Chemoradiation In Cervical Cancer Patients Research Articles

Magnesium Imbalance before and during Concomitant Chemoradiation in Cervical Cancer Patients: A Prospective Interventional Study

Introduction: Cervical cancer is a major health concern, especially in developing countries. It is the second most common cancer among women in India, largely due to limited access to advanced screening and Human Papilloma Virus (HPV) vaccination. Despite significant advancements in cervical cancer prevention and treatment, the disease remains a major health burden, particularly in low-resource settings. Magnesium (Mg), an essential mineral involved in immune function, inflammation and Deoxyribonucleic Acid (DNA) repair, has been linked to various cancers, including colorectal and breast cancers, but its role in cervical carcinoma is underexplored. Aim: To investigate the association between magnesium levels and cervical carcinoma and to explore the association of hypomagnesemia with concomitant chemotherapy using cisplatin during chemoradiation. Materials and Methods: This was a hospital-based prospective interventional study, in which a total of 322 subjects were included in the study, of which 161 were healthy controls and 161 were diagnosed cases of cervical carcinoma. The magnesium levels were estimated before and after treatment using the Xylidyl blue complexing method on an autoanalyser. The data were compared between the two groups using appropriate statistical analysis with Statistical Package for the Social Sciences (SPSS) software version 20.0. Results: The mean magnesium levels were 2.08±0.24 mg/ dL in controls and 1.56±1.02 mg/dL in cancer patients (p-value<0.001). Mean serum levels decreased in cancer patients postchemoradiation to 0.74±0.39 mg/dL. During concomitant chemoradiation with cisplatin, hypomagnesemia was observed as grade I in 62 (38.5%), grade II in 25 (15.5%), grade III in 12 (7.5%) and grade IV in 36 (22.4%). A significant correlation was found between hypomagnesemia and hyponatremia, hypokalemia and cumulative cisplatin dose toxicity. Conclusion: The study demonstrated a high prevalence of hypomagnesemia in cervical cancer patients, especially those undergoing cisplatin-based chemotherapy, with levels declining further during treatment. Routine magnesium monitoring and proactive management are essential to prevent complications and improve outcomes.

Using Radiomics and Machine Learning Applied to MRI to Predict Response to Neoadjuvant Chemotherapy in Locally Advanced Cervical Cancer.

Neoadjuvant chemotherapy plus radical surgery could be a safe alternative to chemo-radiation in cervical cancer patients who are not willing to receive radiotherapy. The response to neoadjuvant chemotherapy is the main factor influencing the need for adjunctive treatments and survival. In the present paper we aim to develop a machine learning model based on cervix magnetic resonance imaging (MRI) images to stratify the single-subject risk of cervical cancer. We collected MRI images from 72 subjects. Among these subjects, 28 patients (38.9%) belonged to the "Not completely responding" class and 44 patients (61.1%) belonged to the 'Completely responding' class according to their response to treatment. This image set was used for the training and cross-validation of different machine learning models. A robust radiomic approach was applied, under the hypothesis that the radiomic features could be able to capture the disease heterogeneity among the two groups. Three models consisting of three ensembles of machine learning classifiers (random forests, support vector machines, and k-nearest neighbor classifiers) were developed for the binary classification task of interest ("Not completely responding" vs. "Completely responding"), based on supervised learning, using response to treatment as the reference standard. The best model showed an ROC-AUC (%) of 83 (majority vote), 82.3 (mean) [79.9-84.6], an accuracy (%) of 74, 74.1 [72.1-76.1], a sensitivity (%) of 71, 73.8 [68.7-78.9], and a specificity (%) of 75, 74.2 [71-77.5]. In conclusion, our preliminary data support the adoption of a radiomic-based approach to predict the response to neoadjuvant chemotherapy.

The tolerance to chemoradiation for cervical cancer patients: A comparative prospective study of rural versus urban population.

Rural versus urban cervical cancer. This study aims to study the difference in toxicities and clinical outcome of chemoradiation in urban and rural cervical cancer patient. This was a prospective study. In a double-arm prospective study, cervical cancer patients were treated with chemoradiation followed by brachytherapy. Patients were monitored weekly for hematological, gastrointestinal toxicities, and electrolyte imbalance. Acute toxicities and long-term outcome were compared between the two groups. Kaplan-Meier survival curves for analysis of disease free and overall survival and Pearson's Chi-square test and Fisher's exact tests for analysis of toxicities were used. Fifty-seven patients from urban and 114 from rural region were studied. There were no difference between the two groups as far as the patient characteristics, overall treatment time (OTT), hematological, electrolyte imbalance, local control, and disease-free survival between the two groups. Associated comorbidities were significantly higher (53% vs. 17%) with P < 0.0001 in urban population. Grade II and III enteritis were significantly higher 15.78% versus 21.05% (P = 0.00001) and 12.28% versus 11.40% (P = 0.03) in urban patients, respectively. Tolerance to chemoradiation, disease-free survival, and overall survival are similar in both urban and rural patients of cervical cancer, with more enteritis in urban group. However, this did not increase OTT.

OC-0830 Systemic recurrence after primary chemoradiation in cervical cancer patients – an EMBRACE analysis

OC-0830 Systemic recurrence after primary chemoradiation in cervical cancer patients – an EMBRACE analysis

Improvement in Patient-Reported Distress after Chemo-Radiation in Cervical Cancer Patients

Curative treatment of cervical cancer with definitive chemo-radiotherapy (CRT) can be associated with significant morbidity impacting quality of life and causing distress. Our objective was to evaluate the clinical utility of prospectively collected patient-reported distress over time in cervical cancer patients treated with definitive CRT using the Edmonton Symptom Assessment System (ESAS) questionnaire. Between 2011 and 2016, consenting cervical cancer patients treated with definitive CRT who completed ≥ 2 questionnaires at routine clinical visits, including baseline, were included. The ESAS is a validated 10-item patient-reported symptom screening tool. Items are scored 0-10 and summed to a total score with higher scores indicating higher distress. Mean total scores were calculated at all time points and compared to baseline using a paired t-test. For each patient, a slope was created using linear regression. A one-sample t-test was performed on the slopes to determine whether the degree of change differed from zero. The minimal clinically important difference (MCID) for total ESAS score was defined as a change of 3-points for improvement and 4-points for deterioration. A mixed model was used to evaluate the longitudinal change in the MCID from baseline. Of the 98 patients initially identified, 68 met inclusion criteria. Median (range) follow-up was 16 mos (2-57) and compliance at 12 mos was 57% (39/68). The median (range) age at diagnosis was 46 years (30-77) and 32%, 53%, 15% were FIGO stages IB, IIA-B, and IIIA-B respectively. All patients received external beam radiation with concurrent cisplatin followed by MR-guided PDR (47%) or HDR (53%) brachytherapy with 59% intracavitary and 41% combined intracavitary/interstitial techniques. There was no difference in total score at baseline compared to end of treatment (p=0.50), but reductions in distress were observed at 6 weeks, 3 mos and 6 mos after treatment compared to baseline (p=0.03, p=0.008 and p=<0.001, respectively). There was a significant improvement in distress over time for each patient reflected in the change in slope (mean slope: -0.79; 95% confidence interval: -1.31, -0.27; p=0.004). There was also a significant improvement in the MCID for total score from baseline over time (p=0.04). Cervical cancer patients experience significant distress at diagnosis and during definitive CRT that significantly improves over time after treatment to an extent that is expected to be clinically meaningful for patients as defined by the MCID. Prospective collection of cervix cancer specific patient-reported outcomes should be incorporated into routine clinical practice to better inform areas of need and survivorship planning.

Age-corrected hearing loss after chemoradiation in cervical cancer patients.

This study aimed to evaluate subjective and objective hearing loss in cervical cancer patients after chemoradiation with cisplatin (mono). A total of 51 cervical cancer patients with indication for chemoradiation were included. Pure tone and impedance audiometry were performed before and after chemoradiation. Hearing loss was scaled according to ASHA criteria. Subjective hearing was assessed with the Oldenburger Sentence Test. To consider age-dependent changes, hearing loss was corrected for age and the time interval between measurements. Median age at diagnosis was 46years, 46% were active/former smokers (n = 24), 28 (54%) patients were never-smokers. Median total weekly cisplatin dose was 70 ± 14.2 mg. Cumulative doses of cisplatin during chemoradiation ranged between 115.2 and 400 mg cisplatin (mean 336.1 mg, median 342 ± 52.7 mg). The median interval between last chemotherapy and second audiometry was 320 ± 538days (35-2262days). Changes in hearing threshold ≥20 dB were experienced by 32/52patients (62%) following chemoradiation, 55% of them for frequencies ≥6000 Hz. No statistically significant hearing loss remained after chemoradiation upon correction for age and time interval. Patients >40years had ahigher risk of hearing loss than younger patients. Objective data on hearing function did not correlate with subjective hearing loss and did not impair daily activity in any patient. Chemoradiation with cumulative cisplatin doses up to 400 mg did not lead to significant impairment of objective or subjective hearing. For cervical cancer patients undergoing chemoradiation, standard audiometry is not indicated.

EP-2221: Overweight is associated with pelvic nodal failure after chemoradiation in cervical cancer patients

EP-2221: Overweight is associated with pelvic nodal failure after chemoradiation in cervical cancer patients

Does fall in serum glutathione predict the long-term outcome to concurrent chemoradiation for cervical cancer patients?

Wide variations are seen in clinical practice with respect to response to concurrent chemo radiation among cervical cancer patients. Fall in serum glutathione (GSH) level directly correlates with early response to treatment. Whether this early response translates to a better long term outcome is the subject of this prospective study. Thirty eight women with cervical cancer were treated with concurrent chemo radiation followed by brachytherapy. Serum GSH was measured before and after two fractions of radiation and first chemotherapy. Patients were followed for a median follow up of four years. Fall in GSH was correlated with response at six weeks and disease status at four years. Median fall in serum GSH was 171.16 µg per ml. Fall in GSH was 170.42, 103.54 and 37.25 µg per ml (P value of <0.0001, 0.05 and 0.18) in patients showing complete response, partial response and no response respectively. Among 26 patients who had no disease at six weeks, 22 women remained disease free at four years (P < 0.0001), two recurred (P < 0.05) and two died of other causes respectively. Non bulky tumours and patients more than 50 years of age showed a fall of 190.69, 265.17 µg per ml respectively. Greater fall in serum GSH predicts better early response as well as long term disease control.

Feasibility of Concurrent Chemoradiation in Cervical Cancer Patients From Rural Background

BackgroundConcurrent chemoradiation causes toxicities such as enteritis, hematologic toxicities which may lead to treatment interruptions, and therefore inferior outcomes. Adequate supportive care is very important to complete the scheduled protocol. Most of our patients are from rural background with a heterogeneous social background (nutrition and social support). There is paucity of literature to evaluate the tolerance of this intense treatment in these groups of patients, and hence, this study was undertaken. MethodsIn this observational study, 30 rural women having carcinoma cervix treated with concurrent chemoradiation between January and July 2013 were reviewed retrospectively. They were assessed weekly for dyselectrolytemia, enteritis, and hematologic toxicity using Radiation Therapy Oncology Group Acute Radiation Morbidity Scoring Criteria. Treatment gaps along with reasons were recorded and correlated. ResultsMedian age of patients was 54 years. Of the patients, 43.3% were International Federation of Gynecology and Obstetrics stage II and 46.7% stage III. Grade 3 enteritis was seen in 7 of 30 patients (23.3%). None (0%) had grade 3 or higher hematologic toxicity. Dyselectrolytemia–hyponatremia (46.66%), hypokalemia (26.66%), hypocalcemia (6.66%), and hypomagnesemia (10%) were noted. Two of thirty patients (6.66%) received the planned 5 cycles, cisplatin 40 mg/m2 weekly. There were treatment interruptions in radiation in 6 (20%) and treatment delays in chemotherapy in 10 (33.33%) patients. ConclusionConcurrent chemoradiation for patients from rural areas is associated with higher acute toxicities. Regular monitoring for enteritis and dyselectrolytemias and timely intervention can help improve compliance and decrease treatment interruptions and thereby achieve the optimum treatment outcome.

Extended field chemoradiation for cervical cancer patients with histologically proven para-aortic lymph node metastases after laparaoscopic lymphadenectomy.

The purpose of this work was to evaluate the use of extended-field chemoradiation (EFRT) with concomitant chemotherapy in patients with histologically confirmed para-aortic metastases after laparoscopic para-aortic and pelvic lymphadenectomy (LAE) with regard to oncologic results and treatment-related toxicity. A total of 44women with squamous cell carcinoma (82 %) and adenocarcinoma (18 %) of the cervix in FIGO stagesIIA (n = 3), IIB (n = 29); IIIB (n = 9), and IVA (n = 3) and histologically proven para-aortic metastases underwent EFRT and chemotherapy. Laparoscopic LAE was performed in 40patients. Patients underwent chemoradiation with conventional fractionation of 1.8-50.4Gy to the para-aortic and pelvic region. In addition, MRI-guided brachytherapy was performed to the cervix with 5-6single doses of 5Gy for a total dose of 25-30Gy. The mean number of harvested lymph nodes was 17 in the pelvic as well as para-aortic regions, respectively. Laparoscopic intervention did not delay chemoradiation. Follow-up was 6-76months (mean 25.1months). There was no grade4 or 5 acute radiation toxicity. In all, 8, 4, and 11 % grade 1, 2, and 3 gastrointestinal late toxicities and 7, 11, and 19 % grade 1, 2 and 3 genitourinary late toxicities were recorded. Despite the excellent locoregional (pelvic) control rates of 89.1 and 82.8 % after 2 and 5years, respectively, the overall survival rates were 68.4 and 54.1 % after 2 and 5years, respectively. Of the 44patients, 43 remained tumor free in the para-aortic region. In patients with proven para-aortic disease, excellent pelvic and para-aortic control could be achieved by laparoscopic LAE followed by EFRT. More than half of the patients were long-term survivors. The high risk of distant metastases should be addressed by further improving systemic treatment.

219 Phase I trial evaluating the antiviral agent Cidofovir in combination with chemoradiation in cervical cancer patients: A novel approach to treat HPV related malignancies?

219 Phase I trial evaluating the antiviral agent Cidofovir in combination with chemoradiation in cervical cancer patients: A novel approach to treat HPV related malignancies?

Single nucleotide polymorphisms analysis of BRAC and ERCC1 as predictor of recurrence after chemoradiation for cervical cancer patients.

e13540 Background: A number of patients with locally advanced cervical cancer will recur despite presenting initial response to chemoradiation. Single-nucleotide polymorphisms (SNP) of DNA repair genes have been found to be predictors of efficacy of chemotherapy and radiotherapy. Methods: We evaluated the presence of SNP in ERCC1, BRAC 1 and 2 genes. We analysed paraffin-embedded biopsies from patients who had relapsed after receiving treatment with chemoradiation, for SNP of the mentioned genes. The status of the alleles wild type (wt) or at least 1 SNP was compared with time to progression (TTP) and toxicity. Results: 90 patients who experience recurrence of their cervical cancer were included in the analysis. Of those, we only could obtain evaluable tumour from 43 patients. Median age: 52.5 yrs (31-81). Histology: 32 squamous cell, 8 adenocarcinoma, 3 adenosquamous. One SNP in BRAC1 (rs12516) was found to be significantly associated with better TTP for the mutant variant compared to the wild-type (124 m. vs. 14 m.). Furthermore, all six patients who presented with severe (grade 3-4) toxicity had this wild-type SNP (rs12516) in BRAC1 gene. Conclusions: We have identified a SNP which confers better outcome in patients with cervical cancer. Further analysis need to be done to determine its relation to radiation-induced toxicity in this group of patients.

Helical Tomotherapy Versus Conventional Intensity-Modulated Radiation Therapy for Primary Chemoradiation in Cervical Cancer Patients: An Intraindividual Comparison

To compare intensity-modulated radiotherapy (IMRT) delivered by helical tomotherapy (HT) with conventional IMRT for primary chemoradiation in cervical cancer patients. Twenty cervical cancer patients undergoing primary chemoradiation received radiation with HT; 10 patients underwent pelvic irradiation (PEL) and 10 extended-field irradiation (EXT). For treatment planning, the simultaneously integrated boost (SIB) concept was applied. Tumor, pelvic, with or without para-aortic lymph nodes were defined as planning target volume A (PTV-A) with a prescribed dose of 1.8/50.4 Gy (28 fractions). The SIB dose for the parametrium (PTV-B), was 2.12/59.36 Gy. The lower target constraints were 95% of the prescribed dose in 95% of the target volume, and the upper dose constraint was 107%. The irradiated small-bowel volumes were kept as low as possible. For every HT plan, a conventional IMRT plan was calculated and compared with regard to dose-volume histogram, conformity index and conformity number, and homogeneity index. Both techniques allowed excellent target volume coverage and sufficient SB sparing. Conformity index and conformity number results for both PTV-A and PTV-B, homogeneity index for PTV-B, and SB sparing for V45, V50, Dmax, and D1% were significantly better with HT. SB sparing was significantly better for conventional IMRT at low doses (V10). Both HT and conventional IMRT provide optimal treatment of cervical cancer patients. The HT technique was significantly favored with regard to target conformity, homogeneity, and SB sparing. Randomized trials are needed to assess the oncological outcome, toxicity, and clinical relevance of these differences.

Intensity-Modulated Radiotherapy in Patients with Cervical Cancer. An intra-individual Comparison of Prone and Supine Positioning

BackgroundChemoradiation for cervical cancer patients is associated with considerable gastrointestinal toxicity. Intensity-modulated radiotherapy (IMRT) has demonstrated superiority in terms of target coverage and normal tissue sparing in comparison to conventional 3D planning in gynaecological malignancies. Whether IMRT in prone (PP) or supine position (SP) might be beneficial for cervical cancer patients remains partially unanswered.Methods10 patients on FIGO stage IB-III cervical cancer, 6 patients for definitive and 4 patients for adjuvant external beam pelvic RT, were planned in PP and SP using a 7-field IMRT technique. IMRT plans for PP and SP (mean dose, Dmean 50.4 Gy) were optimized in terms of PTV coverage (1st priority) and small bowel sparing (2nd priority). A comparison of DVH parameters for PTV, small bowel, bladder, and rectum was performed.ResultsThe comparison showed a similar PTV coverage of 95% of the prescribed dose and for target conformity in IMRT plans (PP, SP). PTV, rectum and bladder volumes were comparable for PP and SP. Significantly larger volumes of small bowel were found in PP (436 cc, + 35%, p = 0.01). PP decreased the volume of small bowel at 20-50.4 Gy (p < 0.05) and increased the rectum volumes covered by doses from 10-40 Gy (p < 0.01), the V50.4 was < 5% in both treatment positions. Bladder sparing was significant better at 50.4 Gy (p = 0.03) for PP.ConclusionIn this dosimetric study, we demonstrated that pelvic IMRT in prone position for patients with cervical cancer seems to be beneficial in reducing small bowel volume at doses ≥20 Gy while providing similar target coverage and target conformity. The use of frequent image guidance with KV (kilovolt) or MV (megavolt) computertomography can reduce set-up deviations, and treatment in prone position can be done with a higher set-up accuracy. Clinical outcome studies are needed to affirm lower toxicity.