Chemoradiation Therapy For Cervical Cancer Research Articles

Alum instillation: A management option for intractable hemorrhagic cystitis

Intractable hemorrhagic cystitis is an uncommon but significant treatment complication of concurrent chemoradiation therapy for cervical cancer. Alum instillation is regarded as a safe and effective option for its treatment. This case presentation will discuss a patient who presented with postradiation cystitis and was treated with alum irrigation. The aim of this report is to offer alum irrigation as a management option for intractable hematuria.

Clinical Significance of Arginine Signaling in Patients with Cervical Cancer Receiving Cisplatin Chemoradiation Therapy

Many human malignancies do not produce sustainable amounts of arginine (Arg) because the rate-limiting enzyme, arginosuccinate synthetase 1 (ASS1), in the biosynthesis of Arg has been silenced. We investigated the clinical significance of ASS1 expression on cisplatin chemoradiation therapy for cervical cancer. A total of 118 consecutive patients with FIGO stages IB to IVA cervical cancer who had received platinum-based concurrent chemoradiotherapy were identified and their clinical courses were reviewed. Immunohistochemical studies were performed on their formalin-fixed, paraffin-embedded tissues. The prognostic value of ASS1 was investigated by performing univariate and multivariate analyses on factors affecting patient survival. Median follow-up for all patients was 5.5 years (range: 1 to 23.5 years). Overexpression of ASS1 was an independent prognostic factor. The 5-year disease-free survival for patients with ASS1-positive tumors was 72.3%, compared with 51.6% for patients with ASS1-negative tumors (P = 0.02). Univariate Cox proportional hazards models showed positive ASS1 immunostaining (hazard ratio [HR]: 0.50, 95% CI: 0.28-0.90), FIGO stage (HR: 0.33, 95% CI: 0.18-0.59) and brachytherapy (HR: 0.22, 95% CI: 0.10-0.48) were significant prognostic factors affecting disease-free survival. In multivariate analyses, positive ASS1 remained an independent significant prognostic factor for DFS (HR = 0.45, 95% CI: 0.25-0.83). Overexpression of ASS1 is an independent prognostic factor for cervical cancer patients receiving cisplatin concurrent chemoradiotherapy.

Patterns of Relapse After Adjuvant Chemoradiation for Cervical Cancer in a Phase 3 Clinical Trial (PARCER): An Evaluation of Updated NRG Oncology/RTOG Target Delineation Guidelines

The Radiation Therapy Oncology Group (RTOG) under NRG Oncology recently published updated contouring guidelines for intensity modulated radiation therapy in postoperative treatment for endometrial and cervical cancer. The present study was designed to evaluate the implications ofnewly published guidelines. We recruited 300 patients in a phase 3 randomized controlled trial of adjuvant chemoradiation therapy for cervical cancer (NCT01279135) to understand patterns of relapse. For those patients with pelvic relapse, we imported radiation therapy structure sets, treatment plans, and diagnostic images atrelapse on the treatment planning system. We performed rigid registration with treatment planning images that contained the delineated planning target volume and radiation dose information. We delineated gross tumor volume at time of relapse on the diagnostic scans and superimposed it on the radiation therapy treatment scans. We categorized the site of pelvic relapse as "within field of old RTOG/[Postoperative Adjuvant Radiation in Cervical Cancer (PARCER)] target delineation guidelines" or "within field of new NRG/RTOG guidelines," or both, and compared proportions of recurrences contained within the 2 guidelines. We consider a P value of <.05 statistically significant. Additionally, we generated intensity modulated radiation therapy treatment plans based on the new guidelines for a limited set of patients to see if these new guidelines increased the organ at risk doses. Most common form of relapse was distant metastasis (15%). Pelvic relapse rate in our study was 8%. Overall, 9 out of 19 relapses were encompassed in the contouring guidelines of the old RTOG/ Postoperative Adjuvant Radiation in Cervical Cancer (PARCER) trial, and 12 out of 19 were encompassed within the new RTOG 2021 contouring guidelines. This corresponded to a further 1% reduction in local relapses (P=.007). Dose to rectum was marginally increased with the new contouring, with no difference in other organs at risk. Salvage treatment was offered in 25 out of 60 patients who relapsed. Patients who received local treatment after relapse had a mean survival after relapse of 27.2 months compared with 8 months among those who received supportive care alone. Our study supportsthe use of newly published NRG/RTOG contouring guidelines in patients with cervical cancer who have undergone hysterectomy. Further data are needed to ascertain if anterior extension of the clinical target volume is needed as in the Postoperative Adjuvant Radiation in Cervical Cancer trial.

Relationship of irradiated bone marrow volume and neutropenia in patients undergoing concurrent chemoradiation therapy for cervical cancer.

Concurrent chemoradiation therapy (CCRT) is the standard of care in the management of cervical cancer (International Federation of Gynecology and Obstetrics [FIGO] 2008 Stages IB2-IVA). Apart from the myelotoxic effects of chemotherapy, irradiation of pelvic bone marrow (BM) in the radiation field, can also contribute to hematological toxicity. We examined the relationship of irradiated BM volume and neutropenia in cervical cancer patients undergoing CCRT. This prospective study was conducted in a tertiary cancer center with a longitudinal study design. A total of 43 patients undergoing CCRT for cervical cancer were included. Using auto bone segmentation, the external contour of pelvic bones from L4 vertebral body to ischial tuberosities were delineated as BM. The volume of BM receiving 10, 20, 40, 50 Gy was calculated. Complete blood counts were done weekly to evaluate the neutropenia and were graded according to Common Terminology Criteria for Adverse Events, version 3.0. The risk of developing neutropenia was analyzed using logistic regression. Twenty-seven patients (62.8%) received 5 cycles of chemotherapy, 14 patients (32.6%) received 4 cycles of chemotherapy and 2 patients (4.7%) received 3 cycles of chemotherapy. Overall, 22 patients (51.2%) experienced acute neutropenia. On multivariate analysis increased BM V50Gy had a statistically significantly odds of developing any grade of neutropenia (odds ratio [OR] =1.43; 95% confidence interval [CI], 1.03-1.97; P = 0.028). When comparing patients receiving BM V40Gy ≥40% with BM V40Gy <40% odds of any grade of neutropenia was increased (OR = 2.03; 95% CI, 0.55-7.42; P = 0.28). Moreover, when comparing patients receiving BM V50Gy ≥15% with BM V50Gy <15% odds of any grade of neutropenia was increased (OR = 2.13; 95% CI, 0.57-7.97; P = 0.26). High-dose irradiation to the larger volume of BM prevents compensatory hyperplasia which leads to neutropenia in patients undergoing CCRT for cervical cancer.

Effect of GSDMB polymorphism on sensitivity to chemoradiation therapy for cervical cancer

Effect of GSDMB polymorphism on sensitivity to chemoradiation therapy for cervical cancer

Microbial Diversity and Composition Is Associated with Patient-Reported Toxicity during Chemoradiation Therapy for Cervical Cancer

Patients receiving pelvic radiation for cervical cancer experience high rates of acute gastrointestinal (GI) toxicity. The association of changes in the gut microbiome with bowel toxicity from radiation is not well characterized. Thirty-five patients undergoing definitive chemoradiation therapy (CRT) underwent longitudinal sampling (baseline and weeks 1, 3, and 5) of the gut microbiome and prospective assessment of patient-reported GI toxicity. DNA was isolated from stool obtained at rectal examination and analyzed with 16S rRNA sequencing. GI toxicity was assessed with the Expanded Prostate Cancer Index Composite instrument to evaluate frequency, urgency, and discomfort associated with bowel function. Shannon diversity index was used to characterize alpha (within sample) diversity. Weighted UniFrac principle coordinates analysis was used to compare beta (between sample) diversity between samples using permutational multivariate analysis of variance. Linear discriminant analysis effect size highlighted microbial features that best distinguish categorized patient samples. Gut microbiome diversity continuously decreased over the course of CRT, with the largest decrease at week 5. Expanded Prostate Cancer Index Composite bowel function scores also declined over the course of treatment, reflecting increased symptom burden. At all individual time points, higher diversity of the gut microbiome was linearly correlated with better patient-reported GI function, but baseline diversity was not predictive of eventual outcome. Patients with high toxicity demonstrated different compositional changes during CRT in addition to compositional differences in Clostridia species. Over time, increased radiation toxicity is associated with decreased gut microbiome diversity. Baseline diversity is not predictive of end-of-treatment bowel toxicity, but composition may identify patients at risk for developing high toxicity.

Comparing survival outcomes between surgical and radiographic lymph node assessment in locally advanced cervical cancer: A propensity score-matched analysis

ObjectiveTo investigate progression-free survival (PFS) and overall survival (OS) between women who underwent surgical versus radiographic assessment of pelvic lymph nodes (PLN) and para-aortic lymph nodes (PALN) prior to chemoradiation therapy for cervical cancer. MethodsIn this retrospective cohort analysis, patients with stage IB2 - IIIB squamous cell, adenocarcinoma and adenosquamous carcinoma of the cervix who completed concurrent chemoradiation therapy (CCRT) between 2000 and 2017 from the Mayo Clinic Cancer Registry were identified. A 1:2 propensity score matching between surgical and imaging groups was performed and PFS and OS were compared between groups. Results148 patients were identified and after propensity score matching, 35 from the surgical group and 70 from the imaging group were included in the analysis. There were no statistical differences in baseline characteristics between the 2 groups. The median follow-up time was 41 months (range 7–218) for the surgical group and 51.5 months (range 7–198) for the imaging group. Five-year PFS was 62.6% for the surgical group and 72.4% in imaging group (HR 1.11, 95% CI 0.54–2.30, p = 0.77). Five-year OS was 70.2% for the surgical group and 70.5% for the imaging group (HR 1.02, 95% CI 0.46–2.29, p = 0.96). FIGO stage, PALN metastasis, and parametrial involvement were found to be poor prognosticators for PFS and OS in univariate analysis. Only PALN metastasis significantly predicted unfavorable PFS (HR 2.76, 95% CI 1.23–6.18, p = 0.01) and OS (HR 3.46, 95% CI 1.40–8.55, p = 0.01) in multivariate analysis. There were no differences in locoregional recurrence and distant metastasis between the two groups (p = 0.33 and 0.59 respectively). ConclusionPatients with cervical cancer who underwent radiographic assessment of PLN and PALN had comparable survival outcomes to surgical assessment.

Change in Patterns of Failure After Image-Guided Brachytherapy for Cervical Cancer: Analysis From the RetroEMBRACE Study

Image guided adaptive brachytherapy (IGABT) for cervical cancer improves pelvic control and survival across all stages. Improvement in pelvic control is larger in advanced stages, but improvement in survival is similar across stages. This paper analyzes the patterns of failure in the RetroEMBRACE cohort to investigate this discrepancy. 731 patients from 12 institutions treated with chemoradiation therapy and magnetic resonance imaging or computed tomography-based IGABT were evaluated. The pattern of failure at time of first relapse was analyzed. Three hundred twenty-five failures (single and synchronous) occurred in 222 of 731 patients (30%). Among the 325 failures, 9% were local and 6% regional. Pelvic (local or regional) failures made up 13%, paraaortic node (PAN) 9%, systemic 21%, and distant (systemic+PAN) 24%. Of the 222 patients with treatment failure, 21% had pelvic failure alone, 57% had distant failure alone, and 23% had both pelvic and distant failure. Of all failures that occurred, 40% to 50% occurred in the first year, with a further 20% to 30% occurring in the second year. Although local, regional, and PAN failure tended to plateau after year 3, systemic failure continued to occur up to year10. Implementation of IGABT has changed the patterns of relapse after chemoradiation therapy for cervical cancer. The predominant failure after IGABT is systemic, whereas the predominant failure with conventional brachytherapy is pelvic. Effective treatments to eradicate micrometastases in PAN and distant organs are needed in addition to IGABT and chemoradiation therapy to maximize local, regional, PAN, and systemic control and improve survival.

Impact of GSTM1, GSTT1 and GSTP1 genes polymorphisms on clinical toxicities and response to concomitant chemoradiotherapy in cervical cancer

ABSTRACTBackground: Certain forms of chemoradiotherapy generate toxic reactive oxygen species, which may be ameliorated by antioxidant enzymes such as glutathione S-transferase (GST). Genetic polymorphisms of GST may predict treatment outcomes and can be used as genetic marker to screen patients before treatment. We hypothesised an effect of GST polymorphisms on the response and toxicities produced by chemoradiation therapy.Materials and methods: GST polymorphisms were determined by multiplex polymerase chain reaction and PCR-restriction fragment length polymorphism (PCR-RFLP) in 227 women with cervical cancer receiving cisplatin based chemoradiotherapy. Treatment response and toxicities were evaluated by standard internationally recognised criteria (RECIST and RTOG).Results: Severe (grade 3–4) gastrointestinal and haematological toxicities were present in 22 (9.4%) and 16 (7.0%) patients, respectively. GSTM1 null, GSTT1 null and GSTP1 AG genotypes brought marginally better non-significant associations. In single locus analysis GSTP1 AG and GG was linked to greatest risk of severe (grade 3–4) gastrointestinal toxicity (OR = 3.12, P = 0.035 and OR = 6.99, P = 0.01, respectively). In gene–gene interaction analysis, GSTM1 null-GSTP1 GG showed 4.2-fold higher risk of severe gastrointestinal toxicity (P = 0.014). GSTT1 null-GSTP1 AG reached statistical significance with a 3.9-fold higher risk of high grade gastrointestinal toxicity (P = 0.038).Conclusions: Although no significant links were found between GST polymorphism and treatment response, null genotypes of GSTM1, GSTT1 and ‘G’ allele of GSTP1 bring a higher risk of severe gastrointestinal toxicity due to chemoradiation therapy in cervical cancer.

Adjuvant Chemoradiation Therapy for Cervical Cancer and Effect of Timing and Duration on Treatment Outcome

Worse treatment outcomes can be expected with prolongation of the overall treatment time (OTT) during definitive chemoradiation therapy (CRT) for cervical cancer. In the adjuvant setting, data on the relative importance of the OTT and the importance of RT and chemotherapy synchronization are scarce. Using the National Cancer Database, we evaluated the effect of these treatment variables on overall survival in the adjuvant CRT setting. The present analysis included nonmetastatic cervical cancer patients undergoing hysterectomy followed by adjuvant CRT. The proportional hazard model was used to estimate the effect of prognostic factors (age, comorbidity, race, tumor size, tumor grade, tumor histologic type, number of high-risk pathologic factors) and time-related variables (surgery to RT start interval [SR], OTT [RT start to end dates], package time [from diagnosis date to CRT end date] and optimum CRT synchronization [whether chemotherapy and RT start dates coincided]) on survival. Of 3051 patients, 60% finished RT within 7weeks and 85% received optimum CRT. Among other factors, univariate analysis identified longer OTT (hazards ratio [HR] 1.33; P<.001), longer SR (HR 1.17; P=.05), and nonoptimum CRT timing (HR 1.21; P=.04) as poor prognosticators. Of these factors, SR (HR 1.20; P=.04) and OTT (HR 1.21; P=.002) retained significance on multivariate analysis. An OTT >7weeks remained a significant factor even after propensity score matching (P=.04). The results of our analysis suggest that prolongation of the adjuvant CRT duration >7weeks is associated with poor survival and SR of <8weeks should be attempted whenever clinically feasible.

Prognostic Utility of Pretreatment Hematologic Parameters in Patients Receiving Definitive Chemoradiation Therapy for Cervical Cancer

Prognostic Utility of Pretreatment Hematologic Parameters in Patients Receiving Definitive Chemoradiation Therapy for Cervical Cancer

Standardized Spatial Heterogeneity of Baseline Intratumoral 18F-FDG Accumulation for Outcome Prediction of Concurrent Chemoradiation Therapy in Cervical Cancer

Standardized Spatial Heterogeneity of Baseline Intratumoral 18F-FDG Accumulation for Outcome Prediction of Concurrent Chemoradiation Therapy in Cervical Cancer

Prognostic Significance of Tumor Response as Assessed by Sequential 18F-Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography During Concurrent Chemoradiation Therapy for Cervical Cancer

To investigate the prognostic role of metabolic response by the use of serial sets of positron emission tomography/computed tomography (PET/CT) in patients with cervical cancer who were treated with concurrent chemoradiation therapy (CCRT). A total of 60 patients who were treated with CCRT between February 2009 and December 2010 were analyzed. Three sequential PET/CT images were acquired for each patient: pre-CCRT, during-CCRT at 4 weeks of CCRT, and 1 month post-CCRT PET/CT. Metabolic responses were assessed qualitatively. The percentage changes in the maximum values of standardized uptake value (ΔSUV(max)%) from the PET/CT images acquired pre-CCRT and during-CCRT were calculated. Receiver operating characteristic (ROC) curve analysis was performed to evaluate whether ΔSUV(max)% could predict complete response (CR) on the post-CCRT PET/CT and to identify the best cutoff value. Prognostic factors of progression-free survival (PFS) were analyzed. During-CCRT PET/CT showed that 8 patients (13%) had CR, and the other 52 patients (87%) had partial response (PR). On the post-CCRT PET/CT, 43 patients (73%) had CR, 12 patients (20%) had PR, and 4 patients (7%) had progressive disease. The average SUV(max) in primary tumors was 16.3 (range, 6.4-53.0) on the pre-CCRT PET/CT images and 5.3 (range, 0-19.4) on the during-CCRT PET/CT images. According to ROC curve analysis, ΔSUV(max)% could predict CR response on post-CCRT PET/CT (P<.001, cutoff value of 59.7%). In all patients, the PFS rate was 71.9% at 2 years. Multivariate analysis showed that ΔSUV(max)% ≥60% (P=.045) and CR response on the post-CCRT PET/CT (P=.012) were statistically significant predictors of PFS. Metabolic responses on the during-CCRT images at 4 weeks of treatment and 1-month post-CCRT PET/CT images may predict treatment outcomes in patients with cervical cancer. ΔSUV(max)% ≥60% at 4 weeks of CCRT may predict CR response on 1-month post-CCRT PET/CT and also PFS.

MO-A-137-04: Robustness of Bone Marrow Sparing in Intensity Modulated Proton Therapy for Cervical Cancer

Purpose: To determine the effectiveness of pelvic bone marrow sparing by utilizing intensity modulated proton therapy (IMPT) in the treatment of cervical cancer, in comparison to that of intensity modulated photon therapy (IMXT); and to investigate the robustness of the bone marrow sparing by IMPT under range uncertainty and patient setup uncertainty. Methods: 3-field IMPT was planned for five enrolled patients. DVH objectives for PTV and organs-at-risk (OAR) aimed to give 45 Gy to the tumor in 25 fractions, matching those of the IMXT plan delivered clinically. The percentage volumes of bone marrow receiving 10 Gy and 20 Gy were set to be reduced in IMPT compared with IMXT. The dose from the IMPT plan was then recalculated in uncertainty scenarios which were combinations of systematic 3% density errors and uniformly random patient setup errors of (0.6cm, 0.6cm, 0.6cm). The robustness of target coverage and bone marrow sparing through the whole course of 25 fractions was then analyzed. Results: In the static scenario, the IMPT plan achieved the same or better PTV coverage and OAR sparing compared to IMXT, and reduced the percentage volume of bone marrow receiving 15 Gy or larger dose (V15Gy) to 32.3% from 60.0% on average. Robustness analysis showed that proper CTV coverage is preserved over the whole course of treatment with the presumed range and positioning errors. The reduction of bone marrow dose is also statistically significant and robust under those uncertainties, with a minimum reduction of V15Gy to 39.9% from 60.0%. Conclusion: IMPT can significantly reduce the volume of active bone marrow receiving low dose radiation, therefore potentially decreasing hematologic toxicity in concurrent chemoradiation therapy for cervical cancer. Bone marrow sparing by IMPT is robust in the context of range and positioning uncertainties.

Concurrent chemoradiation therapy in cervical cancer: Prognostic factors, toxicity, and long-term survival in a center of reference for gynecologic cancer.

e16539 Background: Concurrent chemoradiation therapy has been the standard treatment in locally advanced cervical cancer since 1999, and our institution is a centre of reference for treatment of this pathology. Methods: In a homogeneous series of 288 patients treated between 1996 and December 2011, survival data, prognostic factors and toxicity of the treatment have been analyzed. The treatment includes external beam radiotherapy, concurrent weekly chemotherapy and brachytherapy. Results: Median age of the patients is 54 years old, and the FIGO classification for disease stages shows 14.6% IB2, 47.1% IIB, 24.4% III, and 7.8% IVA. Squamous cell carcinoma (77.4%) and adenocarcinoma (16.8%) are the most common histologies. After a median follow-up of 4.4 years, the 5-year overall survival rate is 80.2%. Classified by diagnostic stage, they are 85% in IB2, 76% in IIB, 70% in III, and 68% in IVA. The main location for recurrence is cervix (11.8%), and the most common site for distant disease is lung (4.8%). For patients with disease progression, 24.4% have local and distant recurrence. After local recurrence, radical surgery with pelvic exenteration was practised in 6 cases, 5 of them are still alive. In the multivariate analysis, the prognostic factors for overall survival that have been identified with a statistical significance, are HPV and HIV infection, high stages of disease and older patients. Performance status ≥1 and brachytherapy have only a significant value in the univariate analysis. The acute toxicity grade ≥3 was observed in 19.4% of patients (14.1% haematological). The most frequent low grade toxicity was 46.3% haematological, 40% of bowel-related toxicity, 38.9% of nausea and vomiting, and 8.1% of renal dysfunction. Chronic toxicity grade ≥3 has been only seen in 1.2% of patients (renal dysfunction), and in the low grades, it is a 6% of bowel-related toxicity and 1.4% of mild renal dysfunction. Conclusions: This long follow-up series shows a good overall survival rate with chemoradiation therapy in locally advanced stages of cervical cancer, with a low rate of acute and, especially, chronic toxicity, indicating a good quality of life for these patients.

Effects of Treatment Duration During Concomitant Chemoradiation Therapy for Cervical Cancer

To determine whether extended treatment duration (TD) impacts in-field relapse and survival in the setting of concomitant chemoradiation therapy (CRT) for cervical cancer. A total of 480 consecutive cervical cancer patients treated with radiation therapy (RT) alone or concomitant CRT for curative intent were retrospectively analyzed. Relapse was defined as in-field with respect to external beam radiation therapy fields. The effects of TD on in-field relapse, disease-free survival (DFS), and overall survival (OS) rates were assessed continuously and categorically within the separate RT and CRT cohorts. Covariates included age, histology, stage, and cumulative dose to point A. In-field relapse, DFS, and OS rates were estimated with Kaplan-Meier analysis; comparisons used log-rank statistic. Multivariate analysis used the Cox proportional hazards model. A total of 372 patients (RT n=206, CRT n=166) were evaluable, with a median follow-up for relapse-free patients of 4.2 years (RT 4.4 years, CRT 4.2 years; P=.807). Treatment duration was longer in the RT cohort (median 55 days; range 35-99 days) versus the CRT cohort (median 51 days; range 35-92 days) (P=.001). In the RT cohort, TD ≥62 days trended to significance for predicting inferior DFS (hazard ratio 1.42, 95% confidence interval 0.86-1.98, P=.086). However, in the CRT cohort, TD assessed continuously or categorically across multiple cutoff thresholds did not predict for in-field relapse, DFS, or OS. With RT alone, extended TD ≥62 days may adversely impact treatment efficacy. With the addition of concomitant chemotherapy to RT, however, extended TD has no effect on treatment efficacy.

A peculiar presentation: For 2 women, a rare infection preceded a more urgent diagnosis

A copious watery vaginal discharge was the symptom in 2 similar, although unusual cases. The first patient, a 51-year-old woman, also reported that the discharge was bloody. Twelve years earlier, she had undergone surgery and chemoradiation therapy for cervical cancer. Three years later, she had laser ablation for vaginal intraepithelial neoplasia grade 2. She was then lost to follow-up evaluation until 6 months before her current admission, when she sought treatment for the vaginal exudate. A biopsy identified colonies of Actinomyces species, and she was treated with penicillin.

Variable uterine uptake of FDG in adenomyosis during concurrent chemoradiation therapy for cervical cancer

To avoid improper tumor volume contouring in radiation therapy (RT) and other invasive procedures, we report a case of uterine adenomyosis showing increased 18F-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET)/computed tomography (CT) mimicking malignant tumor in a 44-year-old woman during concurrent chemoradiation therapy (CCRT) for uterine cervical cancer. The adenomyosis was not associated with her menstrual cycle or with normal endometrium uptake, and it resolved one month after completion of RT. This case indicates that uterine adenomyosis in a premenopausal woman may show false positive uptake of 18FDG-PET/CT associated with CCRT.

A case of primary retroperitoneal undifferentiated endometrial stromal sarcoma after concurrent chemoradiation therapy for cervical cancer

Endometrial stromal sarcoma (ESS) is a relatively rare uterine sarcoma, especially extrauterine ESS. Furthermore, retroperitoneal ESS are extremely rare. Up to now, there are only four cases of primary retroperitoneal ESS reported in the literature. We report one case of primary retroperitoneal undifferentiated endometrial stromal sarcoma after concurrent chemoradiation therapy for cervical cancer with a brief review of the literature.

Neuropilin‐1 expression identifies a subset of regulatory T cells in human lymph nodes that is modulated by preoperative chemoradiation therapy in cervical cancer

We examined the phenotype and function of CD4+ T cells expressing the semaphorin III receptor neuropilin-1 (Nrp1) in human lymph nodes and peripheral blood. In lymph nodes, Nrp1 identified a small regulatory CD4+ CD25(high) T-cell subpopulation (Nrp1+ Treg) that expressed higher levels of Forkhead box P3 (Foxp3) message and protein than Nrp1- Treg, and various molecular markers of activated Treg, i.e. CD45RO, human leucocyte antigen (HLA)-DR and glucocorticoid-induced tumour necrosis factor receptor (GITR). Similarly to conventional Treg, Nrp1+ Treg proliferated poorly in vitro, and exerted contact-dependent in vitro suppression of T-cell proliferation and cytokine secretion. However, Nrp1+ Treg were more efficient than Nrp1- Treg at inducing suppression. Nrp1 was also expressed on a small subpopulation of CD25(int) and CD25- CD4+ T cells that expressed more Foxp3, CD45RO, HLA-DR and GITR than their Nrp1- counterparts. In contrast, in peripheral blood Nrp1 identified a minor CD4+ T-cell subset that did not display the phenotypic features of Treg lacking Foxp3 expression and marginally expressing CD25. Hence, the function of Nrp1+ CD4+ T cells seemingly depends on their anatomical location. In a previous report, we proposed that Treg may curb the anti-tumour T-cell response in cervical cancer. We show here that Treg and Nrp1+ Treg levels dropped in the tumour-draining lymph nodes of patients with cervical cancer following preoperative chemoradiotherapy in a direct relationship with the reduction of tumour mass, suggesting that suppressor cell elimination facilitated the generation of T cells mediating the destruction of the neoplastic cells left behind after cytotoxic therapy.