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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.

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.)

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.

Objective: In the post-radiation patient, late vascular sequelae and fibrosis predispose women to poor tissue healing, such that small tissue injuries could theoretically evolve into much larger ones such as fistulae. We sought to determine if a correlation exists between invasive procedures such as post-treatment biopsies and the subsequent development of gynecologic fistulae., Methods: A retrospective review was performed evaluating all patients treated for cervical cancer at our institution between 1997 and 2010. Biopsies or pelvic surgeries were included if performed within the radiated field, and evaluated in a multivariate predictive model for development of gynecologic fistulae., Results: Out of 325 total patients, 27 patients with fistulae were identified (8.2%). 14 fistulae (51.9%) were considered toxicity-related, 6 (22.2%) resulted from primary disease, and 7 (25.9%) were attributable to recurrent disease. Eighty-nine patients underwent an invasive procedure (55 biopsies and 34 pelvic surgeries). Recurrent and/or residual cancer was found in 28 (31.5%) specimens, and of the 61 patients who underwent an invasive procedure and were not found to have evidence of recurrent disease, 9 (14.8%) subsequently developed a fistula at a median 3.08 months. An elevated dose of radiation to the rectum (OR 1.001 for dose >72 Gy, p=0.0005), advancing tumor stage (OR 5.38 for stage III, OR 10.47 for stage IV, p=0.0288), and a post-radiation biopsy (OR 5.27, p=0.013) were significantly associated with fistula development., Conclusions: Performing a biopsy in an irradiated field is associated with a relatively low yield and significantly contributes to the risk for fistula development., (Published by Elsevier Inc.)

Poorly differentiated head and neck neuroendocrine neoplasms are very rare. Surgical resection alone is insufficient to control the disease because of the high incidence of metastases. However, due to the lack of randomised clinical trials, treatment recommendations for this cancer vary considerably and are based on a limited number of small retrospective studies. We performed a retrospective analysis of all patients treated at our institution between 2003 and 2011. We assessed the stage of disease, type of therapy, toxicity, treatment response, time to progression and overall survival for all cases. Ten patients received combined modality treatment with chemotherapy in addition to surgery or radiation or both. According to Response Evaluation Criteria In Solid Tumours (RECIST) criteria, six of nine evaluable patients achieved complete remission and three patients had a partial remission. The mean duration of response was 358 days, with a range from 141 to 1080 days. The overall 1-year survival rate was 88%; however, only approximately 50% of patients were alive after 2 years. Multimodality treatment concepts induce high initial remission rates in poorly differentiated neuroendocrine head and neck carcinomas. However, the time to relapse is usually short, and therefore long-term prognosis of this rare head and neck tumour remains poor., (© 2013 John Wiley & Sons Ltd.)

Background: The optimal management of brain metastases from uterine cervix cancer (UCC) is not well defined because of the rarity of the condition and the scarcity of published reports. Here we report our experience with stereotactic radiosurgery for the management of brain metastases from UCC., Methods: Thirteen consecutive patients with brain metastases from UCC were managed with a Leksell gamma-knife at our institution between January 2003 and December 2010. Clinical features and radiosurgical outcomes of patients were analyzed retrospectively., Results: Gamma-knife radiosurgery (GKRS) was chosen as the only treatment in four patients and performed in combination with whole-brain radiotherapy (WBRT) in nine patients. GKRS was conducted simultaneously with WBRT within a 1-month interval in six patients and was chosen as the salvage treatment after WBRT in three patients. The mean number of metastatic brain lesions per patient was 5.7 (range, 1-16). The median cumulative tumor volume was 23.7 cm(3) (range, 2.7-40.2 cm(3)), and the median marginal dose covering the tumors was 14 Gy of a 50 % isodose line (range, 8-25 Gy). Nine patients showed relief of main neurologic symptoms after GKRS. The median length of time that the patients spent in an improved neurologic state was 11.1 weeks (range, 2-39.6 weeks). The local and distant control rates were 66.7 % and 77.8 %, respectively. The median survival from the date of GKRS until death was 4.6 months (range, 1.0-15.9 months). The 6-month and 12-month survival rates after GKRS were 38 and 15 %, respectively., Conclusions: GKRS could be an efficient palliative measure to relieve neurologic symptoms caused by brain metastasis from UCC.

Purpose: To measure the displacement of the tumor of the gross tumor volume (GTV) of thoracic esophageal cancer in the calm states of end-inspiration and end-expiration for determining the internal margin of the GTV (IGTV)., Methods: Twenty-two patients with thoracic esophageal cancer who were unable to undergo surgery were identified in our hospital. The patients received radiotherapy. By using 16-slice spiral computed tomography (CT), we acquired the calm states of end-inspiration and end-expiration. The displacement and volume changes in tumor target volume were measured, and the changes were analyzed to determine if these were associated with the tidal volume and the location and length of the target volume V. In the end, we analyzed the displacement of tumor target volume and calculated the internal margin of the GTV by empirical formula., Results: The average tidal volume was 463.6 ml. The average GTV at end-inspiration was 33.3 ml and at end-expiration was 33.35 ml. Three was not any significant between two groups (T=-0.034, P>0.05). The IGTV (X-axis direction) was 3.09 mm for the right sector and 4.08 mm for the left border; the IGTV (Z-axis direction) was 3.96 mm for the anterior border and 2.83 mm for the posterior border; and the IGTV (Y-axis direction) was 7.31 mm for the upper boundary (head direction) and 10.16 mm for the lower boundary (feet direction). The motion of the GTV showed no significant correlation with the tidal volume of patients and the length of the tumor, but in relation to the tumor location, the displacement of the lower thoracic and the middle thoracic target volumes occurred in the direction of the anterior and right, which were not significantly different (T=0.859, 0.229, P>0.05) The significant differences were observed for the other directions (P<0.05)., Conclusions: Because of respiratory and organ movements, the displacement of the tumor target volume was different in all directions. Therefore, we recommend that expansion of the planning target volume during clinical radiation treatment needs to include the displacement of the tumor target volume caused by respiratory and organ movements during each radiotherapy session., (Copyright © 2012 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Background: We present a comprehensive analysis of both therapy-induced severe late toxicity and outcome in a cohort of cervical cancer patients following radiation who were treated according to current guidelines and discuss the methodologic problems of systematically reporting these cases. We introduce a revised concept of reporting treatment failure., Patients and Methods: The records of 128 cervical cancer patients who received radiation from 2003 to 2008 were reviewed., Results: Thirteen patients (10.2%) developed severe late toxicity. The combination of heavy smoking and cardiovascular diseases was found to be a significant contributing factor (HR 6.55, 95% CI 0.99-43.49, p = 0.048). Thirty patients (23.4%) experienced treatment failure. Of these, 12 (9.4%) were defined to have persistent disease, and 18 (14.0%) developed recurrent disease. Patients with recurrent disease had significantly better survival time (p < 0.001). Compared with the persistence subgroup, they had significantly more often multiple sites of relapse (66.7 vs. 8.3%, p = 0.002) and the sites were more often diagnosed outside the pelvis (70.7 vs. 7.7%, p < 0.001). Early disease stages (OR 4.46, 95% CI 1.87-10.63, p < 0.001) and severe late toxicity (p = 0.037) were found to be significant factors for an improved disease-free survival., Conclusions: A comprehensive depiction of both late therapy-related toxicity and treatment failure requires precise clinical descriptions and analyses of the clinical courses. Our new concept to differentiate treatment failure following radiotherapy in cervical cancer into persistent and recurrent disease permits a clear differentiation between distinct subgroups of patients with regard to prognosis and clinical presentation and will lead to a more precise description of these cases in the future.

Purpose: To determine clinical factors for predicting the frequency and severity of esophageal stenosis associated with tumor regression in radiotherapy for esophageal cancer., Methods and Materials: The study group consisted of 109 patients with esophageal cancer of T1-4 and Stage I-III who were treated with definitive radiotherapy and achieved a complete response of their primary lesion at Kyushu University Hospital between January 1998 and December 2007. Esophageal stenosis was evaluated using esophagographic images within 3 months after completion of radiotherapy. We investigated the correlation between esophageal stenosis after radiotherapy and each of the clinical factors with regard to tumors and therapy. For validation of the correlative factors for esophageal stenosis, an artificial neural network was used to predict the esophageal stenotic ratio., Results: Esophageal stenosis tended to be more severe and more frequent in T3-4 cases than in T1-2 cases. Esophageal stenosis in cases with full circumference involvement tended to be more severe and more frequent than that in cases without full circumference involvement. Increases in wall thickness tended to be associated with increases in esophageal stenosis severity and frequency. In the multivariate analysis, T stage, extent of involved circumference, and wall thickness of the tumor region were significantly correlated to esophageal stenosis (p = 0.031, p < 0.0001, and p = 0.0011, respectively). The esophageal stenotic ratio predicted by the artificial neural network, which learned these three factors, was significantly correlated to the actual observed stenotic ratio, with a correlation coefficient of 0.864 (p < 0.001)., Conclusion: Our study suggested that T stage, extent of involved circumference, and esophageal wall thickness of the tumor region were useful to predict the frequency and severity of esophageal stenosis associated with tumor regression in radiotherapy for esophageal cancer., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: To explore factors affecting the survival in patients after radical resection of esophageal carcinoma, and to provide a valuable reference for selecting treatment protocol after surgery., Methods: Clinicopathological data of 618 esophageal cancer patients who underwent radical resection at the Fourth Hospital of Hebei Medical University from May 2002 to June 2006 were collected and reviewed in this study. All patients had no cancer history, did not receive preoperative radiotherapy or chemotherapy, and had Karnofsky performance scores ≥ 70. Univariate analysis was performed by using log-rank test to determine predictors of survival, and multivariable analysis was performed by a Cox regression model., Results: The overall 1-, 3-, 5-year survival rates were 83.32%, 53.33%, 36.02%, respectively, and the median survival time was 38.33 months. The Cox regression analysis showed that operation mode, intraoperative findings of the extent of tumor invasion, pathological T stage, and the number of metastatic lymph nodes were significant predictors of survival. For patients with lymph node metastasis, the overall 1-, 3-, and 5-year survival rates did not significantly differ between the operation alone group and the postoperative prophylactic radiotherapy group. For patients without lymph node metastasis, the 1-, 3-, and 5-year survival rates were 94.34%, 51.55%, and 34.41%, respectively, in the postoperative radiotherapy group, significantly higher than those in the operation alone group (63.08%, 23.30% and 4.36%; χ(2) = 15.99, P < 0.01)., Conclusions: The independent prognostic factors of esophageal cancer patients after radical resection include the operation mode, intra-operative findings of the extent of tumor invasion, pathological T stage, the number of lymph node metastasis and the number of regions of lymph node metastasis. Postoperative prophylactic radiotherapy is beneficial for esophageal cancer patients with lymph node metastasis.

Objective: This study is to evaluate the changes in tumor perfusion CT before and after chemotherapy/radiotherapy, and its feasibility in assessing early treatment response and predicting the prognosis in lung cancer patients., Methods: Perfusion CT scan was performed on a multidetector CT scanner with power injection of contrast medium (50 ml, 300 mg I/ml, 4 ml/s) in the patients before and after chemotherapy/radiotherapy. The treatment response after chemotherapy/radiotherapy was assessed by RECIST. The correlation of pre- and post-treatment tumor perfusion changes with progression-free survival (PFS) and overall survival (OS) was analyzed., Results: The patients were divided into two groups according to PS changs. In the increased PS group (n = 13), the PS after treatment was significantly higher than that before treatment (20.1 +/- 7.5 ml x min(-1) x 100 g(-1) vs. 13.7 +/- 6.2 ml/min/100 g, P = 0.013), while in the decreased PS group (n = 11), the PS after treatment was significantly lower than that before treatment (8.2 +/- 5.5 ml x min (-1) x 100 g(-1) vs. 15.3 +/- 5.1 ml x min(-1) x 100 g(-1), P = 0.000). No significant differences were observed in BF, BV, and MTT in both groups. The median PFS of PS increased group and decreased groups was 4.2 months and 19.0 months, respectively, (P = 0.000), and the median OS was 7.9 months and 19.3 months, respectively (P = 0.002)., Conclusion: Perfusion CT may have a potential application in predicting the prognosis of lung cancer after chemotherapy/radiotherapy, and PS increase after treatment may indicate a poor survival.

It is important to monitor tumor movement during radiotherapy. Respiration-induced motion affects tumors in the thorax and abdomen (in particular, those located in the lung region). For image-guided radiotherapy (IGRT) systems, it is desirable to minimize imaging dose, so external surrogates are used to infer the internal tumor motion between image acquisitions. This process relies on consistent correspondence between the external surrogate signal and the internal tumor motion. Respiratory hysteresis complicates the external/internal correspondence because two distinct tumor positions during different breathing phases can yield the same external observation. Previous attempts to resolve this ambiguity often subdivided the data into inhale/exhale stages and restricted the estimation to only one of these directions. In this study, we propose a new approach to infer the internal tumor motion from external surrogate signal using state augmentation. This method resolves the hysteresis ambiguity by incorporating higher-order system dynamics. It circumvents the segmentation of the internal/external trajectory into different phases, and estimates the inference map based on all the available external/internal correspondence pairs. Optimization of the state augmentation is investigated. This method generalizes naturally to adaptive on-line algorithms.

Objective: To evaluate single photon emission computed tomography (SPECT) lung perfusion in predicting radiation pneumonitis in lung cancer patients., Methods: From April 2003 to March 2004, 31 lung cancer patients treated with radical radiotherapy received SPECT lung perfusion scans, among whom, 23 had had perfusion scans both before and at the time of 40 Gy irradiation. The perfusion changes in the region of interest (ROI) after irradiation were obtained through comparing post-radiotherapy with pre-radiotherapy average proportion of SPECT counts within the ROI relative to average counts of the whole lung. Endpoint was defined as grade 2 and above radiation pneumonitis according to RTOG criteria., Results: Lung perfusion defect was observed in all the patients at baseline. > or = grade 2 lung perfusion defect was found in 68.2% (15/22) of patients with central lesion and in 22.2% (2/9) of patients with peripheral lesions (P = 0.04). Seventy percent of the patients (16/23) experienced improved perfusion at 40 - 50 Gy. > or = grade 2 radiation pneumonitis was observed in 12 patients (38.7%) in the whole group, with 6 in those with grade 1 perfusion defects and another 6 in > or = grade 2 group, respectively; Of the 23 patients who had had both pre- and post-radiotherapy SPECT perfusion scan, 5 > or = grade 2 radiation pneumonitis occurred in the 16 perfusion-improved patients and 3 in the 7 unimproved patients., Conclusion: There is no significant correlation between radiation pneumonitis and the extent of perfusion defect either before or after 40 - 50 Gy irradiation based on our limited data analysis in this series.

Skeletal muscle metastases from lung cancer are rare, and the optimal treatment strategy is unknown. Three cases of skeletal muscle metastases from lung cancer are described. In 2 patients surgical biopsy of muscle swelling disclosed the presence of the lung tumor; the first patient underwent lung resection to remove the primary lesion, the second was not operable because of the metastatic extension of the disease. In the third patient muscle metastasis was observed and excised after lung resection. Adenocarcinoma, squamous cell, and small cell carcinoma were the histologic types diagnosed. Various regimens of radiotherapy and chemotherapy were adopted. Survival times were 3, 6, and 30 months.

Objectives: To observe in a clinical trial the feasibility, tolerance, and efficacy of reirradiation by three-dimensional conformal radiotherapy (3D-CRT) for locoregionally recurrent lung carcinoma after external beam radiotherapy (EBRT)., Materials and Methods: Between June 1999 and March 2001, 23 lung carcinoma patients with locoregional recurrence after EBRT were enrolled in this study. Of the 23 patients, 21 were men and 2 were women (median age 68 years, range 43-79). At the first course of RT, 9 patients had squamous cell carcinoma, 7 adenocarcinoma, and 7 small cell carcinoma. The interval between the first course of RT and recurrence varied from 6 to 42 months (median 13). The median dose of the first course of RT was 66 Gy (range 30-78). Reirradiation was carried out using 3D-CRT and only covered the radiographic lesions. The median dose of reirradiation was 51 Gy (range 46-60), which was delivered by a conventionally fractionated schedule (i.e., 1.8-2.0 Gy/fraction, 5 fractions/wk). The toxicity was assessed according to the Radiation Therapy Oncology Group criteria., Results: The median follow-up time was 15 months (range 2-37). Acute radiation esophagitis occurred in 9% of patients (Grade 1-2). Acute radiation pneumonitis developed in 22% of patients (Grade 1-2). No cases of acute Grade 3 or greater toxicity had been recorded at last follow-up. Pulmonary fibrosis was observed in 26% of patients (Grade 2-3); no other severe late complications have been observed. The 1- and 2-year survival rate was 59% and 21%, respectively. The locoregional progression-free rate at 1 and 2 years was 51% and 42%, respectively., Conclusions: Reirradiation using 3D-CRT was tolerated by this group of recurrent lung carcinoma patients without severe complications. The 2-year outcome was encouraging. Reirradiation with 3D-CRT can be considered an option for the management of locoregionally recurrent lung carcinoma.

A 52-year-old man was admitted to our hospital on October, 1997 with complains of left anterior chest pain. A chest X-ray and computed tomography on admission showed evidence of a mass in the left anterior mediastinum. The patient was treated with combination chemotherapy [cisplatin (CDDP), etoposide (VP-16)] and radiation therapy (2 gray x 25 days), preoperatively. Median sternotomy revealed a tumor invading into the left anterior chest wall, the pericardium, and partial pleura. The tumor was extirpated with combined resection of invaded organs. Microscopically and immunohistochemically, the tumor was diagnosed mixed small cell and undifferentiated squamous cell carcinoma documented by Snover et al. The patient was discharge on March 1998, but 2 years later after operation, he was dead by recurrent. We reported a rare case of thymic carcinoma.

Background and Method: The effect of overall treatment time on therapeutic outcome was analyzed comparing the randomized trials on accelerated fractionation for the different tumor entities. Only studies using radiotherapy as the definitive locoregional treatment modality were included., Results and Conclusion: Randomized studies were performed for squamous cell carcinomas of the head and neck region as well as for small-cell and non-small-cell carcinomas of the lung. These studies showed, that locoregional control can be improved by accelerated fractionation in comparison to conventional fractionation with the same total dose. With the same antitumor effectiveness of both fractionation schedules, total dose can be reduced using accelerated fractionation.

Four hundred and eighty patients with histologically confirmed carcinoma of the uterine cervix were randomized into 2 groups to either receive hypofractionated radiotherapy (HF--230 patients--study group) or conventional fractionated radiotherapy (CFR--250 patients--control group) between December 1988 and November 1992 at the Radiotherapy Department, University College Hospital, Ibadan. The 5-year survival rate for HF patients in Stages I, II, III and IV were, respectively, 91.3%, 67.2%, 40.2% and 18.0% while for CFR patients in Stages I, II, III and IV were respectively, 92.8%, 69.2%, 42.5% and 19.6%. Though early radiation adverse effects were similar in CFR and HF patients, marked late adverse radiation effects were observed in HF patients than in CFR patients. Complete response rate and local tumour controls were found to be similar in the HF and CFR patients. This study revealed that with similar 5-year survival, complete response rate and local tumour control in HF and CFR patients while a significantly higher late radiation adverse effects were recorded in HF patients, conventional fractionated radiotherapy is the preferred form of radiation therapy in the management of carcinoma of the uterine cervix. Administration of hypofractionated radiotherapy for cervical cancer patients with the aim of maximizing the use of few available radiotherapy facilities, as currently obtained in some radiotherapy centres in Nigeria will result in high post treatment morbidity.

Results are submitted of study into effects of microwave resonance therapy (MRT) on parameters characterizing cell immunity in those lung cancer patients having undergone a radical operation. This study comprised 58 patients as the main group, with 31 patients being controls. Indices for cell immunity were also studied in 20 donors. There was a rise in T-lymphocytes after MRT in the postoperative period. MRT contributed to prolongation of patients' lives, reduction of the incidence of chemotherapy-related dyspeptic complications and that of leukopenia cases by 8 and 9 percent respectively.

Synchronous primary lung cancer (SPLC) occurs in up to 0.5% of patients with lung cancer. Among SPLC cases, coexistence of small cell carcinoma (SCLC) and non-small cell carcinoma has been reported in a very small fraction. Futhermore, there have been no reports discussing treatment and prognosis of SPLC presenting with SCLC and NSCLC. We report on two cases of SPLC presenting SCLC in limited stage and operable NSCLC. One patient developed synchronously SCLC and adenocarcinoma of the lung, while the other SCLC and squamous cell carcinoma of the lung. The clonal origin of these synchronous lung cancers was evaluated using immunohistochemical and polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analyses. Both of the patients were diagnosed based on transbronchial lung biopsy (TBLB) and mediastinoscopic biopsy. They were successfully treated with chemoradiotherapy and adjuvant surgery, and are now doing well without any signs of tumor progression for about one year. In both cases, a response of mediastinal lymph node for concurrent chemoradiotherapy was quite different from that of the mass in the lung field. In case 2, p53 mutation was observed in the SCLC tissue, but not in the NSCLC tissue by PCR-SSCP. In both cases, carcinoembryonic antigen was documented in the NSCLC tissue, but not in the SCLC tissue by immunohistochemical staining. This report indicates the importance of the accurate diagnosis of SPLC by employing TBLB and/or media-stinoscopy for the optimal treatment of patients having SPLC presenting with SCLC and NSCLC. Diagnostic criteria and standard treatment of this disease should be established.

Background and Purpose: Metastasis to the brain develops in 25% of all patients with lung cancer. Although the outcome is usually poor, there seems to be a subset of patients with favorable prognostic factors who may live longer. Prognostic factors were analyzed retrospectively in 103 patients with brain metastases from lung carcinoma to identify patients who would benefit from more intensive treatment strategies., Materials and Methods: Between October 1991 and December 1994, 103 patients with brain metastasis from lung cancer were irradiated with palliative intent. Palliation was defined as 50% or more regression of neurological signs and symptoms 2 weeks after the completion of cranial radiotherapy. Local (related to the lung tumor) symptom status at the time of brain metastasis, the presence of metastases other than brain, multiplicity of brain metastases on CT scan and time of occurrence of brain metastasis were the factors which were evaluated with multivariate analysis., Results: Palliation was accomplished in 85% of cases. Palliation duration ranged from 0.5 to 54 months (median 3 months). The overall median survival was 5 months. Only one patient is under follow-up without any symptoms related to the brain metastasis. According to the multivariate analysis survival was significantly decreased in the presence of symptoms related to the primary tumor (P = 0.001)., Conclusion: The presence of symptoms related to the primary tumor at the time of brain metastasis is one of the factors that can be used to distinguish patients with a favorable outcome. In patients with favorable prognostic factors and thus longer survival probability, the role of boost dose after whole brain radiotherapy or surgical resection in suitable cases needs to be investigated.

To assess clinical and bronchoscopic evolution as well as outcome in patients treated with high dose rate (HDR) endobronchial brachytherapy in order to determine its effectiveness for treating malignant airway obstruction. From May 1993 to January 1996, 10 patients (9 men and 1 woman) with bronchogenic carcinoma received 24 HDR endobronchial treatments. The mean age was 61.9 years (range 34 to 78 years). Inclusion criteria were, for palliative treatment, incurable endobronchial cancer, and, for curative treatment, residual tumor in the margins after resection, or endobronchial tumor that could not be treated surgically. Exclusion criteria were site of lesion unsuitable for placement of the brachytherapy catheter, life expectancy less than two months, Karnofsky index less than 60 or absence of signed consent from the patient. Response criteria was either complete or partial for symptoms and endobronchial tumor. Ten patients received 24 HDR endobronchial treatment from and HDR source of I192 radiation with remote afterloading. A flexible bronchoscope was passed down the bronchial tree toward the area affected by the tumor. At intervals of one week, four separate fractions between 5 and 10 Gy were delivered to a depth of 0.5 to 1 cm and a length of 1 to 5 cm. One month after the last session, each patient underwent endoscopic examination with removal of a histology specimen. Response was considered complete based on clinical signs in 66%; response was complete based on endoscopy in 50%. Three patients died within the first year after treatment and one patient did not return for a follow-up examination. Five patients who had been followed for less than one year were still living. The remaining patient was living 18 months after treatment. All tolerated the treatments well, showing neither early nor late complications. HDR endobronchial brachytherapy is effective both for preventing and relieving malignant endobronchial obstruction. Response to therapy is good, as shown by clinical symptoms and endobronchial examination. HDR endobronchial brachytherapy can cure in carefully selected patients.

This paper reports a prospective survey of 173 patients with nonoperable lung cancer between January. 1, 1983 to March. 1, 1985. The follow-up rate was 97.7% over five years. Fourteen factors including sex, age, course of disease before treatment, clinical stage, performance status, size of mass, metastatic status, hemoglobin before treatment, short-term response to treatment and so on which might influence long term survival were studied by univariate analysis (Kruskal-Wallis test for Kaplan-Meier survival curve) and by multivariate analysis (Cox's proportional hazad model and audio-visual chart test for goodness of fit). Multivariate analysis using Cox's model revealed 6 significant prognostic factors: performance status, short-term response to treatment, clinical stage, hemoglobin before treatment, smoking index and method of treatment. The survival prediction equation was chi 2 = 72.14, nu = 6, P < 0.0001. The results indicate that the performance status and the CR rate of the initial treatment, among other things, is the major factors affecting prognosis.

From April 1992 to December 1994, a total of 61 patients with carcinoma of the cervix were treated with curative intent using initially external beam therapy followed by high dose rate brachytherapy. On reviewing 57 patients with adequate follow-up data, the local failure rate was found to be 12.3% and metastatic failure rate was 15.8%. Local pelvic failure rates for stage II and III patients were 10% and 13.6% respectively, but for stage I disease, there was one local failure out of 5 patients, at a rate of 20%. This is probably due to the small number in this subgroup. Complication rate was low with only one patient with grade IV problems, giving a serious complication rate of 1.7% only. Overall actuarial rate in this group was 50.1%. These results are encouraging but further review on achieving adequate follow-up is needed before firm conclusions can be drawn.

Purpose: During a locoregional radiotherapy with curative attempts of lung cancer patients bronchoscopic examinations with biopsies and/or cytologic lavages were repeated to assess the accuracy of limiting the total dose to 60 Gy. In order of the applied dose macroscopic changements of the endoluminal tumor and microscopic elimination should be made out. The correlation between macro- and microscopical regression should allow a statement about reliability of single results. The clinical course and a conventional thoracic X-ray examination seemed to be a to large-meshed screen to evaluate the effect at the end of therapy. The aim was to improve the criterias of success and to adapt and optimize the radiation dose individually., Patients and Methods: The prospective, together with the pneumologists, defined treatment concept included the repetition of bronchoscopic evaluations after the application of 60 Gy and 80 Gy. These radiation doses from 60 Gy up to 80 Gy have been given with a shrinking-field technique to the mediastinum and the primary. In order to record statistically the optical tumor changements we were urged to create a so-called bT-score. The structure of this score was orientated towards the periphery of the tracheobronchial tree., Results: Hundred and forty-four patients with endoscopically and histologically verified bronchogenic carcinomas were treated. On the subjects 215 re-bronchoscopies accomplished with biopsies were performed and allowed to analyze the macro- and microscopical behavior under treatment. A histological/cytological elimination of tumor was achieved after 60 Gy in 35.1%, after 80 Gy in 62.3%. Macroscopically no tumor was visible after 60 Gy in 43.6%, after 80 Gy in 82%. A correlation between identical micro- and macroscopical observations was only seen in 61%, respectively in 71%., Conclusions: The escalation of the radiation dose from 60 Gy up to 80 Gy with shrinked fields could increase the local tumor sterilization rate by 1.8 times from 35.1% to 62.3%. The refining and completion of usually known parameters by endoscopical and histological examinations seems to be an acceptable way to define individual radiation doses. The quality of the performed therapy can be better determined. A predestination of the total dose to a limit of 60 Gy does not ensure a macro- and microscopical elimination of the tumor and may be inferior to an individually adaptation of the dose.

The Berlin-Buch and Heidelberg centres used fast neutron therapy in bronchial carcinomas. The neutron source was a cyclotron in Berlin-Buch/Rossendorf and a d-t generator in Heidelberg. Three hundred twelve patients with inoperable bronchial carcinoma were treated with fast neutron therapy alone or in combination with photons. The results were then compared with those obtained from 594 patients treated only with photons. Altogether, 788 were treated in Berlin-Buch and 188 in Heidelberg. The results suggest that neutron therapy for bronchial carcinoma can be a good alternative in curative and palliative situations in the early stages.

We have experienced eight patients with advanced bronchogenic carcinomas who underwent resectional surgery after receiving preoperative adjuvant chemotherapy and radiotherapy during the period March, 1990, to February, 1992. Four patients were in stage IIIA and four in stage IIIB, of which six had epidermoid carcinomas and two small cell carcinomas. All patients were male with ages ranging from 48 to 73 (mean 56.7) years. The induction chemotherapy for six patients consisted of cisplatin and VP-16 (Etoposide) only, and two patients were given fluorouracil/cyclophosphamide and cyclophosphamide/adriamycin/cisplatin in addition to cisplatin/VP-16, respectively. All patients also received four to six weeks of radiotherapy following chemotherapy and were re-evaluated for the possibility of surgery after four weeks of observation. All patients underwent pneumonectomies. Postoperative histological staging revealed complete responses in two patients, partial responses in three and no response in three. Patients were followed-up for seven to 33 (mean 21.5) months after the diagnosis of lung cancer. Six patients died 1, 2, 3, 10, 14 and 26 months postoperatively and two patients are alive, revealing no evidence of tumor recurrence 24 months postoperatively. Induction therapy may induce a better resectability by the conversion of the lung cancer to a lower clinical stage by the time of surgery.

We present three patients with advanced carcinoma of the uterine cervix treated with full pelvic irradiation followed by surgery 21-37 weeks after the radiation therapy. In two cases chemotherapy was given after radiotherapy due to clinical or radiological residual disease. Postoperative treatment was dependent on histological examination of the surgical specimens. If indicated chemotherapy was started or continued after surgery. No major operative complications were noticed in these three patients in spite of full preoperative pelvic radiation. The information obtained from these operations was valuable in determining the further treatment of the patients. All three patients are clinically disease free at the moment, but longer follow-up will show if this treatment modality can increase survival of advanced carcinoma of the uterine cervix.

Spontaneous pneumothorax following chest irradiation is thought to occur in patients with radiation fibrosis several months or more after the completion of therapy. In the four patients presented herein, spontaneous pneumothorax was seen during or immediately after therapeutic radiation of lung cancer. All patients had bronchoscopic findings of bronchial obstruction by the tumor before treatment and radiographic improvement of atelectasis was observed during therapy. The interval between the improvement of atelectasis and the development of pneumothorax varied by less than three weeks. These common findings suggest that rupture of alveoli or emphysematous bullae and subsequent pneumothorax might be due to overinflation of the affected lung caused by partial bronchial obstruction. We should be aware of the occurrence of spontaneous pneumothorax following partial resolution of total bronchial obstruction.

In this study 201Tl planar scintigraphy and single photon emission computed tomography (SPECT) were performed in 92 patients with solitary lung lesions in order to distinguish malignant versus benign and metastatic masses and to evaluate the radiotherapy response of 15 primary lung carcinomas. Semiquantitative and quantitative analyses were carried out and the results were compared with histopathological diagnosis. The overall sensitivity, specificity and accuracy of semiquantitative analysis were 56, 71 and 58%, and quantitative evaluations were 88.8, 100 and 92%, respectively. Retention indexes (RI) derived from the early and delayed images were 2.9 +/- 1.3 for primary lung carcinomas, -2.78 +/- 0.9 for benign conditions and -2.3 +/- 1.5 for metastatic pulmonary lesions. 201Tl scintigraphy seems to be a sensitive modality for differentiating malignancies from benign conditions since the difference between those two pathologies is significant. However, this procedure has a limited value in distinguishing metastatic pulmonary lesions from benign pathologies, and in tissue characterization of primary lung carcinomas. On the other hand, a good correlation was observed between 201Tl lung scintigraphy and clinical diagnostic examination during postradiotherapy follow-up of inoperable pulmonary neoplasia.

Unlabelled: Lymph node involvement and histologic type are well known and accepted as prognostic factors for bronchial carcinoma. The role of the primary tumor volume has been but rarely examined. However, it is accepted that there is a clear correlation between primary tumor mass and the level of tumor cell dissemination. Therefore primary tumor volume can be a useful prognostic indicator especially for those tumors of which no evidence of metastases can be proved even with CT or MR. In case of 1022 patients, having been received a tumor dose more than 5600 cGys (on the 80% isodose curve), if metastatic including the primary lymph nodes, we examined the correlation between histologic type, lymph node involvement, primary tumor volume and overall survival, response on chest X-ray films, and tumor destruction in autopsy materials, respectively. We found: 1. There was a strong correlation, especially in N0-cases, between primary tumor volume and overall survival, in all histologic types. 2. Small regional metastatic tumors (N1, N2) had a better prognosis than that of great tumors with no metastases (N0), in all histologic types. 3. Small adenocarcinomas and large-cell tumors without lymph node involvement had a better prognosis than that of squamous cell tumors of the same stage. 4. In 222 cases of T2N0-tumors five-year overall survival was 15.3%, in 43 cases of large-cell tumors and adenocarcinomas 29%, respectively., Conclusion: Primary tumor volume is an important prognostic factor and can be easily and objectively evaluated.

From February 1980 to December 1986, 428 cases of cervical cancer in Stage I through IVA were given curative radiation therapy at Chang Gung Memorial Hospital, Taipei. All of them received external irradiation and intracavitary brachytherapy. The degree of tumor regression was assessed immediately before the first intracavitary brachytherapy treatment. Patients were classified at this time as having (a) no gross residual tumor, or (b) gross residual tumor. Factors found to be associated with tumor regression by logistic regression analysis were stage, age and hemoglobin level. Patients with advanced cancer (Stage III, IVA), young age (less than 40 years), and low hemoglobin level (less than 10 g/dl) had a low incidence of no gross residual tumor. Five-year survival rate was 77% in patients with no gross residual tumor and 31% in patients with gross residual tumor (p less than 0.001). This significant difference held true even when one compared these two groups stage for stage; the difference was 77% versus 41% (p less than 0.001) in Stage II and 72% versus 28% (p less than 0.001) in Stage III. The local relapse rate was 59% in the gross residual tumor groups, significantly greater (p less than 0.001) than the 12% found in the no gross residual tumor group. It was concluded that patients whose tumors did not regress after external pelvic irradiation tended to recur after intracavitary brachytherapy, most often locally. This would justify a more aggressive treatment to improve local tumor control in this subset of high risk patients.

The immunocorrective effect of indomethacin in the course of chemoradiation treatment for inoperable lung cancer was established in a group of 117 patients. It manifested itself in an increase in T-lymphocyte level, normalization of their membrane structure and improvement in immunoregulatory function mainly due to a rise in T-helper/inductor level. Blood plasma-circulating immune complex concentration returned to normal. The concomitant administration of indomethacin during chemoradiation therapy improved subjective status of patients and tumor response but failed to increase survival.

Roentgenologic and bronchoscopic examination was performed in 75 patients with central carcinoma of the lung 3-5 months following radiation treatment and every 3-4 months thereafter up to 36 months and longer to establish optimal schedule of those procedures to evaluate response and timely diagnosis recurrence or progression of disease. Complex application of X-ray and endoscopy in lung cancer patients every 3-4 months following radiotherapy assures timely diagnosis of relapse or progression.

Data on 152 cases of lung cancer were studied in an attempt to identify relationship between immunogenetic markers of the HLA system, on the one hand, and histologic pattern of the disease and effectiveness of radiation treatment, on the other. Control group included 200 healthy blood donors. Eight A locus antigens and 16 B locus antigens were studied. In the entire group of patients, HLA-Aw19 antigen was observed less frequently as compared to controls. Similarly infrequent were haplotypes containing the antigen. The occurrence of HLA-B16 antigen was higher in the adenocarcinoma group. Resistance to treatment, particularly, in patients with small-cell histology was associated with the presence of HLA-B8 antigen. Possibility of tissue typing of antigens for diagnosis and prediction of response in lung cancer patients is discussed.

Four established human lung cancer cell lines were exposed to single-dose irradiation. The survival curves of 2 small cell lung carcinomas (SCLC) were characterized by a limited capacity for repair with small and moderate shoulders with extrapolation numbers (n) of 1.05 and 1.60 respectively. Two non-small cell lung carcinoma (NSCLC) cell lines, one squamous cell (SQCLC) and one large cell (LCLC) had large shoulders with n-values of 73 and 15 respectively. The radiosensitivity when measured as D0 did not, however, differ as much from cell line to cell line, with values from 1.22 to 1.65. The surviving fraction after 2 Gy (SF2) was 0.24 and 0.42 respectively in the SCLC cell lines and 0.90 and 0.88 respectively in the NSCLC cell lines. Fractionated irradiation delivered according to 3 different schedules was also investigated. All the schedules delivered a total dose of 10 Gy in 5 days and were applied in 1, 2, and 5 Gy dose fractions respectively. Survival followed the pattern found after single-dose irradiation; it was lowest in the SCLC cell line with the lowest SF and highest in the two NSCLC cell lines. In the SCLC cell lines all schedules were approximately equally efficient. In the LCLC and in the SQCLC cell lines, the 5 Gy schedule killed more cells than the 1 and 2 Gy schedules. The results indicate that the size of the shoulder of the survival curve is essential when choosing the most tumoricidal fractionation schedule.

Between 1983 and 1988 90 patients with bronchial neoplasms needed emergency irradiation to treat superior vena cava syndrome. Pathohistologically verified were 30 cases with squamous cell carcinoma, twelve with adenocarcinoma, five cases with large cell carcinoma, 30 with a small cell carcinoma, and non-differentiated in five others. No histological examination was carried out in eight cases. Im 30 patients distant metastases were evident at the initial diagnosis. The average duration of follow-up was 118 days. The survival course proved to be independent of histopathological grading, previous treatment, and age. Similarly no influence of the fractionation employed could be seen. Very important to the prognosis however, were the stage of disease, the Karnofsky index, and dependent on that, the total reference dose applied. Patients with a Karnofsky index of 50% or lower survived on average only 17 days.

Between September 1980 to December 1984, 85 patients with brain metastases from lung carcinoma were consecutively evaluated and were entered into the first prospective randomized trial. Since January 1985, the second prospective randomized trial was started based on the result of the first trial, i.e., lactate dehydrogenase (LDH) as the most important prognostic factor. We analyzed neurological improvement and survival of 79 patients, who were entered into the second trial until November 1988, compared with the first trial. This preliminary result suggests that LDH may also be an important prognostic factor in the second trial and neurological improvement may depend upon the irradiation dose, therefore we need further investigation in this second trial.

Serum neuron-specific enolase (NSE) has been measured in 28 patients with small cell lung cancer (SCLC) and 90 patients with other forms of lung cancer (NSCLC), i.e., 28 with adenocarcinoma and 62 with squamous cell carcinoma. Increased NSE (greater than 12.0 micrograms/liter) was found in 71.4% of SCLC patients and in 22.2% of NSCLC patients. The predictive value of an increased NSE in identifying SCLC was only 50%, whereas the predictive value of a normal NSE in differentiating SCLC for NSCLC was 91%. Serial studies during chemotherapy of SCLC patients showed that the doubling time of NSE ranged from 7 to 127 days and the mean apparent half-life (AHL) of NSE to be 14 days. AHL values in excess of 20 days suggest that the tumour is not in full remission. We believe that measurement of serum NSE and calculation of the AHL and DT are valuable in identifying the effectiveness of chemotherapy in patients with SCLC.

In 393 patients with invasive squamous cell carcinoma of the uterine cervix stages I to IV the predictive value of the histopathologic classification of Reagan & Wentz (differentiation into cell type) was analysed in relation to 10-year lethality rate. Patients with large cell horn-pearl forming and orthokeratinizing tumours had the poorest, and those with large cell non-keratinizing the best prognosis. Large cell parakeratotic tumours did not differ significantly in prognosis compared with the non-keratinizing cell form. When clinical staging was included the prediction value of the histopathologic classification disappeared except in stage II. From a clinical point of view this additional prognostic information will have little practical consequences.

Results of radiotherapy for lung cancer in the elderly were compared with those in younger patients. A total of 129 patients were treated by radiation therapy with or without chemotherapy. Fifty-six patients (43.4%) were 70 years old or more (elderly group) at the time of treatment, and the remaining 73 patients were below age 70 (younger group). Treatment results in the elderly group were nearly the same as those in the younger group in all stages of the disease. Survival time was longer for patients with performance status (PS) of 0 to 2 than for those with PS 3 or 4 regardless of age (p less than 0.05). The survival time of the elderly group was nearly the same as that of the younger group for squamous cell carcinoma, but somewhat shorter for adenocarcinoma although the difference was not statistically significant. There was no difference in survival between the two groups when they were treated by combined radiation therapy and chemotherapy. Our results suggest that elderly patients can be treated as safely as younger patients by radiotherapy alone or combined radiation therapy and chemotherapy.