) in NBS1 on treatment response and prognosis of advanced non-small cell lung cancer (NSCLC) patients with platinum-based chemotherapy. Methods: Using TaqMan methods, we genotyped the two polymorphisms in 147 NSCLC patients. Odds ratios (ORs) and their 95% confidential intervals (CIs) were calculated as a measure of difference in the response rate of platinum-based chemotherapy using logistic regression analysis. The Kaplan-Meier and log-rank tests were used to assess the differences in progression-free survival (PFS) and overall survival (OS). Cox proportional hazards model was applied to assess the hazard ratios (HRs) for PFS and OS. Results: Neither of the two polymorphisms was significantly associated with treatment response of platinum-based chemotherapy. However, patients carrying the rs1805794 CC variant genotype had a significantly improved PFS compared to those with GG genotype (16.0 vs. 8.0 months, P = 0.040). Multivariable cox regression analysis further showed that rs1805974 was a significantly favorable prognostic factor for PFS [CC/CG vs. GG: Adjusted HR = 0.62, 95% CI: 0.39-0.99; CC vs. CG/GG: Adjusted HR = 0.56, 95% CI: 0.32-0.97). Similarly, rs13312840 with a small sample size also showed a significant association with PFS (CC vs. CT/TT: Adjusted HR = 25.62, 95% CI: 1.53-428.39). Conclusions: Our findings suggest that NBS1 polymorphisms may be genetic biomarkers for NSCLC prognosis especially PFS with platinum-based chemotherapy in the Chinese population.     

Survival Rate and Prognostic Factors for Colorectal Cancer in Sabah,Borneo, Malaysia: A Retrospective Cohort of a Population-Based Study

Background: Colorectal cancer is a major public health problem with significant number of cases and death in the population. This study aimed to determine the 5-year overall survival rate and the prognostic factors for colorectal cancer patients in Sabah. Methods: This was a retrospective cohort study conducted using secondary data from Malaysian National Cancer Registry (MNCR) database. A 5-year overall survival and the median survival time were determined with Kaplan-Meier survival curve. Cox regression analysis was done to determine the prognostic factors on survival. Results: A total of 1,152 patients were included in this study. The majority of the patients had colon cancer and presented at late stage (stage III and IV) as compared to early stage (stage I and II). From the analysis, the 5-year overall survival for colorectal cancer was 23.2% (95% CI: 21.8, 24.6) and the median survival time was 16 months (95% CI: 14.3, 17.7).  Higher survivals are seen in males (23.6%, 95% CI: 20.4, 24.7), aged 50-74 years old (24.2%, 95% CI: 22.4, 26.0), Chinese (25.5%, 95% CI: 23.0, 28.0), lived in Keningau (25.6%, 95% CI: 20.8, 30.4), colon as primary tumor site (24.5%, 95% CI: 22.5, 26.4), diagnosed with stage I (55.6%, 95% CI: 48.7, 62.5) and received surgery with chemotherapy or radiotherapy (31.3%, 95% CI: 27.8, 34.8). The significant prognostic factor was the stage at diagnosis. Patients with stage IV colorectal cancer (HR: 11.18; 95% CI: 3.48, 35.93) had eleven times risk of dying as compared to stage I. Conclusion: The survival rate for colorectal cancer patients in Sabah was comparatively lower than other states in Malaysia and in some Asian countries. Those patients who presented at later stage had poorer survival. Health promotion and community-based screening program should be emphasized in addition to encouraging early diagnosis to improve survival.     

Role of fractionated external beam radiotherapy in hemangioblastoma of the central nervous system

PURPOSE: To assess the clinical outcomes and toxicity in patients receiving fractionated external beam radiotherapy (EBRT) for hemangioblastoma of the central nervous system, treated at two Canadian radiation oncology institutions. METHODS AND MATERIALS: Between January 1980 and December 2004, the data of all patients receiving EBRT for central nervous system hemangioblastoma were retrospectively reviewed. The patient, tumor, and treatment characteristics were collected and overall survival, disease-free survival, and EBRT-related toxicities assessed. RESULTS: A total of 18 cases, 5 associated with von Hippel-Lindau disease (VHL) and 13 sporadic (non-VHL), with a total 31 lesions, were documented. These were located in the cerebellum in 20 and spinal cord in 8 patients. EBRT was delivered for recurrence in 12, adjuvantly for residual disease in 4, and definitively in 2. The EBRT schedules ranged from 50.0 to 55.8 Gy in 1.8-2.0-Gy daily fractions (n = 17), typically with parallel-opposed fields to the cerebellar target volumes and direct posterior fields for spinal disease. At a median follow-up of 5.1 years (range, 0.1-14.5), the 5-year OS rate was 69% (95% confidence interval [CI], 50-96%), decreasing to 30% (95% CI, 10-87%) at 10 years. The disease-free survival rate at 5 and 10 years was 57% (95% CI, 37-87%) and 30% (95% CI, 11-83%), respectively. The outcomes differed according to VHL status. The 5-year OS rate was 100% for those with VHL compared with 55% (95% CI, 32-95%) for those with non-VHL disease (log-rank p = 0.003), and the 5-year disease-free survival rate was 80% (95% CI, 52-100%) with VHL compared with 48% (95% CI, 26-89%) without (log-rank p = 0.036). CONCLUSIONS: Fractionated EBRT has a role in the management of extensive intracranial and/or spinal cord disease, the adjuvant treatment of residual postoperative disease, and the treatment of recurrence. More favorable outcomes were reported for VHL-associated lesions than for sporadic cases.     

Locoregional failure of postmastectomy patients with 1-3 positive axillary lymph nodes without adjuvant radiotherapy

PURPOSE: To analyze the incidence and risk factors for locoregional recurrence (LRR) in patients with breast cancer who had T1 or T2 primary tumor and 1-3 histologically involved axillary lymph nodes treated with modified radical mastectomy without adjuvant radiotherapy (RT). MATERIALS AND METHODS: Between April 1991 and December 1998, 125 patients with invasive breast cancer were treated with modified radical mastectomy and were found to have 1-3 positive axillary nodes. The median number of nodes examined was 17 (range 7-33). Of the 125 patients, 110, who had no adjuvant RT and had a minimum follow-up of 25 months, were included in this study. Sixty-nine patients received adjuvant chemotherapy and 84 received adjuvant hormonal therapy with tamoxifen. Patient-related characteristics (age, menopausal status, medial/lateral quadrant of tumor location, T stage, tumor size, estrogen/progesterone receptor protein status, nuclear grade, extracapsular extension, lymphovascular invasion, and number of involved axillary nodes) and treatment-related factors (chemotherapy and hormonal therapy) were analyzed for their impact on LRR. The median follow-up was 54 months. RESULTS: Of 110 patients without RT, 17 had LRR during follow-up. The 4-year LRR rate was 16.1% (95% confidence interval [CI] 9.1-23.1%). All but one LRR were isolated LRR without preceding or simultaneous distant metastasis. According to univariate analysis, age <40 years (p = 0.006), T2 classification (p = 0.04), tumor size >==3 cm (p = 0.002), negative estrogen receptor protein status (p = 0.02), presence of lymphovascular invasion (p = 0.02), and no tamoxifen therapy (p = 0.0006) were associated with a significantly higher rate of LRR. Tumor size (p = 0.006) was the only risk factor for LRR with statistical significance in the multivariate analysis. On the basis of the 4 patient-related factors (age <40 years, tumor >==3 cm, negative estrogen receptor protein, and lymphovascular invasion), the high-risk group (with 3 or 4 factors) had a 4-year LRR rate of 66.7% (95% CI 42.8-90.5%) compared with 7.8% (95% CI 2.2-13.3%) for the low-risk group (with 0-2 factors; p = 0.0001). For the 110 patients who received no adjuvant RT, LRR was associated with a 4-year distant metastasis rate of 49.0% (9 of 17, 95% CI 24.6-73.4%). For patients without LRR, it was 13.3% (15 of 93, 95% CI 6.3-20.3%; p = 0.0001). The 4-year survival rate for patients with and without LRR was 75.1% (95% CI 53.8-96.4%) and 88.7% (95% CI 82.1-95.4%; p = 0.049), respectively. LRR was independently associated with a higher risk of distant metastasis and worse survival in multivariate analysis. CONCLUSION: LRR after mastectomy is not only a substantial clinical problem, but has a significant impact on the outcome of patients with T1 or T2 primary tumor and 1-3 positive axillary nodes. Patients with risk factors for LRR may need adjuvant RT. Randomized trials are warranted to determine the potential benefit of postmastectomy RT on the survival of patients with a T1 or T2 primary tumor and 1-3 positive nodes.     

External-beam radiotherapy for localized or locally advanced prostate cancer in Japan: a multi-institutional outcome analysis

BACKGROUND: The outcomes of patients with localized or locally advanced prostate cancer treated with external-beam radiotherapy are not well known in Japan. METHODS: Thirty-four institutions combined data on 679 patients with localized or locally advanced prostate cancer treated with a total dose >/=60 Gy between 1995 and 2002. RESULTS: With a median follow-up of 46 months, the 5-year overall, clinical progression-free, and biochemical relapse-free survival rate were 93.0, 95.3 and 71.9% for all patients, respectively. The 5-year progression-free, and biochemical relapse-free survival rates according to the risk group were 100%, 90.8% in the low-risk group, 98.3%, 75.7% in the intermediate-risk group and 93.6%, 67.6% in the high-risk group, respectively. The multivariate analysis for biochemical relapse-free survival revealed that prostate-specific antigen (relative risk, 1.002; 95% CI, 1.001-1.003; P = 0.0041), Gleason score (relative risk, 1.166; 95% CI, 1.046-1.302; P = 0.0055), T classification (relative risk, 2.897; 95% CI, 1.999-4.230; P = 0.0000), pelvic irradiation (relative risk, 2.042; 95% CI, 1.328-3.273; P = 0.0008), and androgen abletion (relative risk, 0.321; 95% CI, 0.240-0.427; P = 0.0000) were significant prognostic factors. Only 1.1% of patients experienced late morbidity of Grade 3. CONCLUSION: Radiotherapy for prostate cancer seemed to be effective, with little risk of normal tissue complications.