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Background: To map anatomic patterns of para-aortic lymph node (PALN) recurrence in cervical cancer patients and validate currently available guidelines on PA clinical target volumes (CTV)., Methods: Cervical cancer patients who developed PALN recurrence were included. The PALNs were classified as left-lateral para-aortic (LPA), aorto-caval (AC), and right para-caval (RPC). Four PA CTVs were contoured for each patient to validate PALN coverage. CTV RTOG was contoured based on the Radiation Therapy Oncology Group guideline. CTV K was contoured as proposed by Keenan et al. CTV M was contoured by expanding symmetrical margins around the aorta and inferior vena cava of 7 mm up to the T12-L1 interspace. CTV new was created by modifying CTV RTOG to obtain better coverage., Results: We identified 92 PALNs in 35 cervical cancer patients. 46.8% of the PALNs were at LPA, 38.0% were at AC, and 15.2% were at RPC areas. CTV RTOG , CTV K , and CTV M covered 87.0%, 88.0%, and 62.0% of all PALNs, respectively. PALN recurrence above the left renal vein was associated with PALN involvement at diagnosis (p = 0.043). Extending upper border to the superior mesenteric artery allowed the CTV new to cover 96.7% of all PALNs and all nodes in 91.4% of patients., Conclusion: CTV RTOG and CTV K encompassed most PALN recurrences. For high-risk patients, such as those having PALN involvement at diagnosis, extending the superior border of CTV from the left renal vein to superior mesenteric artery could be considered., (© 2021. The Author(s).)

Objective: Programmed cell death-ligand 1 (PD-L1) is expressed in tumor cells and has been shown to predict clinical outcomes of several types of malignancies. The aim of this study was to investigate the effects of carbon-ion (C-ion) beam irradiation on PD-L1 expression in human uterine cervical adeno/adenosquamous carcinoma (UCAA) cells and clinical samples and to identify the prognostic factors for outcomes after C-ion radiotherapy (CIRT)., Methods: The effects of C-ion irradiation on PD-L1 expression in human UCAA and cervical squamous cell carcinoma cells were examined by flow cytometry. We examined PD-L1 expression in UCAA biopsy specimens from 33 patients before CIRT started (pre-CIRT) and after 12 Gy (relative biological effectiveness [RBE]) irradiation (post-12Gy-C) in 4 fractions of CIRT to investigate the correlation between PD-L1 status and clinical outcomes., Results: The PD-L1 expression was upregulated by C-ion beam in a dose-dependent manner in HeLa and SiHa cells through phosphorylated Chk1. The overall frequencies of pre-CIRT and post-12Gy-C PD-L1 positivity were 45% (15/33) and 67% (22/33), respectively. The post-12Gy-C PD-L1 expression was significantly elevated compared to the pre-CIRT PD-L1 expression. There was no significant relationship between the pre-CIRT PD-L1 status and clinical outcomes, such as local control (LC), progression-free survival (PFS), and overall survival (OS). However, the post-12Gy-C PD-L1 expression had better correlation with PFS, but not with LC and OS., Conclusion: CIRT can induce PD-L1 expression in UCAA and we propose that PD-L1 expression after starting CIRT may become as a predictive prognostic marker in CIRT for UCAA., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2020. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology.)

Rationale: Leptomeningeal metastasis from cervical adenosquamous carcinoma is extremely rare especially after radiotherapy for vertebral metastasis., Patient Concerns: A 52-year-old woman with International Federation of Gynecology and Obstetrics (FIGO) stage IIB adenosquamous carcinoma of cervix presented with bilateral lower limbs weakening after 2 courses radiotherapy to thoracic vertebral metastases., Diagnoses: Initial spine magnetic resonance imaging (MRI) showed no obvious nerve compression, and radiation myelopathy was suspected by the clinician. Progressive multifocal neurological signs developed one month after completion of spine re-irradiation. She was diagnosed with leptomeningeal metastasis by MRI and cerebrospinal fluid (CSF) study., Interventions: She received whole brain irradiation with a dose of 30 Gy in 10 fractions. Systemic chemotherapy with cisplatin (50 mg/m) and topotecan (0.75 mg/m) was administered sequentially., Outcomes: She died with progressive disease two months after the diagnosis of leptomeningeal metastases., Lessons: Poorly differentiated advanced-stage cervical adenosquamous carcinoma is an aggressive neoplasm with a worse outcome. Leptomeningeal metastasis should be included in the differential diagnosis for patients with multifocal craniospinal neurological signs. A combination of detailed neurological examinations, MRI and CSF study allowed us to establish a correct diagnosis of leptomeningeal metastasis and initiate treatment in a timely manner.

Objective: To compare the survival outcomes of patients with cervical squamous cell carcinoma (SCC) and adenocarcinoma/adenosquamous carcinoma (AC/ASC) among patients with locally advanced cervical cancer that were treated with definitive radiotherapy., Methods: The baseline characteristics and outcome data of patients with locally advanced cervical cancer who were treated with definitive radiotherapy between November 1993 and February 2014 were collected and retrospectively reviewed. A Cox proportional hazards regression model was used to investigate the prognostic significance of AC/ASC histology., Results: The patients with AC/ASC of the cervix exhibited significantly shorter overall survival (OS) (p=0.004) and progression-free survival (PFS) (p=0.002) than the patients with SCC of the cervix. Multivariate analysis showed that AC/ASC histology was an independent negative prognostic factor for PFS. Among the patients who displayed AC/ASC histology, larger tumor size, older age, and incomplete response to radiotherapy were found to be independent prognostic factors. PFS was inversely associated with the number of poor prognostic factors the patients exhibited (the estimated 1-year PFS rates; 100.0%, 77.8%, 42.8%, 0.0% for 0, 1, 2, 3 factors, respectively)., Conclusion: Locally advanced cervical cancer patients with AC/ASC histology experience significantly worse survival outcomes than those with SCC. Further clinical studies are warranted to develop a concurrent chemoradiotherapy (CCRT) protocol that is specifically tailored to locally advanced cervical AC/ASC., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2017. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology)

Purpose: To evaluate the clinical outcomes in patients with International Federation of Gynecology and Obstetrics (FIGO) stage I to IVA squamous cell carcinoma (SCC), adenocarcinoma (AC), and adenosquamous carcinoma (ASC) of the uterine cervix after definitive radiotherapy., Methods: Patients with a primary diagnosis of FIGO stage I-IVA SCC, AC, and ASC of the uterine cervix who had undergone definitive beam radiation with implants or isotopes between 1988 and 2013 were identified using the Surveillance, Epidemiology, and End Results database. Univariate and multivariate Cox regression analyses were performed to analyze the effect of histologic subtype on cause-specific survival (CSS) and overall survival (OS)., Results: A total of 8751 were identified, and 86.0, 10.6, and 3.4 % of patients were SCC, AC, and ASC, respectively. AC patients were more often well differentiated, while more patients were poorly/undifferentiated in ASC subtype. A higher percentage of AC and ASC patients were stage I, and fewer had stage III compared to SCC. Univariate and multivariate Cox analyses showed that histologic subtype was an independent prognostic factor for CSS and OS. SCC subtype had a better CSS and OS compared to AC and ASC subtype. The survival between AC and ASC had no significant difference. The impact of the histologic subtype on CSS and OS was not affected by FIGO stage and the year of diagnosis., Conclusion: AC and ASC subtypes are independent prognostic factors for cervical cancer patients treated with definitive radiotherapy. AC and ASC subtypes are associated with poor survival outcomes than those with SCC.

Background: There are no definitive criteria for identifying which patients with The International Federation of Gynecology and Obstetrics (FIGO) stage IB cervical cancer will benefit from adjuvant therapy after radical hysterectomy. The aims of this study were to clarify the efficacy of adjuvant therapy and assess complications after radical hysterectomy in patients with FIGO stage IB1 cervical cancer with intermediate risk factors., Methods: Between January 2005 and December 2009, the medical records of 75 stage IB1 patients' intermediate risk factors (i.e., tumor size 2-4 cm, lymphovascular involvement, and/or deep stromal invasion >1/2) who underwent radical hysterectomy at six institutions were collected, and these patients were enrolled in this nonrandomized retrospective study. We simplified the criteria of intermediate risk factors as much as possible, as the criteria adopted in some clinical studies are complicated in practice., Results: The patients were grouped according to the receipt of adjuvant therapy as follows: 46 patients, no further treatment; 19 patients, external beam radiation treatment, including 9 patients who received brachytherapy; 5 patients, concurrent chemoradiotherapy (CCRT); and 5 patients, chemotherapy (CT). The clinical outcomes and complications in each group were analyzed. After an average follow-up of 82.6 months (range, 24-135 months), only one patient with all three risk factors who received radiotherapy (RT) experienced recurrence. Excluding this patient, the remaining patients who received RT, CCRT, or CT had two or three risk factors. Lymphedema was significantly more common among patients who received RT or CCRT, whereas the incidence of ileus and ureteral obstruction was not different among the treatment groups. However, an unsutured peritoneum increased the risk of ileus., Conclusions: The findings of this study suggest that RT and CCRT after radical hysterectomy are not beneficial in patients with intermediate risk factors. In particular, RT and CCRT appeared to increase the incidence of lymphedema. A prospective randomized study is needed to verify the findings of this study.

Duplications of the alimentary tract are rare congenital malformations, with the ileum being the most commonly affected site, followed by the oesophagus. Among oesophageal duplications, cystic duplication is the most common and the tubular variety, the rarest. Herein, we report a rare case of tubular oesophageal duplication, complicated by adenosquamous carcinoma at the lower end of the oesophagus, in a 32-year-old man who presented with progressive dysphagia. Although proton pump inhibitors may relieve dysphagia, oesophagectomy and gastric interpositioning should be the first-line treatment for patients with tubular oesophageal duplication, in order to reduce the risk of malignant transformation at the lower end of the oesophagus.

Introduction: Primary mucoepidermoid carcinoma (MEC) of the esophagus is an uncommon neoplasm characterized by a diffuse mixture of squamous and mucus-secreting glandular carcinoma cells. Its biological behavior and response to therapies have not been well studied. Surgical resection is still the primary treatment, but the prognosis is poor. This retrospective study was designed to investigate the clinical characteristics, diagnosis, treatment, and prognosis of primary esophageal MEC., Methods: Clinical data were retrospectively analyzed from 36 patients with pathologically confirmed primary esophageal MEC who underwent transthoracic esophagectomy with lymphadenectomy between January 1991 and June 2010 at the Cancer Hospital of Shantou University Medical College. There were 27 men and 9 women ranging in age from 40 to 78 years (median, 58 years). Twenty-six of the 36 patients were treated with surgery alone. The other 10 were treated with surgery plus postoperative radiotherapy. The Kaplan-Meier and log-rank methods were used to estimate and compare survival rates. Cox's hazard regression model was used to identify prognostic factors, with entry factors of gender, age (≤60 years versus >60 years), length of the primary lesion (≤5 cm versus >5 cm), location of the primary lesion, macroscopic tumor type, tumor cell differentiation, pT, pN, pTNM stage, operation type (radical/palliative), and radiotherapy (yes/no)., Results: The clinical symptoms, radiological and endoscopic features of primary esophageal MEC were similar to those of esophageal squamous cell carcinoma (ESCC). Of the 20 cases who underwent preoperative endoscopic biopsy, 18 cases were misdiagnosed as ESCC and 2 were misdiagnosed as esophageal adenosquamous carcinoma. The mean follow-up duration of this series was 38.8 months (range, 3-142 months). Twenty-two patients had died, 12 were still alive, and 2 were lost to follow-up. The median survival time of the 36 patients was 29.0 months (95% confidence interval = 20.0-38.0), and the 1-, 2-, 3-, and 5-year overall survival rates were 80.6%, 57.1%, 34.4%, and 25.8%, respectively. The 5-year survival rate of 25.8% was lower than 5-year absolute survival rate of 39.2% for ESCC patients who had undergone surgical resection during the same period at our center. For patients who underwent a radical operation, the 5-year survival rate of 32.0% for MEC patients was also lower than that of 41.7% (908/2175) for ESCC patients. In univariate analysis, pN (pN0/pN1-3) (p = 0.003) and operation type (radical/palliative) (p = 0.006) significantly influenced the median survival time of MEC patients. In multivariate analysis, pN (pN0/pN1-3) (p = 0.002) and operation type (radical/palliative) (p = 0.004) were independent prognostic factors., Conclusions: Primary esophageal MEC is a rare disease and prone to be misdiagnosed. Lymph node metastasis and operation are independent prognostic factors. Surgical resection is the primary treatment, but the prognosis is poor.

Aims: This study focused on pelvic recurrence rate and late complications following treatment with high dose rate brachytherapy with a three fractionation scheme., Setting and Design: This retrospective observational study was conducted from 1st November 2003 to 31st March 2005 at a tertiary care centre., Methods and Materials: Women were treated with external beam radiotherapy and three fractions of high dose rate brachytherapy, divided into two broad groups IIB+ IIIA and IIIB+IVA. Duration of follow-up was 2 years and main outcome measures were recurrence and rectal and urinary bladder complications. Results were assessed with the Chi square test and P-values using an alpha level of 0.05 for Type I error., Results: Of the total of 286 women, 72 (25.4%) developed central-regional recurrence. Overall two year pelvic control rate was 74.6%, with values of 78.1% and 72.8% for stages IIB+ IIIA, IIIB+IVA, respectively. Five women developed distant metastasis and 21.5% suffered low grade rectal complications. After two years the prevalence of bladder complications was only 5.4%., Conclusion: Using a three fraction scheme, high dose rate brachytherapy is safe and effective in the management of cervix cancer.

Objective: The current study was a retrospective questionnaire survey of stage IIIb adenocarcinoma of the uterine cervix treated with high-dose-rate intracavitary brachytherapy combined with external beam radiation therapy in Japan aimed to investigate the optimal dose on the basis of the biological effective dose and prognostic factors., Methods: Between 1990 and 2000, 61 patients with stage IIIb adenocarcinoma of the uterine cervix underwent high-dose-rate intracavitary brachytherapy combined with external beam radiation therapy in 19 major hospitals in Japan. This retrospective questionnaire survey was performed by mail including survey charts to be fulfilled by radiation oncologists in these 19 major hospital. Fifty had only adenocarcinoma components and 11 had adenosquamous cell carcinoma components. All patients were treated with high-dose-rate intracavitary brachytherapy combined with external beam radiation therapy. Total biological effective dose (T-BED(10)) was calculated from the sum of the biological effective doses of the external beam radiation therapy and the intracavitary brachytherapy. Thirty-two patients underwent chemotherapy., Results: The 5-year overall survival rate of all patients was 20.2%. Stratified by total biological effective dose, the 5-year overall survival rate was 0% for T-BED(10) <75 Gy, 24.7% for T-BED(10) between 75 and 100 Gy and 0% for T-BED(10) >110 Gy (P = 0.15). Stratified by histopathology, the 5-year overall survival rate was 22.1% for adenocarcinoma and 13.6% for adenosquamous cell carcinoma (P = 0.43). Stratified by chemotherapy, the 5-year overall survival rate was 20.3% in patients who received chemotherapy and 20.4% in patients who did not receive chemotherapy (P = 0.96)., Conclusions: The 5-year overall survival rate of stage IIIb adenocarcinoma of the uterine cervix in this retrospective questionnaire survey was 20.2%. The optimal T-BED(10) and evident prognostic factors were not clear from this questionnaire survey.

Background: There is a need for simple imaging parameters capable of predicting therapeutic outcome., Methods: This retrospective study analysed 50 patients with locally advanced carcinoma of the cervix who underwent dynamic contrast-enhanced MRI before receiving potentially curative radiotherapy. The proportion of enhancing pixels (E(F)) in the whole-tumour volume post-contrast agent injection was calculated and assessed in relation to disease-free survival (DFS)., Results: Tumours with high E(F) had a significantly poorer probability of DFS than those with low E(F) (P=0.011)., Interpretation: E(F) is a simple imaging biomarker that should be studied further in a multi-centre setting.

Purpose: This phase II pilot study was conducted to evaluate the results of a three-modality approach (which included post-chemoradiotherapy surgery) in advanced-stage cervical carcinomas., Patients and Methods: Thirty-six patients underwent either surgery or were put on follow-up after having received radical cervical radiotherapy (RT) combined with radiosensitizing chemoimmunotherapy with irinotecan (CPT-11), interferon (IFN) A2b, and amifostine. The last selection (surgery or follow-up) was based on clinical evaluation (downstaged or not). Feasibility, morbidity, surgical outcome and survival were evaluated., Results: Twenty-six patients had stage IIb and 10 IIIb disease at diagnosis. Sixteen (44%) were clinically downstaged, thus becoming eligible for surgery. Twelve (33%) were operated and the others were put on follow-up. There was no significant increase in treatment-related morbidity of the group of patients receiving three-modality therapy, since only one intraoperative complication had occurred. In 58% of the operated patients, chemoradiotherapy-resistant tumor was found on pathology of the cervical specimens, while 29% of them had lymph nodes infiltrated by the tumor. After a median follow-up of 42.5 months, overall survival (OS) of operated vs. non-operated patients (88 vs. 56%, respectively) show only a trend toward significance (p=0.10). The overall recurrence/metastasis rate was 36.1% and the disease-free survival (DFS) 56% for operated vs. 76% for non-operated patients, respectively (p=0.63)., Conclusion: These results indicate that post-chemoradiotherapy surgery is justified because of the high rate of residual disease found. Morbidity can be effectively limited with proper patient selection. A considerable survival benefit is expected, although this remains to be confirmed with phase III studies.

Objective: In Japan, 5-fluorouracil (5-FU) 400 mg/m(2) on Days 1-5, 8-12, 36-40 and 43-46 with cisplatin (CDDP) 40 mg/m(2) on Days 1, 8, 36 and 43 plus concurrent radiotherapy with 2 weeks planned interruption (60 Gy) was standard for the patients with esophageal cancer. This Phase I trial was designed to determine the maximal tolerated dose (MTD) and dose-limiting toxicity (DLT) of 5-FU on Days 1-4 and 29-32 with CDDP on Days 1 and 29 plus concurrent radiotherapy (50.4 Gy) among the Japanese., Methods: Escalating doses of 5-FU and CDDP were administered with concurrent radiotherapy (50.4 Gy). Treatment was continued until DLT appeared., Results: Twelve patients with previously untreated clinical Stage II/III squamous cell esophageal carcinoma were studied. One of six patients given Level 1 (5-FU 800 mg/m(2) on Days 1-4 and 29-32 with CDDP 75 mg/m(2) on Days 1 and 29) developed a DLT of incomplete protocol treatment due to Grade 3 esophagitis. The MTD was not reached at Level 2 (5-FU 1000 mg/m(2) with CDDP 75 mg/m(2)). The complete response rate was 67% at Level 1 and 100% at Level 2., Conclusions: Dose Level 2 with 50.4 Gy radiotherapy was recommended for Japanese patients.

Objective: To evaluate the patterns of pretreatment diagnostic assessment in uterine cervical cancer patients treated with definitive radiotherapy in Japan., Methods: The Japanese Patterns of Care Study working group conducted a second extramural audit survey of 68 institutions and collected specific information on 631 patients with cervical cancer. All patients were treated with radiotherapy in 1999-2001. Of these, 324 patients treated without surgery were the subjects of this study., Results: International Federation of Gynecology and Obstetrics-prescribed diagnostic procedures were performed at moderate rates in our study cohort. The performance rates of chest X-ray, intravenous urography, cystoscopy, and proctoscopy were 74, 54, 53, and 33%, respectively. Cross sectional imaging studies were frequently performed. Pelvic CT, abdominal CT, and pelvic MRI were performed in 88, 80, and 76%, respectively. Lymphangiography (1%) and surgical evaluation (1%) were rarely done. Only one patient underwent PET scans in this survey period., Conclusions: This study demonstrated the patterns of pretreatment diagnostic assessment in cervical cancer patients treated with definitive radiotherapy in Japan.

Aim: To report the outcome of carcinoma of the uterine cervix patients treated radically by external beam radiotherapy (EBRT) and high-dose-rate (HDR) intracavitary radiotherapy (ICRT)., Materials and Methods: Between January 1997 to December 2001, a total of 550 newly diagnosed cases of carcinoma of the uterine cervix were reported in the department. All cases were staged according to the International Federation of Gynecologists and Oncologists (FIGO) staging system, but for analytical convenience, the staging was limited to stages I, II, III, and IV. Out of the 550 cases, 214 completed radical radiotherapy (EBRT + HDR-ICRT) and were retrospectively analyzed for presence of local residual disease, local recurrence, distant metastases, radiation reactions, and disease-free survival., Results: There were 7 (3.27%), 88 (41.1%), 101 (47.1%), and 18 (8.4%) patients in stage I, II, III, and IV, respectively. The median follow-up time for all patients was 43 months (range: 3-93 months) and for patients who were disease free till the last follow-up it was 59 months (range: 24-93 months). The overall treatment time (OTT) ranged from 52 to 73 days (median 61 days). The 5-year disease-free mean survival rate was 58%, 44%, 33%, and 15%, with 95% confidence interval of 48 to 68, 37 to 51, 24 to 35, and 6 to 24 for stages I, II, III, and IV, respectively. There were 62 (28.97%) cases with local residual disease, 35 (16.3%) developed local recurrence/distant metastases, 17 (7.9%) developed distant metastases, and 9 (4.2%) had local recurrence as well., Discussion and Conclusion: The overall outcome was poor in advanced stage disease, but might be improved by increasing the total dose, decreasing overall duration of treatment, and by adding chemotherapy in patients with disease limited to the pelvis.

Background: A phase I/II study was first conducted for the treatment of stage I non-small cell lung cancer (NSCLC) from 1994 to 1999 to determine the optimal dose. On the basis on the results, a phase II study using a regimen of four fractions during 1 week was performed. The purpose of the present study was to determine the local control and 5-year survival rates., Methods: From December 2000 to November 2003, 79 patients with 80 primary lesions were treated. Using a fixed dose of 52.8 GyE for stage IA NSCLC and 60.0 GyE for stage IB NSCLC in four fractions during 1 week, the primary tumors were irradiated with carbon beams alone. The average age of the patients was 74.8 years. Sixty-two (78.5%) of these patients were medically inoperable. Local control and survival were determined using the Kaplan-Meier method. The data were statistically processed using the log-rank test., Results: All patients were observed for a minimum of 3 years or until death, with a median follow-up time of 38.6 months, ranging from 2.5 to 72.2 months. The local control rate for all patients was 90% (T1: 98%, T2: 80%). The patients' 5-year lung cancer-specific survival rate was 68% (IA: 87%, IB: 42%). The overall survival was 45% (IA: 62%, IB: 25%). Half of the deaths were attributable to intercurrent diseases. No toxic reactions in the lung greater than grade 3 were detected., Conclusion: Carbon ion beam radiotherapy with a regimen of four fractions during 1 week has been proven as a valid alternative to surgery for stage I NSCLC and to offer particular benefits, especially for elderly and inoperable patients.

Purpose: To determine the incidence of the histopathological findings indicative for risk of recurrence in patients with locally advanced cervical cancer (LACC) who were treated with neoadjuvant chemotherapy (NCT) and radiation therapy (RT) before operation., Patients and Methods: Sixty-three patients were included: 45 patients (group 1) underwent external beam RT and then surgical treatment followed by postoperative RT, and 18 (group 2) patients were treated with NCT and surgery followed by postoperative RT. Surgery was class III-V radical hysterectomy with pelvic lymph node dissection (LND), and paraaortic LND at indication. NCT included 2-3 courses of cisplatin, ifosfamide and bleomycin administered at 3-week intervals. In group 1 FIGO stage IIB prevailed (n=29, 64.4%). Forty-four (97.8%) patients had squamous cell carcinoma and 1 (5.6%) adenosquamous carcinoma. In group 2 stage IIB also prevailed (n=13, 72.2%), whereas all 18 (100%) patients had squamous cell carcinoma. The average age in group 1 and 2 was 48.8 years (range 31-69) and 46.3 years (range 32-64), respectively., Results: In group 1 lymph node metastases (LNM) were found in 35.56% of the cases, macroscopically detectable LNM in 15.6%, LNM above the common iliac artery level in 11.1%, multiple LNM (>3 LNM) in 17.8%, parametrial invasion in 4.4%, deep stromal invasion in 31.1%, lymphovascular space invasion (LVSI) in 13.3%, infiltration of canalis cervicalis in 15.6%, infiltration of isthmus uteri in 8.9% and ovarian metastases in 4.4%. In group 2 LNM were found in 38.89% of the patients, macroscopically detectable metastases in 22%, multiple (>3 LNM) LNM in 17%, LNM above the common iliac artery level in 22%, deep stromal invasion in 47%, parametrial infiltration in 24%, LVSI in 12%, tumor infiltration in canalis cervicalis in 12%, and ovarian metastases in 6%., Conclusion: NCT followed by surgical treatment and RT leads to postoperative histological results that are not worse than the standard preoperative RT approach.

Objective: Computed tomographic screening is detecting ever smaller peripheral non-small cell lung cancers. These smaller cancers are amenable to sublobar resection, but sublobar resection is not currently the treatment of choice. This study compared sublobar resection with lobar resection for stage IA non-small cell lung cancers to assess whether sublobar resection is appropriate treatment for certain lesions. The use of adjuvant brachytherapy was also evaluated., Methods: A retrospective multicenter study of 291 patients with T1 N0 disease was done. Outcomes after sublobar resection (n = 124) were compared with those after lobar resection (n = 167). Brachytherapy was used in conjunction with 60 (48%) sublobar resection operations. Analysis based on tumor diameter was performed., Results: There were 137 cancers smaller than 2 cm and 154 cancers ranging from 2 to 3 cm. Patients undergoing sublobar resection were older (68.4 vs 66.1 years, P = .018) with poorer pulmonary function (forced expiratory volume in 1 second of 53.1% vs 78.2%, P = .001). Mean follow-up was 34.5 months. Brachytherapy decreased local recurrence rate significantly among patients undergoing sublobar resection, from 11 (17.2%) to 2 (3.3%). For tumors smaller than 2 cm, there was no difference in survival between sublobar resection and lobar resection groups. For the larger tumors (2-3 cm), median survival was significantly better in the lobar resection group, at 70 versus 44.7 months ( P = .003)., Conclusion: Intraoperative brachytherapy may reduce the local recurrence that is usually reported with sublobar resection. Our experience supports the further investigation of the use of sublobar resection with brachytherapy for peripheral stage IA non-small cell lung cancers smaller than 2 cm.

Background: The aim of this study was to determine the value of routine follow-up for the detection of recurrence in patients treated for cervical cancer., Patients and Methods: From 1986 to 1998, 583 women with stage I and II cervical carcinoma were treated with combined surgery-radiation therapy. After treatment, follow-up was based on clinical examination, a systematic Pap smear and radiography (chest X-ray and abdomino-pelvic ultrasonography)., Results: Forty-five patients had recurrence observed with a delay > or = 6 months following the end of treatment. Thirty-eight patients had symptoms and seven were asymptomatic at the time of their recurrence. Among asymptomatic patients only two recurrences were diagnosed following routine examinations. Survival is similar in asymptomatic and symptomatic recurrent patients., Conclusions: In conclusion, follow-up of patients treated for cervical cancer based on routine Pap smears and systematic radiography does not permit earlier detection of recurrence and does not increase survival.

Purpose: To examine the prognostic value of tumor proliferation measurements in women with carcinoma of the uterine cervix. We report an update of a prospective study focusing on whether pretreatment proliferation parameters are associated with clinical outcome, relative to other established clinical factors., Materials and Methods: One hundred and one patients were recruited into the study from years 1991 to 1999. The LI for in vivo bromodeoxyuridine incorporation by the tumor and the potential doubling time (T(pot)) were determined by flow cytometry (fc). LI and its staining pattern were also assessed by immunohistochemistry (ih) using tissue sections. Apoptosis was assessed histologically using morphological criteria. Patients were treated with definitive radiation therapy., Results: A successful fc measurement for LI-fc and T(pot) was possible in 95 patients (94%). The median/mean LI-fc was 6.6/7.6% (range 1.4-36.1%), and for LI-ih, 10.8/11.5%. To date, 43 patients have died of disease, and the median follow-up for alive patients is 6.2 years (range 1.3-9.3 years). Among 88 patients who completely responded to treatment, 40 patients have relapsed (14 pelvic, 23 distant, and 3 pelvic and distant). In univariate analysis, the significant factors for adverse disease-free survival were large tumor size (P = 0.0001), low hemoglobin (P = 0.001), pelvic lymph node status (P = 0.004), stage (P = 0.013), and overall treatment time (P = 0.0008). In multivariate analysis, only tumor size, pelvic lymph node status, and overall treatment time remained significant for disease-free survival. LI-fc, LI-ih, T(pot), ploidy, pattern of bromodeoxyuridine staining, and apoptosis were not significantly associated with clinical outcome in univariate or multivariate analyses., Conclusions: These mature data indicate that none of the pretreatment proliferation parameters have prognostic significance in the radical radiotherapy of carcinoma of the uterine cervix, despite the significance of overall treatment time for treatment outcome.

Background: The need for radiotherapy (RT) in cancer treatment for the elderly patient is growing. The purpose of this study was to analyze the efficacy and complication rate for radiotherapy, using external-beam irradiation (EBRT) and high dose-rate intracavitary brachytherapy (HDRICB), for patients aged 70 years or older with carcinoma of the uterine cervix., Methods: From September 1992 to December 1997, 295 patients diagnosed with uterine cervical cancer completed RT at the Shin Kong Memorial Hospital and China Medical College Hospital. Two hundred and fifty-eight patients [International Federation of Gynecology and Obstetrics (FIGO) stage distribution: 35 Ib, 26 IIa, 122 IIb, 10 IIIa, 58 IIIb, 7 IVa] who had undergone at least two courses of HDRICB and a minimum of 3 years of follow-up, were evaluated. A retrospective analysis was conducted to compare the outcome of radiation therapy for the 179 patients under 70 years of age (younger group) and the 79 patients aged 70 years or older (older group). The RT consisted of EBRT followed by HDRICB. After a total EBRT dose of 40-45 Gy/20 in 25 fractions, irradiating the whole pelvis over 4-5 weeks, dosage for patients diagnosed as FIGO stage IIb-IVa bilateral parametrial disease was boosted to 54-58 Gy, with central shielding. HDRICB was administered at 1-week intervals using an Ir-192 remote after-loading technique. Ninety-nine patients (38.4%) received three fractions of HDRICB, while 156 patients (60.5%) had four fractions. Total prescribed Point A dosages (EBRT + HDRICB) ranged from 58 to 71.6 Gy (median, 65.6 Gy) for stage IB-IIA, while for larger lesions (stage IIB-IVA) analogous dosages were 59-75.6 Gy (median, 65.6 Gy). Median follow-up durations for the older and younger groups were 56/55 months, respectively., Results: The respective 5-year actuarial survivals (AS) for the older and younger groups were 82/85% for stage Ib, 65/65% for IIa, 61/71% for IIb and 35/59% for IIIa-b. The 5-year cause-specific survivals (CSS) for the older and younger groups were 100/95% for stage Ib, 85/75% for IIa, 78/72% for IIb and 42/61% for IIIa-b. The 5-year pelvic relapse-free survivals (PRFS) for the older and younger groups were 100/100% for stage Ib, 91/93% for IIa, 91/90% for IIb and 67/80% for IIIa-b. The 5-year distant metastasis-free survivals (DMFS) for older and younger groups were 100/100% for stage Ib, 92/88% for IIa, 84/73% for IIb and 55/75% for IIIa-b. There was no statistically significant survival difference on comparing the two groups according to stage. The gross tumor-free ratios after EBRT (NRT) for the older and younger groups were 44.3/24.5% (P = 0.001). The 5-year CSS for the 35 NRT patients was 88% for the older group, while for the 44 patients diagnosed with gross residual tumor after EBRT (GRT) it was 64% (P = 0.001). Twelve (15.0%) of the 79 older patients and 14 (7.8%) of the 179 younger patients developed RTOG grade 3-4 rectal complications (P = 0.12), while seven (8.9%) of the 79 older patients and 10 (5.6%) of the 179 younger patients developed RTOG grade 3-4 small bowel complications (P = 0.34)., Conclusion: Radiation therapy, consisting of a combination of EBRT and three or four fractions of HDRICB, proved to be effective for older patients. Further optimization of treatment policy is essential by changing the HDRICB fractionation strategy, shortening the treatment time and designing combination drug regimens that are both effective and tolerable during radiotherapy.

Unlabelled: In patients with cervical cancer, it is important to estimate prognosis at the time of diagnosis. This study using PET with (18)F-FDG was undertaken to determine whether a simple and fast visual analysis of characteristics of the primary tumor before initiation of treatment could achieve this goal., Methods: Forty-seven patients with cervical cancer who were to be treated by combined radiation therapy and chemotherapy were imaged before beginning treatment. They were then followed for up to 3 y for evidence of recurrence or death. Images of the chest, abdomen, and pelvis were obtained 40-90 min after administration of 370-555 MBq (10-15 mCi) (18)F-FDG. Three observers then independently graded the primary tumor for size (0 = small, 1 = moderate, 2 = large), shape (0 = spherical, 1 = nonspherical), heterogeneity of uptake (0 = none, 1 = moderate, 2 = marked), and presence of lymph nodes (0 = none, 1 = pelvic, 2 = paraaortic, 3 = distant). The scores were summed to achieve a total score. A statistical calculation demonstrated that a score cutoff of 4 best separated patients with a good prognosis from patients with a bad prognosis. Kaplan-Meier analysis was used to compute progression-free survival and overall survival. Evaluation of lymph nodes alone was compared with the grading of tumor characteristics., Results: Observers 1 and 2 scored 26 patients as having a good prognosis and 21 as having a bad prognosis. Observer 3 scored 30 and 17, respectively, a statistically insignificant difference. Survival curves were almost identical for the 3 observers. For progression-free survival, approximately 12% of patients with a good score had disease recurrence whereas approximately 75% with a bad score had disease recurrence. For overall survival, approximately 10% (good) and 80% (bad) died. Evaluation of lymph nodes also separated the groups, but not as well as did visual analysis alone. The combination of the 2 was only slightly superior to visual assessment alone., Conclusion: A simple, rapid, and highly reproducible system is described for visual grading of characteristics of the primary tumor in patients with cervical cancer at the time of diagnosis. This approach separates patients with a poor prognosis from those who will do well, thus providing a new tool for accurate estimation of prognosis.

Background: Randomized studies comparing induction chemotherapy followed by surgical resection with radiation alone found that the neoadjuvant approach produces better results. So far, this latter modality has not been compared with standard concomitant chemoradiation. The objective of this report was to compare the results of two consecutive phase II studies: neoadjuvant chemotherapy followed by surgery or chemoradiation for the unresectable cases versus standard cisplatin-based chemoradiation., Patients and Methods: From February 1999 to July 1999, 41 patients with cervical carcinoma, stages IB2-IIIB, were treated with neoadjuvant chemotherapy. Treatment consisted of three 21-day courses of cisplatin 100 mg/m(2) on day 1 and gemcitabine 1000 mg/m(2) on days 1 and 8, followed by either surgery or concomitant chemoradiation for the non-operable cases. From August 1999 to December 1999, an equal number of patients having comparable clinicopathological characteristics were treated with six weekly courses of cisplatin 40 mg/m(2) during standard pelvic radiation., Results: A total of 82 patients were analyzed. Both groups were similar with regard to age, histology, International Federation of Gynecology and Obstetrics (FIGO) stage, tumor size, pretreatment hemoglobin levels, parametrial infiltration and performance status. In the neoadjuvant arm the overall response rate to induction chemotherapy was 95% (95% confidence interval 88% to 100%). Twenty-three patients had surgery and 14 underwent chemoradiation. In the definitive chemoradiation study, 38 patients completed treatment, the median number of cisplatin courses was six for a dose intensity of 33 mg/m(2)/week. Doses to points A and B were 85 Gy (range 68-95) and 55 Gy (range 51-65), respectively. Chemoradiation was delivered in 44.6 (range 28-113) days. Complete response rates after all treatment were similar: 97% and 87% in the neoadjuvant and chemoradiation groups, respectively. At a median follow-up of 28 (range 2-33) and 24 (range 3-30) months, respectively, there were no differences in overall survival. To date, 15 and 13 patients in the neoadjuvant and chemoradiation groups, respectively, have died of disease (P = 0.8567)., Conclusions: The results of this non-randomized comparison suggest that induction chemotherapy followed by surgery or chemoradiation is at least as effective in terms of response and survival as standard cisplatin-based chemoradiation. A randomized study is needed to confirm these findings.

Endometrial glassy cell carcinoma (GCC) is a rare neoplasm, with 11 cases reported in the literature. Although GCC is considered to be a poorly differentiated variant of adenosquamous carcinoma, its real nature is still debatable. We report a case of GCC of the endometrium in a 60-year-old woman and review the literature. The patient presented with vaginal bleeding, and pelvic computed tomographic scan showed a polypoid lesion in the uterine fundus. Histologically, the tumor showed 2 components: a moderately differentiated adenocarcinoma with extensive areas of squamous metaplasia (adenoacanthoma) and a GCC. The clinical stage of the patient's disease was IB as classified by the International Federation of Gynecology and Obstetrics. She was treated by a total abdominal hysterectomy, bilateral salpingo-oophorectomy, and pelvic radiation therapy. The patient was still alive and free of disease at 5 years of follow-up.

Although neutropenia increases the risk of life-threatening infections, bacterial meningitis is rarely encountered as a complication during cancer chemotherapy in adults with a solid tumor. A 66-year-old male with adenosquamous carcinoma of the lung, cT2N3M0, stage IIIB, was enrolled in a phase I trial of chemoradiotherapy and treated with cisplatin 80 mg/m2 (122 mg/ body) on day 1, vinorelbine 20 mg/m2 (32 mg/body) on days 1 and 8 and thoracic radiotherapy 30 Gy/15 fractions, beginning on day 2, with dexamethasone administered for antiemesis at a dose of 16 mg on day 1, 8 mg on days 2 and 3, 4 mg on day 4 and 2 mg on day 5. The patient developed headache and fever on day 6 of the second cycle of the treatment and bacterial meningitis was diagnosed based on the findings of consciousness disturbance, an elevated peripheral blood leukocyte count and numerous leukocytes in the cerebrospinal fluid. In spite of the doctor's delay in establishing the exact diagnosis, the bacterial meningitis in this case was successfully treated with intensive antibiotic therapy. This life-threatening complication, equivalent to a grade 4 non-hematological adverse reaction, was not counted as dose-limiting toxicity in the current phase I trial, because there are only a few reports of bacterial meningitis associated with cancer chemotherapy and it developed in this case without any associated decrease in the peripheral blood leukocyte count.

The aim of the study was to evaluate VEGF expression in tumour biopsies as a prognostic factor for radiotherapy outcome in advanced carcinoma of the cervix. A retrospective study was carried out on 100 patients. Pre-treatment tumour VEGF expression was examined immunohistochemically in formalin-fixed, paraffin-embedded biopsies using a widely available commercial antibody. A semi-quantitative analysis was made using a scoring system of 0, 1, 2, and 3, for increasing intensity of staining. High VEGF expression was associated with a poor prognosis. A univariate log rank analysis found a significant relationship with overall survival (P = 0.0008) and metastasis-free survival (P = 0.0062), but not local control (P = 0.23). There was no correlation between VEGF expression and disease stage, tumour differentiation, patient age, or tumour radiosensitivity (SF2). In a Cox multivariate analysis of survival VEGF expression was the most significant independent prognostic factor (P = 0.001). After allowing for VEGF only SF2 was a significant prognostic factor (P = 0.003). In conclusion, immunohistochemical analysis of VEGF expression is a highly significant and independent prognostic indicator of overall and metastasis-free survival for patients treated with radiotherapy for advanced carcinoma of the cervix. It is also a rapid and easy method that could be used in the clinical setting, to identify patients at high risk of failure with conventional radiotherapy who may benefit from novel approaches or chemoradiotherapy., (Copyright 2000 Cancer Research Campaign.)

Objective: This retrospective study evaluates probability of survival and mode of recurrence in patients with a microscopically positive bronchial resection margin following resection for primary bronchogenic carcinoma, as well as influence of radiotherapy on survival., Methods: From January 1986 to July 1997, 40 patients had a microscopically positive bronchial resection margin following a macroscopically complete resection (17 lobectomies, three bilobectomies, four sleeve-lobectomies, and 16 pneumonectomies). Tissue diagnosis was squamous cell carcinoma in 32 patients, adenocarcinoma in four, adenosquamous carcinoma in two and neuroendocrine carcinoma in two. Lymph node status was N0 in 14 patients, N1 in 10, and N2 in 16. The bronchial margin contained carcinoma in situ in 20 patients, invasive mucosal carcinoma in five, and peribronchial infiltration in 15. All patients except the three most recent underwent adjuvant radiation therapy., Results: At the conclusion of the study (January 31st, 1999), 30 patients had died: two with post-operative complications, 17 with progressive disease, ten without relation to cancer, and one under undefined circumstances. Six of 10 unrelated deaths were interpreted as respiratory complications of radiotherapy. Recurrent disease appeared in 24 patients (60%). Nineteen had progression of initial disease (47.5%): metastatic spread in 12 (30%), isolated local recurrence in four (10%), and combined local recurrence and metastases in three (7.5%). Five patients developed metachronous cancer, with bronchial location in four (10%) and laryngeal in one (2.5%). 5-year survival (Kaplan-Meier) in 20 patients with carcinoma in situ was 38.7+/-13.7% (median 31 months), but rose to 55.0+/-16. 6% when excluding seven deaths not related to cancer (five of whom were secondary to radiotherapy) (chi(2)=3.080; P=0.0792). Survival in 13 patients classified N0 was 51.3+/-16.3% (median 61 months), and 71.1+/-18.0% following exclusion of unrelated deaths (chi(2)=3. 939; P=0.0472). Adverse prognosis of peribronchial infiltration was correlated to a positive N status (13 N2 and 2 N1), 5-year survival being 20.0+/-10.3% (median: 18 months)., Conclusions: Prognosis of peribronchial infiltration is similar to N2 disease. In situ carcinoma does not influence survival per se. Local control of disease is probably in part due to radiotherapy. However, the high prevalence of unrelated late deaths suggests an adverse impact of radiotherapy on survival.

Background: Tumor control and late complication rates of irregularly shaped four-field whole pelvic radiotherapy using CT simulation were compared with those of whole pelvic radiotherapy using parallel-opposed fields in a non-randomized study., Methods: From 1986 to 1996, 74 patients who underwent surgery for clinical stage I, II or III squamous or adenosquamous cell carcinoma of the uterine cervix were treated with postoperative radiotherapy consisting of 50 Gy in 25 fractions in 6 weeks. Thirty-four patients were treated with an irregularly shaped four-field technique following computed tomography (CT) simulation using beam's eye view and three-dimensional treatment planning and lead blocks. Forty patients received the conventional two-field technique, with CT simulation in 13 patients and X-ray simulation in 27 patients. There was no significant difference in patients' characteristics between the two groups., Results: There was no statistical difference in survival, relapse-free survival or pelvic control rate between the two-field and irregularly shaped four-field groups with a mean follow-up period of 60 months. The actual 5-year pelvic control rate was 94% for the two-field technique and 100% for the irregularly shaped four-field technique. The incidence of grade II-III bowel complications in the irregularly shaped technique group (2.9%, 1/34) was significantly lower than that in the two-field technique group (17.5%, 7/40) (p < 0.05). The actual 5-year complication rates of grade II leg edema were 28.6 and 3.1% for the two-field technique and irregularly shaped four-field technique groups, respectively (p = 0.0123)., Conclusions: Irregularly shaped four-field post-operative pelvic radiotherapy using CT simulation appears to be as effective as parallel-opposed whole pelvic radiotherapy with a lower incidence of bowel complication and chronic leg edema.

We assessed the therapeutic significance of systematic aortic and pelvic lymphadenectomy followed by adjuvant therapy in node-positive endometrial carcinoma. Among 173 stage I-III patients, 30 (17%) had positive nodes: ten in the pelvic region alone (group P) and 20 in the aortic region alone or in both regions (group A). The adjuvant therapy was administered as follows: subjects in group P received 50 Gy pelvic radiation, including three post-surgical T3 (pT3) patients who received either one or three cycles of cisplatin-based chemotherapy before radiation. Subjects in group A were given three cycles of chemotherapy followed by 50 Gy pelvic and 50 Gy extended field periaortic radiation using a four-field or conformational technique. Five-year survival was 95% for 143 patients with negative nodes and 84% for 30 patients with positive nodes (100% for group P and 75% for group A). In group A, 5-year survival was 38% for eight patients with both pT3 and histology other than endometrioid type G1, and 91% for the remaining 12 patients. Either way, both group P and group A patients had a better prognosis than previously reported. In summary, aortic and pelvic lymphadenectomy and subsequent chemotherapy and radiation therapy based on node status seem to improve the survival of endometrial cancer patients with positive nodes.