OBJECTIVE: This is a retrospective study aimed at clarifying the details of recurrence patterns and sites in patients with cervical cancer treated with definitive radiation therapy (RT). METHODS: Data were analyzed from consecutive patients, admitted to the University of Tokyo Hospital (Tokyo, Japan) between 2001 and 2013, who had received definitive RT, with or without chemotherapy, for International Federation of Gynecology and Obstetrics stages IB-IVA cervical cancer. RESULTS: One hundred and thirty-seven patients formed the patient cohort. The median follow-up period for surviving patients was 57.0 months. A complete response was achieved in 121 patients (88%). Of these, 36 (30%) developed a cancer recurrence during follow-up. The first sites of recurrence were located in intra-RT fields in nine, outside RT fields in 20, and both in seven patients. In the intra-RT field group, all patients showed a local recurrence, while no one experienced an isolated pelvic lymph node (PLN) recurrence. In the outside RT field group, the most frequent site of recurrence was lung (60%), and three-quarters of patients were free from intra-RT field recurrence until the last follow-up. Of the entire cohort, including 48 PLN-positive patients, only seven patients (5.1%) developed PLN persistence or recurrence, all in the common iliac, internal iliac, and/or obturator nodes, and all with another synchronous relapse. CONCLUSION: Local disease was a major type of intra-RT field recurrence, while PLN control was favorable even in initially PLN-positive patients. The predominance of outside RT field recurrence alone highlights issues concerning distant control, including the intensity enhancement of systematic therapy.
Adenocarcinoma/drug therapy/*radiotherapy/secondary ; Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents/therapeutic use ; Brachytherapy ; Carcinoma, Squamous Cell/drug therapy/*radiotherapy/secondary ; Chemoradiotherapy ; Disease-Free Survival ; Dose Fractionation ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms/*secondary ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Recurrence, Local/*diagnosis ; Pelvis ; Retrospective Studies ; Survival Rate ; Uterine Cervical Neoplasms/drug therapy/pathology/*radiotherapy

OBJECTIVE: To investigate the impact of pelvic radiation on survival in patients with uterine serous carcinoma (USC) who received adjuvant chemotherapy. METHODS: Patients with stage I-IV USC were identified from the Surveillance, Epidemiology, and End Results program 2000 to 2009. Patients were included if treated with surgery and chemotherapy. Patients were divided into two groups: those who received chemotherapy and pelvic radiation therapy (CT_RT) and those who received chemotherapy only (CT). Kaplan-Meier curves and Cox regression proportional hazard models were used. RESULTS: Of the 1,838 included patients, 1,272 (69%) were CT and 566 (31%) were CT_RT. Adjuvant radiation was associated with significant improvement in overall survival (OS; p<0.001) and disease-specific survival (DSS; p<0.001) for entire cohort. These findings were consistent for the impact of radiation on OS (p<0.001) and DSS (p<0.001) in advanced stage (III-IV) disease but not for early stage (I-II) disease (p=0.21 for OS and p=0.82 for DSS). In multivariable analysis adjusting for age, stage, race and extent of lymphadenectomy, adjuvant radiation was a significant predictor of OS and DSS for entire cohort (p=0.003 and p=0.05) and in subset of patients with stage III (p=0.02 and p=0.07) but not for patients with stage I (p=0.59 and p=0.49), II (p=0.83 and p=0.82), and IV USC (p=0.50 and p=0.96). Other predictors were stage, positive cytology, African American race and extent of lymphadenectomy. CONCLUSION: In USC patients who received adjuvant chemotherapy, adjuvant radiation was associated with significantly improved outcome in stage III disease but not for other stages. Positive cytology, extent of lymphadenectomy and African race were significant predictors of outcome.
Adult ; African Americans/statistics & numerical data ; Aged ; Aged, 80 and over ; Carcinoma, Papillary/pathology/radiotherapy/*therapy ; Chemoradiotherapy, Adjuvant ; Chemotherapy, Adjuvant ; Female ; Humans ; Hysterectomy ; *Lymph Node Excision ; Middle Aged ; Neoplasm Staging ; SEER Program ; Survival Rate ; Uterine Neoplasms/pathology/radiotherapy/*therapy

OBJECTIVE: Despite the rarity of uterine papillary serous carcinoma (UPSC) and uterine clear cell carcinoma (UCCC), they contribute disproportionately to endometrial cancer deaths. Sufficient clinical information regarding treatment and prognosis is lacking. The aim of this study is to evaluate treatment outcomes in a rare cancer cohort based on the experience at two tertiary care cancer centers. METHODS: Clinicopathologic data were retrospectively collected on 279 patients with UPSC and UCCC treated between 1995 to 2011. Mode of surgery, use of adjuvant treatment, and dissection of paraaoritc lymph nodes were evaluated for their association with overall survival (OS) and progression-free survival (PFS). RESULTS: 40.9% of patients presented with stage I disease, 6.8% of patients presented with stage II disease and 52.3% of patients presented with stages III and IV. Median follow-up was 31 months (range, 1 to 194 months). OS and PFS at 5 years were 63.0% and 51.9%, respectively. OS and PFS were not affected by mode of surgery (open vs. robotic approach; OS: hazard ratio [HR], 0.68; 95% confidence interval [CI], 0.28 to 1.62; PFS: HR, 0.78; 95% CI, 0.40 to 1.56). Adjuvant treatment was associated with improved OS in stages IB-II (HR, 0.14; 95% CI, 0.02 to 0.78; p=0.026) but not in stage IA disease. There was no difference in OS or PFS based on the performance of a paraaoritc lymph node dissection. CONCLUSION: Minimally invasive surgical staging appears a reasonable strategy for patients with non-bulky UPSC and UCCC and was not associated with diminished survival. Adjuvant treatment improved 5-year survival in stages IB-II disease.
Adenocarcinoma, Clear Cell/pathology/secondary/*therapy ; Aged ; Chemotherapy, Adjuvant ; Cystadenocarcinoma, Papillary/pathology/secondary/*therapy ; Cystadenocarcinoma, Serous/pathology/secondary/*therapy ; Female ; Humans ; Lymph Node Excision ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Staging ; Professional Practice ; Radiotherapy, Adjuvant ; Retrospective Studies ; Robotic Surgical Procedures ; Survival Analysis ; Treatment Outcome ; Uterine Neoplasms/pathology/*therapy

OBJECTIVETo investigate the clinical application of diffusion weighted imaging (DWI) in uterine cervical cancer and the apparent diffusion coefficient (ADC) value in diagnosis and predicting treatment response.

METHODSTwenty-eight patients with advanced primary cervical cancer confirmed by pathology and 10 cases of normal uterine cervix as control were recruited in this prospective clinical trial. To analyze the correlation between tumor volume measured in DWI and tumor maximum diameter measured according to the RECIST criteria. To compare the ADC value differences among the uterine cervical cancer, uterine myometrium, and normal uterine cervix. To compare the ADC values in 17 cancer patients before and after treatment.

RESULTSThe illustration of tumor boundary in DWI was superior to conventional T2WI and post-enhancement T1WI. The DWI with higher b value (2000 s/mm(2)) had a better signal-to-noise ratio. The tumor volume measured in DWI has good correlation with tumor maximum diameter according to RECIST criteria (r = 0.759, P < 0.01). When b = 800 s/mm(2), the ADC values of the uterine cervical cancer, uterine myometrium, and normal uterine cervix were (9.85 ± 1.55)×10(-3) mm(2)/s, (14.20 ± 2.80)×10(-3) mm(2)/s, and (14.14 ± 0.45) ×10(-3) mm(2)/s. When b = 2000 s/mm(2), the ADC values of the uterine cervical cancer, uterine myometrium and normal uterine cervix were (7.38 ± 0.98)×10(-3) mm(2)/s, (8.52 ± 2.38)×10(-3) mm(2)/s, and (8.60 ± 0.63)×10(-3) mm(2)/s, respectively. There were significant differences between the cervical cancer and normal cervix or uterine myometrium (P < 0.001 for both). When b = 800 s/mm(2), the ADC value was (9.85 ± 1.55)×110(-3) mm(2)/s before and (13.41 ± 2.93)×10(-3) mm(2)/s after treatment (P < 0.001). When b = 2000 s/mm(2), the ADC value was (7.38 ± 0.98)×10(-3) mm(2)/s before and (8.93 ± 1.92)×10(-3) mm(2)/s after treatment (P = 0.008). Univariate logistic regression analysis showed that 25% ADC, 50%ADC, and 75%ADC in the tumor ADC value histogram before treatment were significantly correlated to the treatment outcome of cervical cancer (P < 0.05 for all). Multivariate regression analysis showed that 25%ADC, 50%ADC, and 75%ADC in the tumor ADC value histogram before treatment were not significantly correlated to the treatment outcome of cervical cancer (P > 0.05 for all). The values of ROC curves were 25%ADC = 0.818, 50%ADC = 0.775, and 75%ADC = 0.716 (P > 0.05), however, the 25% ADC showed a relatively stronger statistical power.

CONCLUSIONSDWI helps to confirm the morphology and exact target zone of the tumor for radiotherapy. DWI volume measurement is well correlated with RECIST criteria, particularly in volume measurement of irregular tumors. ADC value has a potential in quantitatively monitoring treatment response and predicting outcome of cervical cancers.

Adenocarcinoma ; diagnosis ; drug therapy ; pathology ; radiotherapy ; Antineoplastic Agents ; therapeutic use ; Carcinoma, Squamous Cell ; diagnosis ; drug therapy ; pathology ; radiotherapy ; Case-Control Studies ; Cervix Uteri ; pathology ; Cisplatin ; therapeutic use ; Diffusion Magnetic Resonance Imaging ; Female ; Humans ; Middle Aged ; Myometrium ; pathology ; Prospective Studies ; ROC Curve ; Radiotherapy, Conformal ; Treatment Outcome ; Tumor Burden ; Uterine Cervical Neoplasms ; diagnosis ; drug therapy ; pathology ; radiotherapy

OBJECTIVETo explore the clinical value and efficacy of reduced field intensity modulated radiation therapy (RF-IMRT) for patients with advanced cervical cancer.

METHODSSeventy-one patients with stage IIB-IIIB cervical cancer, who underwent reduced field IMRT (RF-IMRT group) and 72 patients treated with conventional radiotherapy (c-RT group) in Shandong Cancer Hospital between 2005 August and 2011 August, were enrolled in this study. The RF-IMRT plans were as follows: whole pelvic IMRT plan was performed to deliver an initial dose of 30 Gy, then the irradiated volume was reduced to lymphatic drainage region as well as paracervix and parametrium for an additional 30 Gy boost. Conventional 2-field RT plan was performed in these patients using ADAC Pinnacle 3 planning system, to be given the same prescription dose, and to compare the irradiation dose of organs at risk (OARs). At the same time, conventional 2-field RT was performed in 72 patients of the c-RT group. Concurrent chemotherapy and intracavitary brachytherapy were also performed in the two groups. The treatment response, toxicities, normal tissue avoidance, and survival were assessed.

RESULTSSixty-six patients of the RF-IMRT group and 65 patients of the c-RT group fulfilled the treatment plan. IMRT plans yielded better dose conformity to the target (0.711 ± 0.057 vs. 0.525 ± 0.062, P = 0.032) and better sparing of the rectum, bladder and small intestine (rectum: 41.6 ± 6.8 vs. 50.8 ± 3.2, P = 0.016; bladder: 40.2 ± 2.9 vs. 51.4 ± 1.8, P = 0.007; small intestine: 22.3 ± 2.6 vs. 35.8 ± 3.9, P = 0.004). The mean dose delivered to the planning target volume (PTV) was significantly higher in the RF-IMRT group than that in the c-RT group (60.8 vs. 51.2 Gy, P = 0.006). The RF-IMRT patients experienced significantly lower acute and chronic toxicities with comparable short-term effects than did those treated with conventional RT (P > 0.05). No significant differences were found between the two groups for 1-, 3-, and 5-year overall survival (OS) rates, while a significantly higher progression-free survival (PFS, 65.2% vs. 46.2%, P = 0.031) rate was observed in the RF-IMRT group.

CONCLUSIONSRF-IMRT yields higher dose distributions and lower toxicities compared with conventional RT, and both the tumor target volume and pelvic lymphatic drainage region achieve curative dose irradiation, the adjacent organs at risk are well protected, and with tolerable adverse reactions. Yet, RF-IMRT provides comparable clinical outcomes and higher PFS.

Adenocarcinoma ; drug therapy ; pathology ; radiotherapy ; Brachytherapy ; Carcinoma, Squamous Cell ; drug therapy ; pathology ; radiotherapy ; Chemoradiotherapy ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Neoplasm Staging ; Organs at Risk ; Radiotherapy Dosage ; Radiotherapy Planning, Computer-Assisted ; Radiotherapy, Intensity-Modulated ; adverse effects ; methods ; Remission Induction ; Survival Rate ; Uterine Cervical Neoplasms ; drug therapy ; pathology ; radiotherapy

Adenocarcinoma ; drug therapy ; immunology ; pathology ; radiotherapy ; surgery ; Adult ; Antigens, Neoplasm ; metabolism ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Carboplatin ; administration & dosage ; Carcinoma, Squamous Cell ; drug therapy ; immunology ; pathology ; radiotherapy ; surgery ; Chemoradiotherapy, Adjuvant ; Chemotherapy, Adjuvant ; Female ; Humans ; Hysterectomy ; Iridium Radioisotopes ; therapeutic use ; Middle Aged ; Neoadjuvant Therapy ; methods ; Neoplasm Staging ; Paclitaxel ; administration & dosage ; Preoperative Period ; Radiotherapy, Adjuvant ; Retrospective Studies ; Serpins ; metabolism ; Treatment Outcome ; Uterine Cervical Neoplasms ; drug therapy ; immunology ; pathology ; radiotherapy ; surgery

OBJECTIVETo analyze the clinical characteristics, influencing factors and outcome of recurrent patients with early stage bulky cervical carcinoma.

METHODSBetween January 1(st) 2000 and December 31(st) 2009, 76 patients with stage Ib2 and IIa2 bulky cervical carcinoma developed recurrence and (or) metastasis. The recurrence time, recurrence location, recurrence-related factors, treatment and survival were analyzed.

RESULTSThe median follow up was 44 months (9-137 months). The overall recurrence and (or) metastasis rate was 22.6%. The 1-, 1-2, 3-5 and 5-year recurrence and (or) metastasis rates were 38.2%, 27.6%, 30.3% and 3.9%, respectively. The 5-year survival rate of local recurrence was 34.5%, that of distant metastasis was 23.6%, and that of distant metastasis with synchronous pelvic recurrence was 11.1%, (P = 0.555). The 5-year survival rate of patients who received surgery plus chemotherapy, radiation plus chemotherapy and chemotherapy alone after recurrence and (or) metastasis were 53.3%, 30.7% and 24.6%, respectively (P = 0.686). Univariate analysis demonstrated that tumor recurrence and (or) metastasis in patients of the stage Ib2 and IIa2 bulky cervical carcinoma were influenced by the disease stage, pelvic lymph node metastasis, deep cervical stromal invasion, lymphovascular tumor thrombus and pathological types. Multivariate regression analysis demonstrated that pelvic lymph node metastasis, lymphovascular tumor thrombus and pathological types were the key factors affecting the recurrence and (or) metastases of the stage Ib2 and IIa2 bulky cervical carcinoma. Subgroup analysis showed that pelvic lymph node metastasis and stage were the main factors affecting the local recurrence in those patients, and the pathological type, vascular tumor thrombus and pelvic lymph node metastasis were the main factors affecting the distant metastasis.

CONCLUSIONSRecurrence and(or) metastasis of early stage bulky cervical cancer are mostly happened within 2 years post operation. Patients with pelvic lymph node metastasis have high probability to develop local recurrence and distant metastasis. Patients with non-squamous cell carcinoma and lymphovascular tumor thrombus are more likely to develop distant metastasis. Neoadjuvant chemotherapy does not decrease local recurrence and distant metastasis in patients with stage Ib2 and IIa2 bulky cervical carcinoma. Individualized treatment is advised for recurrent patients.

Adenocarcinoma ; pathology ; secondary ; surgery ; therapy ; Carcinoma, Squamous Cell ; pathology ; secondary ; surgery ; therapy ; Chemotherapy, Adjuvant ; Female ; Follow-Up Studies ; Humans ; Hysterectomy ; Lung Neoplasms ; drug therapy ; secondary ; Lymph Node Excision ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; Multivariate Analysis ; Neoadjuvant Therapy ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local ; surgery ; therapy ; Neoplasm Staging ; Pelvis ; Radiotherapy, Adjuvant ; Survival Rate ; Tumor Burden ; Uterine Cervical Neoplasms ; pathology ; surgery ; therapy

OBJECTIVETo investigate the clinicopathological characteristics, histological diagnosis, immunohistochemistry and prognosis of cervical glassy cell carcinoma (GCC).

METHODSThe clinical characteristics, cytology, histology and immunohistochemistry were analyzed in 5 cases of GCC.

RESULTSThe average age of the five patients was 34.4 years (31 - 41 years). Abnormal vaginal bleeding and/or watery discharge were clinical presentations. One case was complicated with pregnancy and another one had a seven-year history of using contraceptives. All patients had an obvious mass in the cervix. Characteristic morphological features of GCC were present in 2 cases. Morphologically, the tumors consisted of clusters of tumor cells with distinct cell bounders, a large amount of eosinophilic granules in the cytoplasm imparting ground glass appearance, and thin nuclear membrane and prominent nucleoli. Nuclear enlargement and multinucleation were frequently noted. Mitosis and apoptosis were common. Numerous eosinophils and plasma cells were present in the stroma. Immunohistochemically, GCC expressed markers for both squamous cell carcinoma (p63 and CK34βE12) and adenocarcinoma (CAM5.2, MUC1, MUC2 and CEA). Ki-67 proliferation index was high (≥ 70%). All the five patients were treated with radical hysterectomy, followed by radiation and chemotherapy. The tumor-free survival time ranged from 25 days to 33 months.

CONCLUSIONSGCC is a distinct variant of adenosquamous carcinoma of the cervix with high proliferation index and expression of markers of both squamous cell carcinoma and adenocarcinoma. The tumor has characteristic cytological and histological features.

Adult ; Biomarkers ; metabolism ; Carcinoembryonic Antigen ; metabolism ; Carcinoma, Adenosquamous ; metabolism ; pathology ; therapy ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Female ; Humans ; Hysterectomy ; methods ; Immunohistochemistry ; Keratins ; metabolism ; Ki-67 Antigen ; metabolism ; Membrane Proteins ; metabolism ; Mucin-1 ; metabolism ; Pregnancy ; Pregnancy Complications, Neoplastic ; metabolism ; pathology ; therapy ; Radiotherapy, Adjuvant ; Uterine Cervical Neoplasms ; metabolism ; pathology ; therapy

OBJECTIVETo investigate the early efficacy of nedaplatin combined with megestrol in concurrent chemoradiotherapy for advanced cervical cancer.

METHODSForty-two cases of cervical cancer (FIGO IIb to IVa) were divided randomly into two groups: radiotherapy alone (21 cases) and radiation plus chemotherapy (Nedaplatin) group. The same radiotherapy was given to the two groups. Patients of the RT + C group received nedaplatin 30 mg/m2 in intravenous drip infusion once weekly on day 1, for 4 to 5 weeks, and megestrol 160 mg orally every day during the radiation therapy.

RESULTSThe early outcome: the complete remission rate was 81.0% and partial remission rate was 19.0% in the RT + C group, significantly better than the CR (38.1%) and PR (42.9%) in the RT group. The 1-year survival rates in the two groups were 100% (21/21) and 81.0% (17/21), respectively, with a significant difference between the two groups (P<0.05).

CONCLUSIONSThe combination of nedaplatin and megestrol with concurrent chemoradiotherapy can improve the early outcome of advanced cervical cancer, with somewhat increased but tolerable adverse effects.

Adenocarcinoma ; drug therapy ; pathology ; radiotherapy ; Adult ; Alopecia ; chemically induced ; Anemia ; chemically induced ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Brachytherapy ; Chemoradiotherapy ; adverse effects ; Diarrhea ; chemically induced ; Female ; Follow-Up Studies ; Humans ; Iridium Radioisotopes ; therapeutic use ; Leukopenia ; chemically induced ; Megestrol ; administration & dosage ; Middle Aged ; Neoplasm Staging ; Organoplatinum Compounds ; administration & dosage ; Particle Accelerators ; Radiotherapy, High-Energy ; Remission Induction ; Survival Rate ; Thrombocytopenia ; chemically induced ; Uterine Cervical Neoplasms ; drug therapy ; pathology ; radiotherapy

BACKGROUND AND OBJECTIVEIn the past decade, no remarkable improvement has been made in the 5-year survival of cervical cancer patients. This study was to explore the influence of lymph vascular space invasion (LVSI) on the prognosis of patients with early-stage cervical squamous cell carcinoma.

METHODSA total of 111 eligible patients with FIGO stage IB and IIA cervical squamous cell carcinoma underwent radical hysterectomy and pelvic lymphadenectomy at Sun Yat-sen University Cancer Center between January 1995 and December 2002. The histopathological slides of the 111 patients were reviewed by a senior gynecological pathologist. LVSI, invasion depth, tumor differentiation and lymph node metastasis were evaluated.

RESULTSLVSI was present in 62 patients. The univariate analysis showed that the risk factors of overall survival (OS) included positive LVSI (P = 0.019) and lymph node metastasis (P = 0.002), while the risk factors of progression-free survival (PFS) included LVSI (P = 0.029), lymph node metastasis (P = 0.002), SccAg value (P = 0.018), invasion depth (P = 0.022) and positive surgical margin (P = 0.002). The multivariate analysis showed that lymph node metastasis was the independent prognostic factor of OS (P = 0.015), while lymph node metastasis and positive surgical margin were the independent factors of PFS (P = 0.006, P = 0.006). LVSI was correlated with lymph node metastasis (P = 0.011).

CONCLUSIONWhether LVSI is an independent prognostic factor of early-stage cervical squamous cell carcinoma cannot be determined currently while LVSI is a risk factor of metastasis and relapse.

Adult ; Aged ; Carcinoma, Squamous Cell ; pathology ; therapy ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Hysterectomy ; methods ; Lymph Node Excision ; Lymph Nodes ; pathology ; surgery ; Lymphatic Metastasis ; Lymphatic Vessels ; pathology ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Pelvis ; Proportional Hazards Models ; Radiotherapy, Adjuvant ; Retrospective Studies ; Uterine Cervical Neoplasms ; pathology ; therapy