Mapping patterns of para-aortic lymph node recurrence in cervical cancer: a retrospective cohort analysis.

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. CTVRTOG was contoured based on the Radiation Therapy Oncology Group guideline. CTVK was contoured as proposed by Keenan et al. CTVM was contoured by expanding symmetrical margins around the aorta and inferior vena cava of 7 mm up to the T12-L1 interspace. CTVnew was created by modifying CTVRTOG 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. CTVRTOG, CTVK, and CTVM 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 CTVnew to cover 96.7% of all PALNs and all nodes in 91.4% of patients. CONCLUSION: CTVRTOG and CTVK 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.

Clinical Efficacy and Safety of Apatinib for the Treatment of Patients with Metastatic, Recurrent Cervical Cancer after Failure of Radiotherapy and First-Line Chemotherapy: A Prospective Study.

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.

Mutation profiling of uterine cervical cancer patients treated with definitive radiotherapy.

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.

Significance of PD-L1 expression in carbon-ion radiotherapy for uterine cervical adeno/adenosquamous carcinoma.

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.

A multi-institutional observational study on the effects of three-dimensional radiotherapy and weekly 40-mg/m2 cisplatin on postoperative uterine cervical cancer patients with high-risk prognostic factors.

BACKGROUND: The aim of this study was to evaluate the effects of treatment with both three-dimensional radiotherapy (3DRT) and weekly 40-mg/m2 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/m2 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/m2 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.

External Beam Radiation Therapy and Brachytherapy for Cervical Cancer: The Experience of the National Centre for Radiotherapy in Accra, Ghana.

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.

Metaplastic Breast Cancer: Practice Patterns, Outcomes, and the Role of Radiotherapy.

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.

Leptomeningeal metastasis of poorly differentiated uterine cervical adenosquamous carcinoma following reirradiation to metastatic vertebrae: A case report.

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.

Toxicities and dose-volume histogram parameters of MRI-based brachytherapy for cervical cancer.

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 (DICRU) and minimum doses to the most exposed 0.1, 1, 2, and 5 cc (D0.1cc, D1cc, D2cc, and D5cc) of normal organs were calculated as equivalent doses in 2 Gy (α/ß = 3). RESULTS: The median follow-up was 35.2 months. For rectum, DICRU, D0.1cc, D1cc, and D2cc were significantly different between groups 1 and 2 and DICRU, D0.1cc, and D1cc between groups 3 and 4. For bladder, D0.1cc, D1cc, and D2cc were significantly different between groups 1 and 2 and DICRU, D1cc, D2cc, and D5cc between groups 3 and 4. Grade 2-4 bladder toxicity occurred in fewer patients with D2cc ≤ 95 Gy than those with D2cc > 95 Gy (7% vs. 22%, p = 0.014). CONCLUSIONS: DICRU, D0.1cc, D1cc, and D2cc are relevant for predicting late rectal toxicities. The patients with bladder D2cc > 95 Gy are required to be in close observation for severe late toxicities.

Comparison of clinical outcomes of squamous cell carcinoma, adenocarcinoma, and adenosquamous carcinoma of the uterine cervix after definitive radiotherapy: a population-based analysis.

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.

Impact of histological subtype on survival in patients with locally advanced cervical cancer that were treated with definitive radiotherapy: adenocarcinoma/adenosquamous carcinoma versus squamous cell carcinoma.

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.

Outcomes with volume-based dose specification in CT-planned high-dose-rate brachytherapy for stage I-II cervical carcinoma: A 10-year institutional experience.

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.

Analysis of the effect of adjuvant radiotherapy on outcomes and complications after radical hysterectomy in FIGO stage IB1 cervical cancer patients with intermediate risk factors (GOTIC Study).

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.

Undetected human papillomavirus DNA and uterine cervical carcinoma: Association with cancer recurrence.

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.

Comparison of Lower Extremity Edema in Locally Advanced Cervical Cancer: Pretreatment Laparoscopic Surgical Staging with Tailored Radiotherapy Versus Primary Radiotherapy.

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.

Combined external and intracavitary irradiation in treatment of advanced cervical carcinomas: predictive factors for treatment outcome and early and late radiation reactions.

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.

Improved survival of patients with cervical cancer treated with image-guided brachytherapy compared with conventional brachytherapy.

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.

Tubular duplication of the oesophagus presenting with dysphagia.

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.