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Background: At the first interim analysis of the phase 3 ENGOT-cx11/GOG-3047/KEYNOTE-A18 study, the addition of pembrolizumab to chemoradiotherapy provided a statistically significant and clinically meaningful improvement in progression-free survival in patients with locally advanced cervical cancer. We report the overall survival results from the second interim analysis of this study., Methods: Eligible patients with newly diagnosed, high-risk (FIGO 2014 stage IB2-IIB with node-positive disease or stage III-IVA regardless of nodal status), locally advanced, histologically confirmed, squamous cell carcinoma, adenocarcinoma, or adenosquamous cervical cancer were randomly assigned 1:1 to receive five cycles of pembrolizumab (200 mg) or placebo every 3 weeks with concurrent chemoradiotherapy, followed by 15 cycles of pembrolizumab (400 mg) or placebo every 6 weeks. Pembrolizumab or placebo and cisplatin were administered intravenously. Patients were stratified at randomisation by planned external beam radiotherapy type (intensity-modulated radiotherapy [IMRT] or volumetric-modulated arc therapy [VMAT] vs non-IMRT or non-VMAT), cervical cancer stage at screening (FIGO 2014 stage IB2-IIB node positive vs III-IVA), and planned total radiotherapy (external beam radiotherapy plus brachytherapy) dose (<70 Gy vs ≥70 Gy [equivalent dose of 2 Gy]). Primary endpoints were progression-free survival per RECIST 1.1 by investigator or by histopathological confirmation of suspected disease progression and overall survival defined as the time from randomisation to death due to any cause. Safety was a secondary endpoint., Findings: Between June 9, 2020, and Dec 15, 2022, 1060 patients at 176 sites in 30 countries across Asia, Australia, Europe, North America, and South America were randomly assigned to treatment, with 529 patients in the pembrolizumab-chemoradiotherapy group and 531 patients in the placebo-chemoradiotherapy group. At the protocol-specified second interim analysis (data cutoff Jan 8, 2024), median follow-up was 29·9 months (IQR 23·3-34·3). Median overall survival was not reached in either group; 36-month overall survival was 82·6% (95% CI 78·4-86·1) in the pembrolizumab-chemoradiotherapy group and 74·8% (70·1-78·8) in the placebo-chemoradiotherapy group. The hazard ratio for death was 0·67 (95% CI 0·50-0·90; p=0·0040), meeting the protocol-specified primary objective. 413 (78%) of 528 patients in the pembrolizumab-chemoradiotherapy group and 371 (70%) of 530 in the placebo-chemoradiotherapy group had a grade 3 or higher adverse event, with anaemia, white blood cell count decreased, and neutrophil count decreased being the most common adverse events. Potentially immune-mediated adverse events occurred in 206 (39%) of 528 patients in the pembrolizumab-chemoradiotherapy group and 90 (17%) of 530 patients in the placebo-chemoradiotherapy group. This study is registered with ClinicalTrials.gov, NCT04221945., Interpretation: Pembrolizumab plus chemoradiotherapy significantly improved overall survival in patients with locally advanced cervical cancer These data, together with results from the first interim analysis, support this immuno-chemoradiotherapy strategy as a new standard of care for this population., Funding: Merck Sharp & Dohme, a subsidiary of Merck & Co., Competing Interests: Declaration of interests DL, YX, KH, GS, ML, PR-E, AA, JC, LR, AJPdSG, FCM, LH, HA, J-YL, VS, FZ, LG, JS, ET, KL, NC, C-LC, MB, HZ, AO, MC, EP, TU, SP, and LRD received funding to their institutions from Merck Sharp & Dohme, a subsidiary of Merck & Co, Rahway, NJ, USA (MSD) to support the study. DL reports grants or contracts from AstraZeneca, Clovis Oncology, Pharma&, Genmab, GSK, Immunogen, MSD, Pharmamar, Novartis, Seagen, Alkermes, Incyte, Roche, and Corcept; consulting fees from AstraZeneca, Corcept, Clovis Oncology, Daiichi Sankyo, Genmab, GSK, Immunogen, MSD, Novartis, Oncoinvest, Novocure, Seagen, and Sutro; speaker fees from AstraZeneca, Corcept, Genmab, GSK, Immunogen, MSD, and Seagen; travel grants from AstraZeneca, Menarini, GSK, and MSD; advisory board participation for AstraZeneca, Corcept, Clovis Oncology, Daiichi Sankyo, Genmab, GSK, Immunogen, MSD, Oncoinvest, Novocure, Seagen, and Sutro; and leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid, for GCIG, MITO, and ENGOT. YX reports study funding, paid to the Peking Union Medical College Hospital, and support for attending meetings or travel from MSD. KH reports research contracts from Daiichi Sankyo, Eisai, MSD, and Takeda; advisory board fees from Chugai, Eisai, Takeda, MSD, Roche, Genmab, Sanofi, GSK, and Zymeworks; honoraria from Daiichi Sankyo, AstraZeneca, Chugai, Eisai, Genmab, MSD, Takeda, Sanofi, Kyowa Kirin, Kaken, and GSK; and travel support from Regeneron and Seagen. GS reports consulting fees from AstraZeneca, MSD, Coviden AG (a Medtronic company), Johnson & Johnson, and TESARO Bio Italy; and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or education events from Baxter Healthcare, Olympus Europa, Intuitive Surgical, GSK, and Clovis Oncology Italy. ML reports payment for expert testimony from MSD, support for attending meetings or travel from MSD and AstraZeneca; and other financial or non-financial interests from MSD, AstraZeneca, and Roche. PR-E reports honoraria for educational events from MSD, AstraZeneca, Novartis, Asofarma, Pfizer, and Roche; support for attending ESMO and ASCO meetings from AstraZeneca, Pfizer, and Asofarma; and honoraria for advisory boards from MSD, Roche, AstraZeneca, Asofarma, BMS and Novartis. LR reports medical writing support from Merck, institutional grants from Merck, Zentalis, Karyopharn, GOG Foundation, Regeneron, ImmunoGen, Acrivon, CanariaBio, Corcept Therapeutics, and Seagen; consulting fees from AstraZeneca, Merck, GSK, Genmab, Seagen, GOG Foundation, Zentalis, ImmunoGen, Semline, Eisai, Caris, Nykode, and Clovis; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Seagen and Genmab; and leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid, from GOG Foundation. AJPdSG reports consulting fees and payment for expert testimony from Bayer, Astellas, and Janssen; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events for expert testimony from Astellas, AstraZeneca, Bayer, and Janssen; and participation on a data safety monitoring board or advisory board for Astellas, Bayer, and Janssen. FCM reports honoraria for presentations from MSD and BMS; support for attending meetings or travel from AstraZeneca and MSD; and advisory board participation from Janssen and MSD. J-YL reports support for the present manuscript from MSD; grants or contracts from Advenchen, Ascendis Pharma, Alkermes, AstraZeneca, Beigene, BergenBio, BMS, CanariaBio, Corcept, Cellid, CKD, Clovis Oncology, Eisai, Genmab, Genemedicine, GII, GSK, ImmunoGen, Janssen, Kelun, Merck, Mersana, MSD, Novartis, Onconic Therapeutics, ONO, Regeneron, Roche, Seagen, Sutro, Synthon, and Takeda; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca, Janssen, MSD, Roche, Takeda, and ONO; and leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid, for AstraZeneca, CanariaBio, Genmab, GII, ImmunoGen, Seagen, Merck, Sutro, Regeneron, and MSD. FZ reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events, consulting fees, support for attending meetings or travel, and data safety monitoring board and advisory board participation for AstraZeneca, Daiichi, Eli-Lilly, Merck, Novartis, MSD, Pfizer, Genesis-Pharma, and Roche. LG reports institutional grants from IMV, Pfizer, Sutro Bio, Pharma, Merck Sharpe Dohme, Corcept Therapeutics, ImmunoGen, Shattuck Labs, Roche, Tesaro, K-Group, Beta Inc., GOG Foundation, GSK, AstraZeneca, OncoQuest Pharmaceuticals, Novocure, Alkermes, Espersas, and Mersana; consulting fees from Merck and GSK; payment or honoraria for lectures and presentations from Merck and GSK; support for attending meetings or travel from GSK, Merck, EndomERA, and Zentalis; and participation on advisory board meetings for GSK, Merck, Eisai, Novocure, Kora Health, Corcept, ImmunoGen, Canariabio, and Repare Therapeutics. JS reports grants or contracts from Roche, MSD, GSK, Tesaro, AstraZeneca, Eisai, Merck, and Novocure; consulting fees from Immunogen, Incyte, GSK, AstraZeneca, Clovis, Novocure, MSD, Eisai, and Merck; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Immunogen, Incyte, GSK, AstraZeneca, Clovis, Novocure, BMS, Eisai, and Novartis; support for attending meetings or travel from GSK, Astra Zeneca, Roche, Novocure, Immunogen, Incyte, MSD, and Eisei; participation on a data safety monitoring board or advisory board for Immunogen, Incyte, GSK, AstraZeneca, Clovis, Novocure, Bristol Myers Squibb, MSD, Merck, Bayer, and PharmaMar; leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid, for ENGAGE, ESGO, ASCO, ESGO, GCIG, Deutsche Stiftung Eierstockkrebs, and AGO; and medical writing assistance from MSD. ET reports honoraria for presentations and meeting travel support from Elektra. KL reports study funding from MSD; grants or contracts from GSK; lecture honoraria from Eisai and AstraZeneca; participation on a data safety monitoring board for Karyopharm; participation on an advisory board for Eisai, MSD, Nykode, AstraZeneca, and GSK; and serving as deputy medical director for the Nordic Society of Gynecological Oncology Clinical Trial Unit. NC reports institutional grants from AstraZeneca and Roche; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from GSK and MSD; payment for participation on a data safety monitoring board or advisory board for AstraZeneca, Clovis Oncology, Eisai, GSK, ImmunoGen, Mersana, MSD, Merck, Nuvation Bio, Onxerna, Pfizer, PharmaMar, Pieris, Roche, and Novocure; and non-remunerated leadership role as Chair of the Alleanza Contro il Tumore Ovarico Scientific Committee. MB reports honoraria for lectures and educational events from Roche, AstraZeneca, and GSK; and support for attending meetings from Roche, AstraZeneca, and Viatris. AO reports consulting fees from Agenus, AstraZeneca, Clovis Oncology, Corcept Therapeutics, Deciphera Pharmaceuticals, Daïichi Sankyo, Debiopharm International, Eisai, Exelisis, F. Hoffmann-La Roche, Genmab, GSK, ImmunoGen, Itheos, MSD, Mersana Therapeutics, Myriad Genetics, Novocure, OncoXerna Therapeutics, PharmaMar, Regeneron, Sattucklabs, Seagen–Pfizer, Sutro Biopharma, TORL Therapuetics, Zentalis, and Zymeworks; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from NSGO, Peerview, Peervoice, Medscape, Asociación Colombiada de Ginecológos Oncólogos, ESO, AstraZeneca, and GSK; support for attending meetings or travel from AstraZeneca, PharmaMar, and Roche; participation on a data safety monitoring board or advisory board from Agenus, AstraZeneca, Clovis Oncology, Corcept Therapeutics, Deciphera Pharmaceuticals, Daïichi Sankyo, Debiopharm International, Eisai, Exelisis, F Hoffmann-La Roche, Genmab, GSK, ImmunoGen, Itheos, MSD, Mersana Therapeutics, Myriad Genetics, Novocure, OncoXerna Therapeutics, PharmaMar, Regeneron, Sattucklabs, Seagen–Pfizer, Sutro Biopharma, TORL Therapuetics, Zentalis, and Zymeworks; leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid, for Gynecologic Cancer Intergroup and European Society for Medical Oncology; and other financial or non-financial interests in Gynecologic Cancer Intergroup, European Society for Medical Oncology, American Society of Clinical Oncology, Spanish Society of Medical Oncology, and GOG Foundation. EP reports provision of study material from MSD; honoraria for lectures, presentations, and educational events from MSD, Roche, GSK, and AstraZeneca; and receipt of investigational drug for study treatment from MSD. PL, KY, ST, and SMK are current or former full-time employees of MSD and hold stock or restricted stock units in the company. SP reports research funding from Roche, MSD, GSK, Pfizer, and AstraZeneca; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca, MSD, Roche, Pfizer, Novartis, and GSK; and participation on a Data Safety Monitoring Board or Advisory Board for GSK, MSD, Eisai, Biontech, and AstraZeneca. LRD reports institutional grants from Merck, Genentech, Roche, AbbVie, Acrivon, Advaxis, Aduro BioTech, Alkermes, Blueprint, Constellation, Eisai, GSK, Novartis, Immunogen, Inovio, Iovance, Karyopharm, KSQ Therapeutics, Lycera, Morab, MorphoTek, Naveris, Nurix, OncoQuest, Pfizer, Syndax, Tesaro, and Zentalis; royalties or licenses from UpToDate, Wiley, and ASCO; editing for ASCO Connection; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Advance Medical, CEA Group, and Clinical Care Options; participation on a data safety monitoring board for Innovia and Aegenus (payment to institution); and roles as Secretary Treasurer for SGO (unpaid) and on the Editorial Board of the British Journal of Obstetrics and Gynaecology., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

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: To elucidate tumor mutation profiles associated with outcomes of uterine cervical cancer (UCC) patients treated with definitive radiotherapy., Methods: Ninety-eight patients with newly diagnosed and pathologically confirmed UCC (82 squamous cell carcinomas, 12 adenocarcinomas, and four adenosquamous carcinomas) who were treated with definitive radiotherapy were analyzed. DNA was extracted from pre-treatment tumor biopsy specimens. The exons of 409 cancer-related genes were sequenced using a next-generation sequencer. Genetic mutations were identified and analyzed for correlations with clinical outcome., Results: Recurrent mutations were observed in PIK3CA (35.7%), ARID1A (25.5%), NOTCH1 (19.4%), FGFR3 (16.3%), FBXW7 (19.4%), TP53 (13.3%), EP300 (12.2%), and FGFR4 (10.2%). The prevalence of mutations in FGFR family genes (i.e., FGFR1-4) was almost as high (24.5%) as that in PIK3CA and ARID1A, both of which are well-studied drivers of UCC. Fifty-five percent (21 of 38) of the identified FGFR mutations were located in the FGFR protein tyrosine kinase domain. Five-year progression-free survival (PFS) rates for FGFR mutation-positive patients (n = 24) were significantly worse than those for FGFR mutation-negative patients (n = 74) (43.9% vs. 68.5%, respectively; P = 0.010). Multivariate analysis identified FGFR mutations as significant predictors of worse 5 year PFS (P = 0.005), independent of clinicopathological variables., Conclusions: FGFR mutations are associated with worse PFS in UCC patients treated with definitive radiotherapy. These results warrant further validation in prospective studies., Competing Interests: Declaration of Competing Interest Yoshiyuki Suzuki holds a research grant from Chugai Pharmaceutical Co., Ltd. for unrelated work, as well as receiving consulting fees from Kyowa Kirin Co., Ltd. Yuya Yoshimoto has received lecture fees from AstraZeneca K.K. Yasushi Sasaki has received research grants from Ono Pharmaceutical Co., Ltd., Daiichi Sankyo Company Limited, Merck Sharp & Dohme, Yuasa Kinenkai, and the Ono Cancer Research Fund for unrelated research, as well as lecture fees from Chugai Pharmaceutical Co., Ltd., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

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.)

Purpose: As a small-molecule tyrosine kinase inhibitor of vascular endothelial growth factor receptor 2 (VEGFR2), apatinib has shown a survival benefit in multiple solid tumors. This study aims to evaluate the efficacy and safety of apatinib in patients with metastatic, recurrent cervical cancer after failure of radiotherapy and first-line chemotherapy., Methods: A total of 42 patients between June 2018 and March 2019 were involved in this study. All patients orally received apatinib once daily in a 4-week cycle until disease progression or adverse events that prohibit further therapy. The primary endpoint was progression-free survival (PFS), the secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), health-related quality of life (HRQoL) and adverse events., Results: During a median follow-up of 13 months, 8 patients achieved a partial response and 24 cases achieved stable disease. None of them reported a complete response. The ORR and DCR were 19.0 and 76.2%, respectively. The median PFS was 6.0 months (95% CI 4.9-7.1), and the median OS was 12.0 months (95% CI 10.1-13.9). The global health score/HRQoL improved significantly following 3-cycle treatment (50.4 ± 12.5 vs. 60.1 ± 11.8; p < 0.01). The most frequent grade 3-4 adverse events were hand-foot syndrome, hypertension and fatigue., Conclusion: Apatinib should be an effective and tolerable treatment option for patients with metastatic, recurrent cervical cancer after failure of radiotherapy and first-line chemotherapy., (© 2020 S. Karger AG, Basel.)

Background: The aim of this study was to evaluate the effects of treatment with both three-dimensional radiotherapy (3DRT) and weekly 40-mg/m 2 cisplatin on postoperative uterine cervical cancer patients with high-risk prognostic factors., Methods: We conducted a retrospective multi-institutional chart review of postoperative uterine cervical cancer patients with high-risk prognostic factors who had been treated with both 3DRT and weekly 40-mg/m 2 cisplatin from 2007 to 2012. Each participating hospital provided detailed information regarding patient characteristics, treatment outcomes, and treatment complications., Results: The eligible 96 patients were analyzed. The median follow-up period was 61 months. The 3-year relapse-free survival, overall survival (OS), and locoregional relapse-free survival (LRFS) rates were 76%, 90%, and 88%, respectively. In multivariate analysis, the histological finding of either adenocarcinoma or adenosquamous carcinoma was a significant risk factor for both OS and LRFS. The percentage of patients with grade ≥ 3 acute hematologic toxicity, acute lower gastrointestinal toxicity (GIT), and late lower GIT were 45%, 19%, and 17%, respectively., Conclusions: The outcomes of concurrent chemoradiotherapy (CCRT) using weekly 40-mg/m 2 cisplatin are similar to those in the previous studies that used several chemotherapy regimens. However, postoperative CCRT using 3DRT had a high level of late GIT.

Purpose: Metaplastic breast cancer (MBC) is a rare, aggressive form of breast cancer with limited data to guide management. This study of a large, contemporary US database described national practice patterns and addressed the impact of radiotherapy (RT) on survival., Methods: The National Cancer Data Base was queried (2004-2013) for women with non-metastatic MBC. Multivariable logistic regression ascertained factors associated with RT administration. Kaplan-Meier analysis evaluated overall survival (OS) between patients treated with either lumpectomy or mastectomy with or without RT, while substratifying patients into pT1-2N0 and pT3-4/N+ subcohorts. Cox proportional hazards modeling determined variables associated with OS., Results: Of 5211 total patients, 447 (9%) had lumpectomy alone, 1831 (35%) had post-lumpectomy RT, 2020 (39%) had mastectomy alone, and 913 (18%) had post-mastectomy RT (PMRT). Most patients underwent chemotherapy (79%), and mastectomy was the most common surgical approach (56%). RT delivery was impacted by many factors, including higher nodal disease (p < 0.001), but not T classification or estrogen receptor status (p > 0.05 for both). Post-lumpectomy RT was associated with higher OS in both the pT1-2N0 and pT3-4/N+ subsets (p < 0.001 for both), while PMRT was associated with OS benefits in pT3-4/N+ cases (p < 0.001), but not in pT1-2N0 cases (p = 0.259)., Conclusions: In the largest study to date evaluating MBC, practice patterns of surgery, systemic therapy, and RT are described. The addition of RT in the post-lumpectomy setting was associated with higher OS, in addition to pT3-4/N+ in the post-mastectomy setting. Although not implying causation, further work is required to corroborate the conclusions herein.

Purpose: Most women with cervical cancer in Sub-Saharan Africa present with locally advanced disease. These women require external beam radiation therapy and brachytherapy for curative treatment, but data on their outcomes remain sparse. We report data on treatment characteristics, follow-up, toxicity, and cancer outcomes in a large population of patients from the National Centre for Radiotherapy in Accra, Ghana., Methods and Materials: The charts of patients treated from 2006 to 2011 were reviewed. Patients treated without brachytherapy or with palliative intent were excluded. Staging computed tomography scans were not routinely performed. Cobalt 60 external beam radiation therapy was followed by 2 low-dose-rate brachytherapy insertions. Concurrent weekly cisplatin was recommended. Because many patients experienced delays from diagnosis to treatment, we calculated overall survival and locoregional recurrence from the date of first radiation therapy to the event date-or last follow-up when no event recurred-using the Kaplan-Meier (product-limit) method., Results: We included 250 patients with a median age at diagnosis of 55 years. The International Federation of Gynecology and Obstetrics stage was IIB or lower in 63% of patients. The median dose to point A was 83 Gy (range, 60-97.5 Gy). The median doses to the bladder and rectal points were 71 Gy and 65 Gy, respectively. Of the patients, 69% received ≥4 cycles of concurrent cisplatin. The median overall treatment time was 73 days. The median follow-up period was 2.4 years, with 3-year overall survival and locoregional recurrence rates of 86% and 19%, respectively. The most commonly reported late side effect was vaginal stenosis and shortening, occurring in 32% of patients. We also identified nearly 300 patients who were offered curative treatment but never returned to start treatment., Conclusions: We report promising outcomes in a population of women with cervical cancer treated with concurrent chemoradiation therapy and brachytherapy in Ghana. To our knowledge, this is the largest series of its kind, and it demonstrates what can be achieved with a well-established cancer program in Sub-Saharan Africa., (Copyright © 2017 Elsevier Inc. All rights reserved.)

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.

Purpose: To analyze the toxicities and dose-volume histogram parameters of external-beam and magnetic resonance imaging-based intracavitary brachytherapy in cervical cancer patients., Methods and Materials: Acute and late toxicities were assessed in 135 patients divided into four groups: group 1, grade 0; group 2, grades 1-4; group 3, grades 0-1; and group 4, grades 2-4. The doses at the International Commission on Radiation Units and Measurements (D ICRU ) and minimum doses to the most exposed 0.1, 1, 2, and 5 cc (D 0.1cc , D 1cc , D 2cc , and D 5cc ) of normal organs were calculated as equivalent doses in 2 Gy (α/β = 3)., Results: The median follow-up was 35.2 months. For rectum, D ICRU , D 0.1cc , D 1cc , and D 2cc were significantly different between groups 1 and 2 and D ICRU , D 0.1cc , and D 1cc between groups 3 and 4. For bladder, D 0.1cc , D 1cc , and D 2cc were significantly different between groups 1 and 2 and D ICRU , D 1cc , D 2cc , and D 5cc between groups 3 and 4. Grade 2-4 bladder toxicity occurred in fewer patients with D 2cc  ≤ 95 Gy than those with D 2cc  > 95 Gy (7% vs. 22%, p = 0.014)., Conclusions: D ICRU , D 0.1cc , D 1cc , and D 2cc are relevant for predicting late rectal toxicities. The patients with bladder D 2cc  > 95 Gy are required to be in close observation for severe late toxicities., (Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Objective: To determine prognostic factors for progression-free survival (PFS) and overall survival (OS) for stage I-II cervical-cancer patients treated using computed-tomography (CT)-planned high-dose-rate (HDR) intracavitary brachytherapy (BT)., Methods: A total of 150 patients were treated for Stage I-II cervical cancer using CT-planned BT between 4/2004 and 10/2014. Of these, 128 were eligible for inclusion. Kaplan-Meier local control (LC), pelvic control (PC), overall survival (OS), and PFS estimates were calculated., Results: After a median follow-up of 30months, the 2-year LC rate was 96%, PFS was 88%, and OS was 88%. Overall, 18 patients (14%) experienced any recurrence (AR), 8 had distant recurrence only and 10 had a combination of local, pelvic, regional, and distant recurrence. No patients had LR only. A prognostic factor for AR was tumor size >4cm (p=0.01). Patients with tumors >4cm were 3.3 times more likely to have AR than those with tumors ≤4cm (hazard ratio [HR]=3.3; 95% confidence interval [CI] 1.28-9.47). Point A was 85% of prescription for tumors < 4 cm and decreased approximately 3% over 5 fractions compared to 90% of prescription for tumors > 4 cm that decreased approximately 4% over 5 fractions. Two patients (2%) experienced grade≥2 late toxicity. There were no acute or late grade≥3 toxicities., Conclusion: CT-planned BT resulted in excellent local control and survival. Large tumor size was associated with an increased risk of recurrence outside the radiation field and worse PFS and OS. A volume-optimized plan treated a smaller area than a point A standard plan for patients with Stage I-II cervical cancer that have received chemoradiation. Given the outstanding LC achieved with modern therapy including chemoradiation, HDR, and image-based BT, further efforts to combat spread outside the radiation field with novel therapies are warranted., (Copyright © 2016 Elsevier Inc. All rights reserved.)

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.

Background: This study investigated the clinical manifestations of lower extremity edema (LEE) in locally advanced cervical cancer patients treated with two different strategies., Methods: In total, 79 cervical cancer survivors with International Federation of Gynecology and Obstetrics stage IB2-IIB were included. Six survivors with stage IB1 and who had been suspicious for lymph node metastasis on pretreatment image also were included. Forty-two patients received radiotherapy after pretreatment laparoscopic surgical staging (Group 1), and 43 patients received primary radiotherapy (Group 2). The patients' medical records and survey results of the Korean version of the Gynecologic Cancer Lymphedema Questionnaire (GCLQ-K) were analyzed., Results: The incidence of LEE was higher in Group 1 than in Group 2 (69.0 vs. 11.6 %; P < 0.001). The duration of LEE was longer in Group 1 (mean 77.3 vs. 9.4 months). At the time of survey, 47.6 % of the patients in Group 1 were clinically diagnosed with lymphedema compared with no patients in Group 2. In GCLQ-K, the mean symptom cluster scores for general swelling (0.74 vs. 0.09; P < 0.001), limb swelling (0.22 vs. 0.00; P = 0.006), and heaviness (0.45 vs. 0.23; P = 0.033) were significantly higher in Group 1. One patient in Group 1 developed lymphedema-related angiosarcoma that was diagnosed at 7.8 years after surgery., Conclusions: Patients with cervical cancer who underwent radiotherapy after laparoscopic surgical staging more commonly experienced LEE and related symptoms than patients who underwent primary radiotherapy. As LEE decreases patients' quality of life, it should be considered during patient consultation and surveillance.

Background: The time course of human papillomavirus (HPV) DNA clearance was studied in patients with carcinoma of the cervix during follow-up after primary radical radiotherapy (RT). This study investigated the relationship between timing of HPV clearance and RT effectiveness., Patients and Methods: A total of 71 consecutive patients who were treated for cervical cancer with primary radical radiotherapy and high-dose rate intracavitary brachytherapy with or without chemotherapy were enrolled in the study. Samples for HPV DNA examination were taken before (1) treatment, (2) every brachytherapy, and (3) every follow-up examination. The times when HPV DNA was undetected were analyzed for association with recurrence-free survival., Results: HPV DNA was not detected in 13 patients (18 %) before RT. Of the 58 patients with HPV DNA detected before treatment, HPV DNA was not detected in 34 % during treatment and in 66 % after the treatment. Within 6 months after RT, HPV DNA was detected in 0 % of all patients. The patients were followed up for a median period of 43 months (range 7-70 months). In all, 20 patients were found to develop recurrence. The 3-year cumulative disease-free survival (DFS) rate was 71 ・} 5.4 % for all 71 patients. In multivariate analysis, DFS was significantly associated with HPV (detected vs. not detected) with a hazard ratio of 0.07 (95 % confidence interval 0.008-0.6, p = 0.009)., Conclusion: In this study, patients in whom HPV was not detected had the worst prognosis. Six months after RT, HPV DNA was detected in 0 % of the patients. Patients in whom HPV DNA could not be detected before treatment need careful follow-up for recurrence and may be considered for additional, or alternative treatment.

Objective: Since the Group Européen de Curiethérapie and the European Society for Radiotherapy and Oncology (GEC-ESTRO) published recommendations for 3D MRI-based image-guided adaptive brachytherapy (IGBT) in the treatment of cervical cancer, many institutions have implemented this technique and favourable results were documented. We investigated if introduction of IGBT in our centre indeed improved treatment outcomes and reduced toxicity compared to conventional brachytherapy (CBT)., Methods: A retrospective analysis was done of outcomes of patients with stage IB-IVA cervical cancer treated with primary radiation therapy with curative intent between 2000 and 2012. Outcome measures were overall and disease-free survival, pelvic control, distant metastasis and treatment related adverse events (AE)., Results: 126 patients were analysed; 43 had been treated with CBT between 2000-2007, and 83 with IGBT between 2007-2012. External beam radiation (mean; 46.6Gy) was combined with concurrent weekly cisplatin (51.6%), or hyperthermia (24.6%); radiation alone was used in 23.8%. Median follow-up was 121.8months for CBT patients, vs. 42.3months for IGBT. Complete remission was achieved in 83.7% of patients in the CBT group and in 98.8% of IGBT patients (p<0.01). Overall survival at 3years was 51% and 86%, respectively (p=0.001). Pelvic recurrence was found in 32% vs. 7% (p<0.001). Most patients had low grade adverse events. High grade (3-4) AE occurred in 15.4% vs. 8.4% at 3years (p=0.06)., Conclusion: Introduction of IGBT for cervical cancer has led to significantly increased 3-year locoregional control and survival rates, whilst reducing late morbidity., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: The objective of this study was to find out predictive factors of tumor control as well as acute and late radiation reactions in treatment of advanced cervical carcinomas., Methods: In a series of 134 primary cervical carcinomas in International Federation of Gynecology and Obstetrics stages I to IV treated with combined external pelvic and intraluminal cervical-vaginal brachytherapy, predictive and prognostic factors were analyzed with regard to tumor control, recurrences, survival data, and adverse effects. Concomitant chemotherapy was given to 48 patients (35.8%). The external beam therapy was given with a 4-field technique (50-60 Gy) and brachytherapy was given with a high-dose rate (iridium-192) afterloading technique using a ring applicator set. A computed tomographically based 3-dimensional dose-planning system was used for the external beam therapy and for the brachytherapy planning. The mean age of the patients was 65 years. A total of 110 tumors were squamous cell carcinomas and 24 were adenocarcinomas or adenosquamous carcinomas. A total of 111 tumors were in International Federation of Gynecology and Obstetrics stages I to II; 23 tumors, in stages III to IV., Results: The primary control rate of the complete series was 92.5%. Tumor size, the brachytherapy dose, the combined external and brachytherapy dose, as well as the number of days of interruption (delay) of irradiation were all significant predictive factors for local tumor control. Forty recurrences (30%) were recorded. Early radiation reactions were recorded in 67% (mostly grade 1) and were associated with the widths of the anterior-posterior and lateral pelvic fields. Serious late radiations reactions (grade 3-4) were noted in 11%., Conclusions: The width of the lateral pelvic fields, left point A and B doses, dose to the rectal reference point, as well as asymmetry of the dose distribution were associated with late severe reactions. Prior abdominal and pelvic surgery was also a high-risk factor for late tissue reactions. Concomitant chemotherapy did not increase the risk for acute or late toxicity.

Objective: To compare tumor characteristics and clinical outcome of patients with cervical locally advanced adenocarcinoma (AC)/adenosquamous carcinoma (ASC) and squamous cell carcinoma (SCC)., Design: Retrospective study., Setting: National Taiwan University Hospital, Taipei, Taiwan., Population: All patients with cervical SCC (n = 35), AC or ASC (n = 194) with FIGO stage ≥IIB who received definitive radiotherapy or concurrent chemoradiotherapy (CCRT) from January 1995 to December 2009., Method: Medical and histopathological record review., Main Outcome Measures: Progression-free survival (PFS), local recurrence-free survival, distant metastasis-free survival, and overall survival (OS)., Results: Compared with the SCC subgroup, patients with AC/ASC were significantly younger (p = 0.007), more of them without clinical symptoms were diagnosed by abnormal Pap smear findings (p = 0.043), and less responded to treatment (p = 0.018). After a median follow-up of 59.3 months, patients with AC/ASC had worse 5-year PFS (30.0% vs. 47.6%, p = 0.044), worse 5-year distant metastasis-free survival (41.5% vs. 69.9%, p = 0.005), and trends toward worse 5-year local recurrence-free survival (64.4% vs. 76.2%, p = 0.165) and worse 5-year OS (41.3% vs. 58.1%, p = 0.090) than patients with SCC. In univariate analysis, early FIGO stage and complete treatment response were significantly associated with PFS and OS. Histology of non-AC/ASC and Point A biologically equivalent doses in 2-Gy fractions >85 Gy were significantly associated with better PFS, and CCRT was significantly associated with better OS. In multivariate analysis, complete treatment response and early FIGO stage remained significant factors for predicting better PFS and OS., Conclusions: Cervical AC/ASC may be more aggressive than is SCC. For cervical AC/ASC, more comprehensively effective treatments are warranted., (© 2014 Nordic Federation of Societies of Obstetrics and Gynecology.)

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.

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.)

Objective: To evaluate the prognostic influence of adenocarcinoma (AC) and adenosquamous carcinoma (ASC) in patients with FIGO stage IB-IIA cervical cancer who received radical hysterectomy followed by adjuvant radiotherapy (RT) or concurrent chemoradiotherapy (CCRT)., Methods: We analyzed 1323 patients who satisfied the following criteria: histologically proven squamous cell carcinoma (SCC), AC, or ASC of the uterine cervix; FIGO stage IB-IIA disease; no history of neoadjuvant chemotherapy; and a history of radical hysterectomy with pelvic lymph node (PLN) dissection, followed by postoperative pelvic RT at a dose ≥ 45 Gy. The median age was 50 years. Median RT dose delivered to the whole pelvis was 50.4 Gy, and 219 (16.6%) patients received brachytherapy at a median dose of 24 Gy. Concurrent chemotherapy was delivered to 492 (37.2%) patients., Results: Pathologic risk factors were not different according to pathologic subtype. The median follow-up duration was 75.7 months. Locoregional recurrence-free survival, relapse-free survival (RFS), and overall survival were significantly affected by histology, tumor size, PLN metastasis, parametrial invasion, lymphovascular invasion, and deep stromal invasion. The 5-year RFS rates were 83.7%, 66.5%, and 79.6% in patients with SCC, AC, and ASC histology, respectively (P<0.0001). By multivariate analysis, AC histology was the only significant prognostic factor affecting all survival outcomes., Conclusions: AC histology was associated with poor survival outcomes in patients with FIGO stage IB-IIA cervical cancer who received adjuvant RT or CCRT. Prognosis of ASC histology was closer to that of SCC histology than that of AC histology., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose of Investigation: To add to the existing outcome data regarding radical radiotherapy (RT) for FIGO Stage I and II cervical cancer in a mono-institutional series and to evaluate the cost-benefit ratio of the addition of brachytherapy (BRA) to external-beam radiotherapy (EBRT)., Materials and Methods: The authors report on 240 patients (pts) with FIGO Stage I and II cervical cancer, consecutively treated with radical RT from 1990 through 2009 at the Istituto del Radio "O. Alberti" (EBRT alone, 32, EBRT and BRA, 189, BRA alone, 19). BRA was delivered with low dose rate (LDR, 133.64%) until 2003 and then with high dose rate (HDR, 75.36%). RT was associated with concomitant chemotherapy (CHT), mainly weekly cisplatin 40 mg/m2, in 87 pts, mostly after 2000. The Chi-square test was used to compare the different variables, the Log-Rank test to compare the actuarial survival values, and the Cox-model for the multivariate analysis., Results: Five-year actuarial overall survival (OS) equalled 65%, disease specific survival (DSS) 77%. Regardless of disease stage, better DSS was evident in pts treated with EBRT and BRA compared with those treated with EBRT alone (82% and 58% respectively, p = 0.005); pts treated with concomitant CHT (dose intensity > or = 50%) and higher RT doses (RT cumulative EQD2 > or = 75 Gy) obtained better DSS. Complete response (CR) rate approached 88.4% (206/233 evaluable pts) and more than half of the subsequent failures (21/36) were in distant sites. Older patients and those given BRA had better OS and DSS, while BRA dose rate did not result related with these outcomes. Chronic G3/G4 toxicity involved more frequently the intestinal/rectal tract than other organs at risk. Rectal and vaginal serious chronic sequelae developed mainly in pts treated with EBRT and BRA and suggest the need for more advanced treatment techniques., Conclusions: the present mono-institutional analysis confirms the efficacy of radical RT for the treatment of cervical cancer and provides support to the role of BRA to obtain better outcomes. An effort to reduce long-term toxicity of the treatment is needed.

We report the case of a 33-year-old lactating woman who presented with a 10-cm breast abscess. Biopsy of the abscess wall revealed a poorly differentiated invasive ductal carcinoma. The patient had no family history of breast cancer or other risk factors for breast cancer. The disease was considered to be a large noninflammatory invasive breast cancer, for which the patient received neoadjuvant chemotherapy, breast-conserving surgery using axillary dissection (the patient did not consent to a mastectomy), and postoperative radiotherapy. Final histologic examination revealed a 4-cm, triple negative, high-grade adenosquamous carcinoma. At follow-up four years after surgery, the patient was doing well with no signs of recurrence. Adenosquamous carcinoma is an extremely rare disease that mainly presents in low-grade forms. High-grade forms are aggressive and frequently present with axillary involvement. To the best of our knowledge, there has been no report of adenosquamous carcinoma presenting as a breast abscess in the literature. The case we report highlights that, although rare, cancer should be considered in lactating breast abscesses.

Objective: Pure epithelial breast metaplastic carcinoma is a rare and highly malignant tumor. In this study, our purpose was to analyze the clinical features, treatment method and prognostic factors, so to explore the approach for early diagnosis and appropriate treatment of this cancer., Methods: Clinical data of 22 patients with histopathologically confirmed pure epithelial breast metaplastic carcinoma and treated at Tianjin Cancer Hospital from 1974 to 2008, were reviewed retrospectively. Survival rate was calculated by life tables. Kaplan-Meier unvariate analysis and Log-rank test were used to compare the survival rates. Multivariate factors for survival were analyzed by Cox proportional hazards regression model., Results: The median age of the 22 cases of pure epithelial breast metaplastic carcinoma was 52.5 years. Among them 20 cases went to see a doctor for painless mass, and two cases shown as skin inflammation. Clarifying a diagnosis was difficult before operation so that its diagnosis mainly depended on postoperative histopathologic examination. Twelve cases had axillary lymph node metastasis, 7 cases distant metastasis, and the lung was the most common metastatic organ. The 5-year survival rate was 55.6%, with a median follow-up of 46 months. It was found by Kaplan-Meier unvariate analysis that the age (P = 0.044), number of positive axillary lymph nodes (P = 0.011) and therapeutic schedule (P = 0,003) significantly influenced the outcome of the patients, but tumor size (P = 0.194) was not. Cox multivariate analysis results showed that number of positive axillary lymph nodes was independent prognostic factor for pure epithelial breast metaplastic carcinoma (P = 0.038)., Conclusions: Pure epithelial breast metaplastic carcinoma is seldom seen. It is easy to cause distant metastasis and has a poor prognosis. ER, PR and HER-2 expressions in most samples are negative. The more axillary lymph nodes have metastasis, the poorer is the prognosis. A reasonable and comprehensive treatment can improve the prognosis obviously.

Objective: The objective of this study was to compare morbidity and outcome following radical surgery with or without adjuvant radiation therapy (RT) in the treatment of stages IB1-IB2 cervical carcinoma., Methods: We retrospectively identified 222 patients with stages IB1-IB2 cervical carcinoma treated initially with radical hysterectomy or radical trachelectomy with or without adjuvant RT from February 2000 to November 2009. All grade 3 or higher complications-those requiring interventional radiology, endoscopic evaluation, or operative intervention-were documented., Results: One hundred fifty-eight patients (71%) underwent radical hysterectomy; 64 (29%) underwent radical trachelectomy. One hundred fifty-three patients (69%) underwent surgery alone; 69 (31%) received adjuvant radiation with or without chemosensitization. There was a statistically significant difference in the rate of total grades 1 to 5 late complications between the surgery-alone and surgery + RT groups (12% vs 32%, respectively; P < 0.001); however, the rate of grade 3 or higher complications was similar (5% vs 4%, respectively; P = 0.999). The progression-free and overall survival rates of the entire cohort were both 95%. The 5-year progression-free survival rates for the surgery-alone and surgery + RT groups were 93% and 90% (P = 0.172). The overall survival rates were 96% and 91%, respectively (P = 0.332)., Conclusions: The majority of women with stages IB1-IB2 cervical cancer undergoing radical surgery do not require adjuvant RT, have excellent oncologic outcome, and have low severe complication rates. Nearly one third of our patients required postoperative radiation, with no statistically significant increase in severe complication rate and with similar oncologic outcomes compared with the surgery-only cohort. These data support the continued practice of radical surgery with individualized postoperative radiation for these patients.

Purpose: To study the efficacy of low-dose-rate californium-252 ((252)Cf) neutron intracavitary afterloading radiotherapy (RT) combined with external pelvic RT for treatment of cervical cancer., Methods and Materials: The records of 96 patients treated for cervical cancer from 2006 to 2010 were retrospectively reviewed. For patients with tumors ≤4 cm in diameter, external beam radiation was performed (1.8 Gy/day, five times/week) until the dose reached 20 Gy, and then (252)Cf neutron intracavitary afterloading RT (once/week) was begun, and the frequency of external beam radiation was changed to four times/week. For patients with tumors >4 cm, (252)Cf RT was performed one to two times before whole-pelvis external beam radiation. The tumor-eliminating dose was determined by using the depth limit of 5 mm below the mucosa as the reference point. In all patients, the total dose of the external beam radiation ranged from 46.8 to 50 Gy. For (252)Cf RT, the dose delivered to point A was 6 Gy/fraction, once per week, for a total of seven times, and the total dose was 42 Gy., Results: The mean ± SD patient age was 54.7 ± 13.7 years. Six patients had disease assessed at stage IB, 13 patients had stage IIA, 49 patients had stage IIB, 3 patients had stage IIIA, 24 patients had stage IIIB, and 1 patient had stage IVA. All patients obtained complete tumor regression (CR). The mean ± SD time to CR was 23.5 ± 3.4 days. Vaginal bleeding was fully controlled in 80 patients within 1 to 8 days. The mean ± SD follow-up period was 27.6 ± 12.7 months (range, 6-48 months). Five patients died due to recurrence or metastasis. The 3-year survival and disease-free recurrence rates were 89.6% and 87.5 %, respectively. Nine patients experienced mild radiation proctitis, and 4 patients developed radiocystitis., Conclusions: Low-dose-rate (252)Cf neutron RT combined with external pelvic RT is effective for treating cervical cancer, with a low incidence of complications., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: To determine the patterns of failure in patients with cervical cancer treated with definitive radiotherapy and evaluated for metabolic response with early posttherapy (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET)., Methods and Materials: The records of 238 patients with cervical cancer were reviewed. All patients were treated with a combination of external radiotherapy and intracavitary brachytherapy. Two hundred and nineteen patients (92%) received concurrent chemotherapy. All patients underwent pretreatment FDG-PET, and posttherapy FDG-PET was performed within 8-16 weeks of the completion of radiotherapy. Posttherapy FDG-PET results were categorized as complete metabolic response (CMR), partial metabolic response (PMR), and progressive disease (PD). Failure patterns were categorized as none, isolated local failure (central pelvis ± pelvic lymph nodes), distant failure, or combined local plus distant failure., Results: Of the 91 patients (38%) who had a recurrence, 22 had isolated local failures, and 69 had distant failures (49 distant failures and 20 combined local plus distant failures). Of the 173 patients with a CMR, 40 (23%) experienced treatment failure. All 25 patients with PD experienced treatment failure, which was distant in 24 patients (96%). Among the 40 patients with PMR, no failure has been observed for 14 patients (35%). Of the 26 failures within the PMR group, 15 (58%) were limited to the pelvis. Differences in the patterns of failure between the three groups (CMR, PMR, PD) were statistically significant (chi-square test; p < 0.0001)., Conclusions: The majority of failures after definitive radiotherapy for cervical cancer include distant failures, even in the setting of concurrent chemotherapy. PMR within the cervix or lymph nodes is more commonly associated with isolated local recurrence., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: To determine the effectiveness and rate of complications of intensity-modulated radiotherapy (IMRT) in the treatment of cervical lymph node metastases from unknown primary cancer., Methods and Materials: Between February 2005 and November 2008, 25 patients with an unknown primary cancer underwent IMRT, with a median radiation dose of 70 Gy. The bilateral neck and ipsilateral putative pharyngeal mucosa were included in the target volume. All patients had squamous cell carcinoma, except for 1 patient who had adenosquamous differentiation. They were all treated with curative intent. Of the 25 included patients, 20 were men and 5 were women, with a median age of 54 years. Of these patients, 3 had Stage III, 18 had Stage IVa, and 4 had Stage IVb. Of the 25 patients, 18 (72%) received platinum-based chemotherapy in a combined-modality setting. Neck dissection was reserved for residual disease after definitive IMRT. Overall survival, disease-free survival, and locoregional control were calculated using the Kaplan-Meier method., Results: With a median follow-up of 38 months, the overall survival, disease-free survival, and locoregional control rates were all 100% at 3 years. No occurrence of primary cancer was observed during the follow-up period. The reported rates of xerostomia reduced with the interval from the completion of treatment. Nine patients (36%) reported Grade 2 or greater xerostomia at 6 months, and only 2 (8%) of them reported the same grade of salivary function toxicity after 24 months of follow-up., Conclusion: In our institution, IMRT for unknown primary cancer has provided good overall and disease-free survival in all the patients with an acceptable rate of complications. IMRT allowed us to address the bilateral neck and ipsilateral putative pharyngeal mucosa with minimal late salivary function toxicity. The use of concurrent chemotherapy and IMRT for more advanced disease led to good clinical results with reasonable toxicities., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: Locally advanced bulky cervical cancer (LABCC) is characterized by poor local control. The objective of this study was to identify the clinicopathologic variables associated with one-year central-only recurrence, which will serve as criteria for adjuvant hysterectomy after radiation (AHR) in patients with LABCC., Study Design: Between January 2000 and August 2007, we retrospectively evaluated outcomes in 225 patients with LABCC who were initially treated with radiation or chemoradiation., Results: Among the 225 patients with LABCC, there were 41 recurrences within one year after treatment (8 central-only and 33 pelvis and/or distant site recurrences). Age, stage, and treatment type were not associated with the one-year central-only recurrences, but tumor size ≥8cm had a statistically significant association based on multivariate analysis (OR, 5.39; 95% CI, 1.15-25.31; p=0.03). The combination of non-squamous cell (non-SCC) type and tumor size ≥8cm had a significantly higher rate of recurrence within one year (OR, 43.0; 95% CI, 4.78-386.68; p<0.01)., Conclusions: Of patients with LABCC, those with non-SCC tumors ≥8cm in size were at high risk for early central-only recurrence after cisplatin-based chemoradiation, and represent the subset of patients for whom AHR is beneficial., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Purpose: One major uncertainty in radiotherapy planning of non-small-cell lung cancer concerns the definition of the clinical target volume (CTV), meant to cover potential microscopic disease extension (MDE) around the macroscopically visible tumor. The primary aim of this study was to establish pretreatment risk factors for the presence of MDE. The secondary aim was to establish the impact of these factors on the accuracy of positron emission tomography (PET) and computed tomography (CT) to assess the total tumor-bearing region at pathologic examination (CTV(path))., Methods and Materials: 34 patients with non-small-cell lung cancer who underwent CT and PET before lobectomy were included. Specimens were examined microscopically for MDE. The gross tumor volume (GTV) on CT and PET (GTV(CT) and GTV(PET), respectively) was compared with the GTV and the CTV at pathologic examination, tissue deformations being taken into account. Using multivariate logistic regression, image-based risk factors for the presence of MDE were identified, and a prediction model was developed based on these factors., Results: MDE was found in 17 of 34 patients (50%). The MDE did not exceed 26 mm in 90% of patients. In multivariate analysis, two parameters (mean CT tumor density and GTV(CT)) were significantly associated with MDE. The area under the curve of the two-parameter prediction model was 0.86. Thirteen tumors (38%, 95% CI: 24-55%) were identified as low risk for MDE, being potential candidates for reduced-intensity therapy around the GTV. In the low-risk group, the effective diameter of the GTV(CT/PET) accurately represented the CTV(path). In the high-risk group, GTV(CT/PET) underestimated the CTV(path) with, on average, 19.2 and 26.7 mm, respectively., Conclusions: CT features have potential to predict the presence of MDE. Tumors identified as low risk of MDE show lower rates of disease around the GTV than do high-risk tumors. Both CT and PET accurately visualize the CTV(path) in low-risk tumors but underestimate it in high-risk tumors., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: To evaluate treatment outcomes of locally advanced cervical cancer patients who received concurrent weekly carboplatin with radiation therapy., Methods: Patients with locally advanced cervical cancer who had primary radiation treatment in concurrent with weekly carboplatin (100mg/m(2) or AUC 2) from 1997 to 2008 were identified. Demographic data, chemotherapy cycles, total treatment time, toxicities, and treatment outcomes were recorded., Results: One hundred and forty-eight patients with stage IIB (50.7%), IIIB (48.0%) and IVA (1.3%) cervical cancer patients were included in the study. Median total treatment time was 53.5 days (range, 45-100 days). Carboplatin was given for a median number of 6 cycles (range, 3-6 cycles). Complete response was achieved in 142 patients (95.9%) while six (4.1%) had persistent diseases. Among the 142 responders, 36 experienced recurrences: pelvic recurrences in seven (4.7%), distant failure in 25 (16.9%), and both pelvic and distant in four (2.7%). The 2-year and 5-year progression-free survival rates were 75.1% and 63.0%, respectively with the corresponding 2-year and 5-year overall survival rates of 81.9% and 63.5%. No grade 3 or 4 hematologic and non-hematologic toxicities were observed during treatment in any patients. Late grade 3-4 gastrointestinal or genitourinary toxicities were 10.1% and 0.7%, respectively., Conclusion: Concurrent weekly carboplatin with radiation therapy yields high response rate with modest progression-free and overall survivals in locally advanced cervical cancer. The regimen is feasible with minimal toxicities., (Copyright © 2011 Elsevier Inc. All rights reserved.)

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.

Purpose: To study the outcomes of patients with adenocarcinoma/adenosquamous carcinoma (AC/ASC) of the cervix primarily treated with radiotherapy (RT), identify the prognostic factors, and evaluate the efficacy of concurrent chemoradiotherapy (CCRT) or salvage surgery., Methods and Materials: A total of 148 patients with Stage I-IVA AC/ASC of cervix after full-course definitive RT were included. Of the 148 patients, 77% had advanced stage disease. Treatment failure was categorized as either distant or local failure. Local failure was further separated into persistent tumor or local relapse after complete remission. The effectiveness of CCRT with cisplatin and/or paclitaxel was examined, and the surgical salvage rate for local failure was reviewed., Results: The 5-year relapse-free survival rate was 68%, 38%, 49%, 30%, and 0% for those with Stage IB/IIA nonbulky, IB/IIA bulky, IIB, III, and IVA disease, respectively, and appeared inferior to that of those with squamous cell carcinoma of the cervix treated using the same RT protocol. Incomplete tumor regression after RT, a low hemoglobin level, and positive lymph node metastasis were independent poor prognostic factors for relapse-free survival. CCRT with weekly cisplatinum did not improve the outcome for our AC/ASC patients. Salvage surgery rescued 30% of patients with persistent disease., Conclusion: Patients with AC/ASC of the cervix primarily treated with RT had inferior outcomes compared to those with squamous cell carcinoma. Incomplete tumor regression after RT was the most important prognostic factor for local failure. Salvage surgery for patients with persistent tumor should be encouraged for selected patients. Our results did not demonstrate a benefit of CCRT with cisplatin for this disease., (Copyright © 2011. Published by Elsevier Inc.)

Background: Unresectable hepatic metastases from aerodigestive cancers are common and in most cases herald a poor prognosis. A small percentage of patients maybe amenable to surgical resection or ablation once the biology of the disease and the burden of hepatic disease are better understood. The use of hepatic arterial resin microspheres containing the β emitter, yttrium-90, has been reported in the treatment of unresectable hepatic metastases. The goal of this review was to evaluate the use of yttrium-90 hepatic arterial therapy in the management of hepatic metastases and surgical downstaging., Methods: We reviewed our prospective hepatic arterial therapy registry and found 44 patients who had received Sir Sphere treatment for unresectable hepatic malignancies from 11/06 to 7/08. Response was assessed by using CT-imaging and characterized using modified response evaluation criteria in solid tumors (RECIST). All patients were managed in a multidisciplinary tertiary referral center specializing in hepatic malignancies., Results: A total of 44 patients, 34 men and 10 women, with a median age of 60 y (range 44-8), received 67 treatments. The disease types treated were one adenosquamous tongue, one adrenal, nine carcinoid, three cholangiocarcinoma, four esophageal, one gastric, one gastrinoma, one GIST, four HCC, 15 colorectal, one melanoma, one non-small-cell lung, one occular, and one sarcoma. Four patients treated proceeded to resection because of downstaging of disease or no evidence of extrahepatic progression. The median age in these patients was 61 y (range 49-62). All of the patients had less than 25% tumor burden in the liver. Surgical therapy consisted of two patients undergoing right hepatic lobectomy, one patient who also underwent two wedge resections of segment 3, and one patient who had a left lateral hepatectomy with right lobe microwave ablation. The median length of postoperative stay was 7 d. There was no evidence of liver dysfunction following resection in any of the patients. None of the patients show evidence of recurrence in the liver following resection. One patient has had progression of disease in the lungs following resection, histologically confirmed as metastatic rectal carcinoma. All of the patients are currently alive with a median survival of 2 y., Conclusion: Hepatic directed yttrium-90 is a minimally invasive, highly effective therapy that can be utilized to downstage the hepatic burden and/or assess the biology of the disease to allow for appropriate treatment. The use of yttrium-90 microspheres for radio-embolization of metastases in the liver can successfully downstage the lesions to allow for surgical resection in patients with amenable predictors, and can provide a significantly better prognosis in these patients. This form of therapy for the purposes of downstaging tumors for resection merits more extensive study in order to provide the best possible outcomes for patients with metastatic liver disease., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: The role of radiation therapy (RT) is unclear for metaplastic breast cancer (MBC). We hypothesized that RT would improve overall survival (OS) and disease-specific survival (DSS)., Materials and Methods: We used the Surveillance, Epidemiology, and End Results (SEER) database to identify MBC patients diagnosed from 1988 to 2006. Univariate analyses of patient, tumor, and treatment-specific factors on OS and DSS were performed using the Kaplan-Meier method and differences among survival curves assessed via log rank. Variables assessed included patient age, race/ethnicity, histologic subtype, tumor grade, T stage, N stage, M stage, hormone receptor status, surgery type, and use of RT. Cox proportional hazards models used all univariate covariates. Risks of mortality were reported as hazard ratios (HR) with 95% confidence intervals (95% CI); significance was set at P ≤ 0.05., Results: Among 1501 patients, RT was given to 580 (38.6%). Ten-year OS and DSS were 53.2, and 68.3%, respectively. In the overall analysis, RT provided an OS (HR 0.64; 95% CI, 0.51-0.82; P < 0.001) and DSS (HR 0.74; CI, 0.56-0.96; P < 0.03) benefit. When patients were stratified according to type of surgery, RT provided an OS but not a DSS benefit to lumpectomy (HR 0.51; CI, 0.32-0.79, P < 0.01) and mastectomy patients (HR 0.67; CI, 0.49-0.90; P < 0.01)., Conclusions: Our findings support the use of RT for patients with MBC following lumpectomy or mastectomy. These retrospective findings should be confirmed in a prospective clinical trial.

Cerebralmetastases from primary cervical carcinomas are very rare with a repeated incidence of 0. 5-1. 2% in various studies. A 46-year-old woman was initially diagnosed and treated for FIGO clinical stage II a cervical carcinoma. She was two gravid, two para. When 40 years old, she had a right hemicolectomy and chemotherapy, due to colon cancer. Her mother also had colon cancer, cervical cancer, and stomach cancer. She had habitually smoked ten/day for 26 years. First, she went to the outpatient clinic, due to abnormal vaginal bleeding. She had a biopsy of her cervix and was diagnosed with cervical cancer. She underwent a radical hysterectomy, bilateral salpingo-oophorectomy and pelvic lymphadenectomy. Pathological diagnosis was adenosquamous cell carcinoma of uterine cervix with extensive LVSI and pelvic lymph node metastasis (right internalil iac LN), myometrial invasion (depth 10 mm), anterior vaginal wall metastasis, but no metastasis of vaginal stump. She came to our hospital for radiotherapy. The woman received concurrent chemoradiotherapy(CCRT)with weekly CDDP 30 mg/m² as adjuvant therapy. Shortly after CCRT, she was diagnosed with multiple metastases to the bone, liver, lung, and brain. She received palliative radiotherapy and eventually died four months after being diagnosed. The extremely rapid progression of this patient's disease is unusual. To our knowledge, this is one of the most aggressive cases of cervical adenosquamous cell carcinoma documented.

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.

Purpose: To study the prognostic value of the human papillomavirus (HPV) genotypes in cervical cancer patients undergoing radiotherapy., Patients and Methods: A total of 1,010 patients with cervical cancer after radiotherapy between 1993 and 2000 were eligible for this study. The HPV genotypes were determined by a genechip, which detects 38 types of HPV. The patient characteristics and treatment outcomes were analyzed using the Cox regression hazard model and classification and regression tree decision tree method., Results: A total of 25 genotypes of HPV were detected in 992 specimens (98.2%). The leading 8 types were HPV16, 58, 18, 33, 52, 39, 31, and 45. These types belong to two high-risk HPV species: alpha-7 (HPV18, 39, 45) and alpha-9 (HPV16, 31, 33, 52, 58). Three HPV-based risk groups, which were independent of established prognostic factors, such as International Federation of Gynecology and Obstetrics stage, age, pathologic features, squamous cell carcinoma antigen, and lymph node metastasis, were associated with the survival outcomes. The high-risk group consisted of the patients without HPV infection or the ones infected with the alpha-7 species only. Patients co-infected with the alpha-7 and alpha-9 species belonged to the medium-risk group, and the others were included in the low-risk group., Conclusion: The results of the present study have confirmed the prognostic value of HPV genotypes in cervical cancer treated with radiotherapy. The different effect of the alpha-7 and alpha-9 species on the radiation response deserves additional exploration., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Background and Purpose: T2 weighted MRI is recommended for image guided adaptive brachytherapy (IGABT) in cervical cancer. Diffusion weighted imaging (DWI) and the derived apparent diffusion coefficient (ADC) may add additional biological information on tumour cell density. The purpose of this study was to evaluate the distribution of the ADC within target volumes as recommended by GEC-ESTRO: Gross Tumour Volume at BT (GTV(BT)), High-Risk Clinical Tumour Volume (HR-CTV) and Intermediate-Risk Clinical Target Volume (IR-CTV) and to evaluate the change of diffusion between fractions of IGABT., Material and Methods: Fifteen patients with locally advanced cervical cancer were examined by MRI before their first (BT1) and second (BT2) fraction of IGABT, resulting in a total of 30 MR examinations including both T2 weighted and DWI sequences. The Apparent Diffusion Coefficient (ADC) was calculated by use of three levels of b-values (0, 600, 1000 s/mm(2)). ADC maps were constructed and fused with the GEC ESTRO target contours. The mean ADC value within each target volume was calculated. Furthermore, volumes of low diffusion (ADC(low)) were defined based on an ADC threshold of 1.2 × 10(-3) mm(2)/s, and overlap with target volumes was evaluated. Change of ADC level in target volumes and change of ADC(low) volume from BT1 to BT2 was also evaluated., Results: The mean ADC was significantly lower in GTV(BT) than in HR-CTV (p<0.001) which again was significantly lower than in IR-CTV (p<0.001). There was no significant change of the ADC(low) volume or ADC level within each target structure between BT1 and BT2 (p=0.242). All three GEC-ESTRO volumes contained volumes with low diffusion. The GTV(BT) contained 37.2% volume of low diffusion, HR-CTV 20.3% and IR-CTV 10.8%., Conclusion: With DWI we were able to find a significant difference in ADC-values for the three different GEC ESTRO targets. This supports the assumption that the target volumes used for dose prescription in IGABT contain tissues with different characteristics, with the tumour (GTV(BT)) being the volume with the lowest diffusion. No significant changes were found from BT1 to BT2 indicating that changes of ADC level and volumes are stable at the time of BT. Further studies are needed to evaluate the role of DWI in target contouring and dose prescription for IGABT.

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.

Purpose: To investigate the feasibility of our novel image-based high-dose-rate interstitial brachytherapy (HDR-ISBT) for uterine cervical cancer, we evaluated the dose-volume histogram (DVH) according to the recommendations of the Gynecological GEC-ESTRO Working Group for image-based intracavitary brachytherapy (ICBT)., Methods and Materials: Between June 2005 and June 2007, 18 previously untreated cervical cancer patients were enrolled. We implanted magnetic resonance imaging (MRI)-available plastic applicators by our unique ambulatory technique. Total treatment doses were 30-36 Gy (6 Gy per fraction) combined with external beam radiotherapy (EBRT). Treatment plans were created based on planning computed tomography with MRI as a reference. DVHs of the high-risk clinical target volume (HR CTV), intermediate-risk CTV (IR CTV), and the bladder and rectum were calculated. Dose values were biologically normalized to equivalent doses in 2-Gy fractions (EQD(2))., Results: The median D90 (HR CTV) and D90 (IR CTV) per fraction were 6.8 Gy (range, 5.5-7.5) and 5.4 Gy (range, 4.2-6.3), respectively. The median V100 (HR CTV) and V100 (IR CTV) were 98.4% (range, 83-100) and 81.8% (range, 64-93.8), respectively. When the dose of EBRT was added, the median D90 and D100 of HR CTV were 80.6 Gy (range, 65.5-96.6) and 62.4 Gy (range, 49-83.2). The D(2cc) of the bladder was 62 Gy (range, 51.4-89) and of the rectum was 65.9 Gy (range, 48.9-76)., Conclusions: Although the targets were advanced and difficult to treat effectively by ICBT, MRI-aided image-based ISBT showed favorable results for CTV and organs at risk compared with previously reported image-based ICBT results., ((c) 2010 Elsevier Inc. All rights reserved.)

Purpose: This prospective randomized study was undertaken to determine the possible impact of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) on extrapelvic metastasis detection, radiation field design, and survival outcome for cervical cancer patients with enlarged pelvic nodes on MRI image., Methods and Materials: Inclusion criteria were patients with newly diagnosed Stage I-IVA cervical cancer and with positive pelvic but negative para-aortic lymph nodes (PALN) as detected by magnetic resonance image and good performance status for concurrent chemoradiotherapy. Eligible patients were randomized to receive either pretreatment FDG-PET (study group) or not (control group). Whole pelvis was the standard irradiation field for the control group and those with no extrapelvic findings on PET. The radiation fields for the rest of the study group were extended to include the PALN region or were modified according to the extrapelvic PET finding., Results: From January 2002 to April 2006, 129 patients were included, and 66 of them were randomized to receive FDG-PET. PET detected seven extrapelvic metastases (11%, 6 PALN and 1 omental node), and four of them remained disease-free after treatment modification. For patients who underwent PET compared with those who did not, there were no differences in the 4-year rates of overall survival (79% vs. 85%, p = 0.65), disease-free survival (75 % vs. 77%, p = 0.64), and distant metastasis-free survival (82% vs. 78%, p = 0.83)., Conclusions: Pretreatment FDG-PET in conjunction with magnetic resonance imaging can improve the detection of extrapelvic metastasis, mainly PALN, and help select patients for extended-field radiotherapy. However, the addition of FDG-PET may not translate into survival benefit, even though PALN relapses are reduced., (Copyright 2010 Elsevier Inc. All rights reserved.)

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.

Background: Adenosquamous carcinoma is an uncommon cutaneous malignant neoplasm with mixed glandular and squamous differentiation and a propensity for aggressive clinical behavior., Observations: Of 27 patients diagnosed as having adenosquamous carcinoma, 19 were men and 5 were immunosuppressed. The mean age was 74 years. The majority of tumors were located on the face and scalp (19 of 27 [70%]) or upper extremity (4 of 27 [15%]). Squamous and glandular differentiation was characteristic. Thickness of the primary lesion ranged from 1.2 to 9.2 mm, with all tumors extensively invading the reticular dermis. Perineural invasion was seen in 4 of 27 primary cases (15%). Although 3 of 6 patients treated with Mohs micrographic surgery had subsequent locoregional recurrences, there was no evidence of distant metastasis after a mean of 2.3 years of patient follow-up., Conclusions: Adenosquamous carcinoma is best considered as a locally aggressive high-risk subtype of cutaneous squamous cell carcinoma. Tumor thickness and perineural invasion are high-risk histopathological attributes, and immunosuppression is an important clinical risk factor. Although Mohs micrographic surgery may be the best initial treatment, locoregional recurrence is common.

Purpose: To describe patient characteristics and the process of radiotherapy (RT) for patients with esophageal cancer treated between 1999 and 2001 in Japan., Methods and Materials: The Japanese Patterns of Care Study (PCS) Working Group conducted a third nationwide survey of 76 institutions. Detailed information was accumulated on 621 patients with thoracic esophageal cancer who received RT., Results: The median age of patients was 68 years. Eighty-eight percent were male, and 12% were female. Ninety-nine percent had squamous cell carcinoma histology. Fifty-five percent had the main lesion in the middle thoracic esophagus. Fourteen percent had clinical Stage 0-I disease, 32% had Stage IIA-IIB, 43% had Stage III, and 10% had Stage IV disease. Chemotherapy was given to 63% of patients; 39% received definitive chemoradiotherapy (CRT) without surgery and 24% pre- or postoperative CRT. Sixty-two percent of the patients aged > or =75 years were treated with RT only. Median total dose of external RT was 60 Gy for definitive CRT patients, 60 Gy for RT alone, and 40 Gy for preoperative CRT., Conclusions: This PCS describes general aspects of RT for esophageal cancer in Japan. Squamous cell carcinoma accounted for the majority of patients. The standard total external RT dose for esophageal cancer was higher in Japan than in the United States. Chemoradiotherapy had become common for esophageal cancer treatment, but patients aged > or =75 years were more likely to be treated by RT only.

Purpose: To analyze the effect of adjuvant chemoradiotherapy on gallbladder carcinoma., Methods and Materials: We retrospectively reviewed the records from consecutive patients who underwent R0 resection of gallbladder carcinoma between January 1, 1985, and December 31, 2004. Patients had either Stage I (T1-T2N0M0) or Stage II (T3N0M0 or T1-T3N1M0) disease. Patients undergoing adjuvant therapy received 5-fluorouracil chemotherapy concurrently with radiotherapy (median dosage, 50.4 Gy in 28 fractions). Adverse prognostic factors and the effect of adjuvant treatment on overall survival (OS) were evaluated., Results: A total of 73 patients were included in the analysis; of these, 25 received adjuvant chemoradiotherapy. On univariate analysis, no adverse prognostic factors for OS reached statistical significance, but trends were noted for Stage N1 vs. N0 (p = .06), Nx vs. N0 (p = .09), Stage T3 vs. T1-T2 (p = .06), and histologic findings other than adenocarcinoma (p = .13). The median OS for patients receiving adjuvant chemoradiotherapy vs. surgery alone was 4.8 years and 4.2 years, respectively (log-rank test, p = .56). However, a significantly greater percentage of patients receiving adjuvant chemoradiotherapy had Stage II disease (p <.001). In the multivariate Cox model, increasing T and N category and histologic findings other than adenocarcinoma were significant predictors of decreased OS. Additionally, adjuvant chemoradiotherapy was a significant predictor of improved OS after adjusting for these prognostic factors (hazard ratio for death, 0.3; 95% confidence interval, 0.13-0.69; p = .004)., Conclusion: After adjusting for the stage parameters and histologic findings, our data suggest that adjuvant chemoradiotherapy might improve OS for patients with gallbladder cancer.