Completion Of External Beam Radiotherapy Research Articles

Exploratory study of using Magnetic resonance Prognostic Imaging markers for Radiotherapy In Cervix cancer (EMPIRIC): a prospective cohort study protocol

IntroductionRadical chemoradiotherapy represents the gold standard for locally advanced cervical cancer. However, despite significant progress in improving local tumour control, distant relapse continues to impact overall survival. The development of...

Compare Two Different Fractionated Regimes of HDR Intracavitary Brachytherapy after Concomitant Chemoradiation in Carcinoma Cervix: A Prospective Study

Background: Cervical cancer is the common cancer cause of death among women in developing countries. High Dose Rate (HDR) intracavitary brachytherapy that is given with or sequential after EBRT, is an integral component in the treatment of carcinoma of the cervix. In recent years, High Dose Rate (HDR) brachytherapy in combination with External Beam Radiotherapy (EBRT) has been popular in the management of carcinoma of the cervix. Objectives: To evaluate treatment response post 3 and 6 months after treatment completion and treatment-related toxicities during treatment in weekly v/s biweekly HDR intracavitary brachytherapy after concomitant chemoradiation in squamous cell carcinoma cervix patients. Methods: A total of 60 cervical cancer patients fulfilling the inclusion criteria were selected. Patients were randomly assigned to the weekly and Biweekly HDR ICBT using the chit-box method with replacement. Arm A (Study arm): 30 patients with concurrent EBRT (50 Gy/25 fractions with 2 Gy per fraction) with weekly cisplatin (35 mg/m2) followed by HDR-ICBT 5 Gy * 5 fractions biweekly after completion of EBRT. Arm B (Control arm): 30 patients with concurrent EBRT (50 Gy/25 fractions with 2 Gy per fraction) with weekly cisplatin (35 mg/ m2) followed by HDR - ICBT 7.5 Gy * 3 fractions weekly after completion of EBRT. Results: Patients were assessed at 3 and 6 months to determine the local disease response and the incidence of any toxicities assessed during the treatment. All responses were graded as either CR (complete response), PR (partial response), SD (stable disease), or PD (progressive disease). 30 patients were assessed for therapy response using the WHO criteria. At 3 months arm A showed 86% CR and arm B showed 90% CR. 2 patients in arm A and 1 patient in arm B had PR. In both arms 2 patients had progressive disease. At 6 months 1 patient in both arms who had progressive disease converted into partial response after taking post RT chemotherapy. Conclusions: To sum up, brachytherapy is a vital aspect of the process of treating cervical cancer. Several centers have experimented with various doses and fractionation regimes. Patients in the current trial reported no safety concerns or intolerability issues across any treatment protocol. Arm A had treatment completion before arm B with comparable disease response and toxicities. Therefore, the choice of treatment plan depends on the individual patient’s circumstances and the institution’s demands. nonetheless, longer follow-ups and a bigger patient sample are needed for a solid evaluation of disease response and toxicity.

External Beam Radiotherapy Interdigitated with High Dose Rate(HDR) Intracavitary Brachytherapy versus External Beam Radiotherapy followed by Sequential HDR Intracavitary Brachytherapy for Locally Advanced Carcinoma Cervix-Randomized Control Study.

In cervical cancer treatment, overall treatment time (OTT) is an important prognostic factor. This study compares the clinical outcomes when High-Dose-Rate Intracavitary-Brachytherapy(HDR-ICRT) is interdigitated with external beam radiotherapy(EBRT) versus sequential HDR-ICRT after EBRT in the treatment of locally advanced carcinoma cervix. Histologically confirmed carcinoma cervix patients [FIGO Stage IIB-IVA (except IIIC-2)] were included and randomized into two groups. The study group received EBRT 50Gy in 25 fractions with interdigitated HDR-ICRT 7Gy per fraction weekly for three fractions starting after completion of 3 weeks of EBRT or as soon as cervical os became negotiable thereafter. Patients in the control group received EBRT 50Gy in 25 fractions with sequential HDR-ICRT 7Gy per fraction weekly for three fractions starting one week after completion of EBRT. All patients were regularly followed up during and after radiotherapy for local toxicity and disease control. This study enrolled 102 patients; 51 in each arm. Median OTT in study and control arm were 46 and 60 days, respectively. Median follow-up duration was 24 months (two years). Loco-regional control after two years of follow-up was 84.31 % and 72.54% of patients in study arm control arm respectively (p-value 0.148). Two (3.92%) patients from study arm and eight (15.68%) from control arm had residual disease. Two patients in study arm and one from control arm had local recurrence. Two patients from study arm three patients from control arm developed distant metastases. RTOG mucosal grade III acute mucosal toxicity in either arm. Cervical-os negotiability was limiting factor for interdigitated HDR-ICRT. Interdigitated HDR-ICRT with EBRT may give local control with manageable toxicities as compared to sequential HDR-ICRT, with the advantage of significant reduction in OTT.<br />.

Initial Clinical Outcomes of a Phase II Trial of Focal Salvage LDR Brachytherapy for Local Recurrence of Prostate Cancer after External Beam Radiation Therapy.

To evaluate the clinical outcomes of focal salvage low dose rate brachytherapy (FSB) for biopsy proven local recurrence of prostate cancer after definitive external beam radiation therapy (EBRT). Patients with a Phoenix definition PSA recurrence (nadir + 2.0ng/dL) after definitive EBRT for localized prostate cancer and a negative metastatic work up were enrolled in a Phase II clinical trial. Patients first underwent MR-guided transperineal mapping biopsy of the prostate using a template grid. Patients with a pathologically confirmed recurrence underwent FSB using iodine-125 seeds to a prescription dose of 145 Gy. The brachytherapy planning target volume (PTV) was defined by the positions of the pathologically negative core biopsies adjacent to the positive core biopsies as recorded on the template grid during the biopsy procedure. An intraoperative treatment plan was then developed to cover the PTV with the 145 Gy isodose line. Follow up included assessment of genitourinary (GU) and gastrointestinal (GI) toxicities using Common Terminology Criteria for Adverse Events version 4.03 (CTCAEv4.03), patient reported outcomes using the International Prostate Symptom Score (IPSS) and Expanded Prostate Cancer Index-26 (EPIC-26) forms, and serial PSA blood draws. Ten patients underwent FSB. The median prior EBRT dose was 7805 cGy (interquartile range IQR 7560-7920) and the median time from completion of EBRT to FSB was 81 months (IQR 68-134). The median PSA prior to FSB was 3.2 ng/dL (IQR 2.3 - 4.5). The median follow up after FSB was 32 months (IQR 18-57). Eight patients were free of Phoenix definition PSA failure at last follow up. Of the two patients who experienced a PSA failure, one developed distant metastases 5 months after FSB and the other a biopsy proven seminal vesicle recurrence 3 years after FSB. The median change in post FSB IPSS score compared to the pre-FSB IPSS score was an increase of 1.5 (IQR -1.5 to 8) at 3 month follow up and an increase of 3.5 (IQR 0.5 to 5.5) at last follow up (≥1 year). The median change in post FSB EPIC-26 urinary domain score compared to the pre-FSB score was -1 (IQR -26 to +14.5) at 3 month follow up and +2 (IQR -12.5 to +14.5) at last follow up (≥1 year). The median change in post FSB EPIC-26 bowel domain score compared to the pre-FSB score was -2 (IQR -9.5 to 0.0) at 3 month follow up and 0 (IQR -6.0 to +3.0) at last follow up (≥1 year). No patients experienced post FSB Grade 3 or higher GU or GI toxicities. High dose FSB for a local recurrence of prostate cancer after EBRT can be delivered with good biochemical control and a favorable toxicity profile. Further clinical trial enrollment and longer follow up will be needed to better assess long term outcomes.

Effect of External Beam Radiation Therapy (EBRT) and Brachytherapy (BT) on Circulating MDSC Populations in Patients Treated Definitively for Cervical Cancer

The immunosuppressive function of myeloid derived suppressor cells (MDSCs) has been implicated in the regulation of immune responses against cancer. MDSCs have been associated with progression and poor response to therapy in various types of cancer, including cervical cancer. Radiation treatment (RT) alters immune cell populations within the tumor and is thought to augment antitumor responses. However, whether RT also recruits immunosuppressive MDSC populations is not well understood. Here, we investigate how circulating MDSC populations change in response to RT and if changes in MDSC frequency or subsets is predictive of RT responses in cervical cancer patients. Newly diagnosed, treatment-naïve pts with locally advanced carcinoma of the cervix will be enrolled from July 2022 to July 2023. EBRT to the pelvis was delivered at a dose of 45 Gy in 25 fractions with a simultaneous integrated boost of 52-55 Gy to involved regional lymph nodes and parametria and concurrent weekly cisplatin. Gross tumor was boosted via interstitial or tandem ring BT (22.5-27.5 Gy) after completion of EBRT. Serial blood samples were collected prior to initiating therapy (T0), post-EBRT and pre-BT (T1), and one-month post-BT (T2). Treatment response was determined based on pre-treatment MRI compared to MRI post-EBRT. Peripheral blood mononuclear cells (PBMCs) were isolated from whole blood using density gradient centrifugation and stained for analysis via flow cytometry. MDSC populations were identified by Live/Dead-CD11b+CD33+HLA-DR- staining. MDSC subsets were further subdivided into granulocytic (G-, CD15+CD14-), monocytic (M-, CD15-CD14+), or early-MDSCs (e-, CD15-CD14-). Blood samples were collected at indicated time points for four patients (FIGO stage IIA-IIB). Three had partial responses to chemoradiotherapy (CRT), while one had a complete response. All three patients with partial response had an increase in total frequency of circulating MDSCs in response to EBRT/BT (mean %fx MDSC 16.6 at T0 to 35.9 at T2), and an increase in total MDSCs in two of these patients occurred with EBRT alone. Interestingly, the patient that had a complete response had fewer MDSCs at T2 relative to T0 (35.8% at T0 to 27% at T2). Proportion of MDSC subsets varied considerably among the patients, and all had altered distribution of subsets in response to RT. G-MDSCs expanded the most to RT while M-MDSCs and e-MDSCs were less affected (mean fold change from T0 to T2 G-MDSC 4.75, M-MDSC 1.27, e-MDSC 0.942). In this cohort of patients, an increase in MDSC frequency occurred after RT and altered subset distribution. Only the patient with a complete response had fewer total MDSCs following completion of CRT, suggesting further studies are needed to determine if circulating MDSCs could be a biomarker for treatment response to RT in cervical cancer.

Multiple Sessions vs. Single Session Image-Based Intracavitary Brachytherapy for Locally Advanced Cervical Cancer: A Randomized Control Trial

The objectives of this study are: 1) To compare the acute toxicity caused in the treatment of locally advanced cervical cancer (LACC) treated with weekly multiple applications vs. a single application for image-guided intracavitary High Dose Rate (HDR) brachytherapy (BT) after External Beam Radiation Therapy (EBRT) 2) To compare the loco-regional control of cancer at six months in the two arms MATERIALS/METHODS: In a prospective study, 40 patients with biopsy-proven LACC with FIGO-2018 stage IIB-IIIC1 disease, underwent EBRT to the pelvis at a dose of 50.4 Gy/ 28 fractions over 5.5 weeks with weekly concurrent cisplatin. After completion of EBRT, they were randomized into two arms with 20 patients each. In the Control arm (Arm-A), BT sessions were given with weekly 3 applications whereas, in the experimental arm (Arm-B), all the sessions were given with a single application at 6-12 hours intervals with aim of the high-risk clinical target volume receiving >80 Gy EQD2 and 2 cm3 of the bladder and rectum/sigmoid receiving <85 Gy and <75 Gy, respectively. The OAR contouring was done on CT RESULTS: All 40 patients were treated as per protocol. The mean duration of treatment including EBRT and BT was 73.15 days [95% CI 68.63-77.66] in Arm A and 55.85 days [95% CI 52.11-59.58] in Arm B which was significant. After 6 months, 37 patients came for follow-up, all 19 patients in Arm A had Grade 1 or Grade 2 rectal toxicity. In Arm B as well all 18 patients had Grade 1 or Grade 2 rectal toxicity. Bladder toxicity was Grade 1 or Grade 2 in 18 patients and Grade 3 severity in 1 patient among Arm A. Among 18 patients of Arm B, bladder toxicity of Grade 1 or Grade 2 was seen in 16 patients, and 2 patients had grade 3 toxicity. 2 patients in Arm A and 3 in Arm B complained of Grade 1 urinary incontinence. Moreover, Abdominal pain at 6 months was of Grade 1 in around 6 patients in Arm A but 14 patients had abdominal pain in Arm B which was of Grade 1 in 8, 4 had grade 2 and 2 patients had grade 3 severity abdominal pain. In the monthly analysis of acute toxicity, none of the patients showed Grade 3 or 4 toxicity at the 1st, 2nd, or 3rd month of completion of treatment. When comparing local control in both arms at 6 months, 2 patients had treatment failure in the Experimental Arm compared to only 1 patient in the Control Arm CONCLUSION: Single Application Multiple Fraction Intracavitary Brachytherapy post concurrent CTRT is a safe option for the treatment of locally advanced cervical cancer. When compared to the weekly application arm, single-application ICRT showed a comparable acute toxicity profile and comparable local control rates as well. Some patients in Single Application Arm showed abdominal pain which needs to be investigated with further trials. The overall treatment time in the single application arm is significantly lower than the standard weekly application arm.

Prophylactic Para-Aortic Extended Field Irradiation with Concurrent Chemotherapy for FIGO Stage IIIC1 Cervical Cancer Using Intensity Modulated Radiotherapy Technique: Acute Toxicity and Dosimetric Assessment

To evaluate the efficacy of P - PART with concurrent chemotherapy in LACC with the use of intensity modulated radiotherapy technique (IMRT). Our Primary endpoint was to assess acute toxicities and secondary endpoint was to assess loco-regional control (LRC), disease free-survival (DFS), para-aortic recurrence free survival (PA-RFS). A total of 30 patients of squamous cell carcinoma of cervix with stage IIIC1 (FIGO-2018) were recruited in this prospective, single arm interventional phase II study between January 2021 to September 2022. 18FDG-PET CT was performed and those with positive PALN were excluded. IMRT was used to deliver a dose of 50 Gy in 25 fractions to whole pelvis and PALN chain below renal hilum till aortic bifurcation received 45 Gy in 25 fractions. Concurrent cisplatin was administered weekly at 40 mg/m2 during radiation. On completion of external beam radiotherapy, high dose rate intracavitary brachytherapy was given at 7 Gy per fraction in 3 fractions prescribed to HR-CTV. Acute toxicities were assessed using CTCAE version 5.0. Median age was 50 years (37-66 years). All patients had completed treatment as per protocol. All patients had positive pelvic nodes with the maximum nodal short axis dimension of 14 mm (10-18 mm). All patients had positive internal iliac group of LNs, only 2(6.6%) patients had positive common iliac group of Ln. Median number of concurrent cisplatin cycles given were 5 (3-5 cycle). Median overall treatment time was 56 days (52-63 days) and median follow up was 15 months (3-22 month). Median cumulative dose to HR-CTV was 84.3Gy (Range:79.2-86.9Gy). Cumulative median EQD2 to 2cc of bladder and rectum were 69.11Gy (Range:59.17 - 80.07 Gy) and 64.6 Gy (Range: 60.1-66.3Gy) respectively. 7(23.3%) patients having grade 3 diarrhea and 2(6.67%) patients had grade 3 anemia while no significant genitourinary or other toxicities were noted. Patient characteristics, dosimetric data are described in Table-1. All patients underwent clinical and radiological assessment at the time of last follow up with one (3.33%) patient experiencing local failure at 9 months of follow up, hence crude LRC rate is 96.6%, DFS is 13.5 months (5-22 months) and PA-RFS is 16 months (8-23 months) till last date of follow up. Prophylactic EFRT with concurrent chemotherapy using IMRT technique yielded excellent short term clinical outcomes with acceptable toxicity profiles. Longer follow up will elucidate late toxicity and long-term clinical outcomes.

Pre-Brachytherapy Diffusion-Weighted Magnetic Resonance Imaging (DW-MRI) Response as Predictor of Local Control in the Definitive Treatment of Cervical Cancer

Chemoradiation consisting of external beam radiotherapy (EBRT) followed by brachytherapy (BT) is the standard of care for Stage IB2-IVA cervical cancer (CC). Multi-parametric MRI (mpMRI) is a valuable tool for initial staging, treatment planning and response assessment. In this study, we aim to explore the potential of mpMRI, in particular DW-MRI, to predict overall tumor control following chemoradiation in CC. We identified 78 consecutive patients treated with chemoradiation for FIGO IB2-IVA CC between 2012-2020, who had an MRI at baseline (MRb) and post-EBRT prior to brachytherapy boost (MRpb) that included DW-MRI (b-value = 0 and 800 s/mm2). Median age was 53 years, most patients had squamous cell carcinoma (76.9%) and advanced-stage disease (56.4% stage IIIA-IVA). Median time from completion of EBRT to MRpb was 3 days. Regions of interest (ROI) in primary tumor were delineated on DW image (b = 0 s/mm2) using ITK-SNAP software. DW-MRI data were fitted to a monoexponential model to calculate apparent diffusion coefficient (ADC) values using in-house software platform (MRI-QAMPER). MRpb mean ADC values (n = 78) and relative changes (%) in mean ADC values between MRb and MRpb (n = 64) were correlated with outcomes, including local failure (LF), regional or distant failure (RDF), and failure at any site (FAS), with death without failure as a competing risk. Median follow-up time was 45 months (95% CI 38, 53). At first post treatment assessment, 72 patients (92.3%) had a complete response (CR) in the cervix and 68 patients (87.2%) had CR in all disease sites. Of patients who had CR in the cervix (n = 72), only 1 patient had local recurrence. Of patients who had CR in all disease sites, 10 later recurred (1 LF only, 1 LF&RDF, 8 RDF only). Overall, 7 patients (9%) had LF, and 19 patients (24.4%) had FAS. A higher mean ADC value in MRpb was associated with LF (HR 4.3, 95% CI 1.32, 14.6; P = 0.016), but not with RDF (P = 0.4) or FAS (P = 0.5). A higher relative change in the mean ADC value between MRb and MRpb was associated with a lower risk of LF (HR 0.94, 95% CI 0.90, 0.98; P = 0.002), but not with RDF (P = 0.8) or FAS (P = 0.4). Treatment response as measured on prebrachytherapy DW-MRI is a significant predictor of local control in patients undergoing chemoradiation for stage IB2-IVA CC. ADC values, a quantitative imaging biomarker on MRpb may be instrumental in dose intensification/de-escalation efforts in CC.

Toxicity and Dosimetric Analysis of Reirradiation of Head and Neck Cancers with High Dose Rate Brachytherapy

Reirradiation (reRT) of recurrent or second primary head and neck cancers (HNC) after prior curative-intent external beam radiotherapy (EBRT) has historically achieved local control (LC) rates of 40-50% and been associated with high grade toxicity rates estimated at 25-50%. This study evaluated the hypothesis that patients with small reRT target volumes could be selected for high dose rate brachytherapy (HDR-BT) reRT and achieve similar LC without excess toxicity. Included were all patients with HNC squamous cell carcinoma treated with HDR-BT after having previously received curative-intent EBRT for primary HNC from 2000-2021. Patients were selected by a multidisciplinary tumor board to be appropriate candidates for HDR-BT reRT without EBRT generally for definitive or adjuvant treatment of small primary tumors without neck nodal metastases. Univariate analysis was performed using the logistic regression model. Survival outcomes were estimated with the Kaplan Meier method. Twenty-three patients were evaluated. Median follow up time was 19mo. Median age at time of HDR-BT was 64 years. Thirteen patients (57%) were treated for recurrent HNC, of which 7 were in the oral cavity (OC) and 6 were the oropharynx (OPX). Ten patients (43%) were treated for a second primary HNC, of which 5 were in the OC and 5 were in the OPX. Median time from completion of EBRT to HDR-BT was 41 (IQR 14-73) mo. Within their reRT course, 11 patients (48%) were treated with HDR-BT after resection, 9 patients (39%) received concurrent hyperthermia, and 7 patients (30%) received chemotherapy. HDR-BT regimens included 600cGy x5 (N = 11), 600cGy x6 (N = 6), 450cGy x8 (N = 1), 1500cGy x1 (N = 1),1000cGy x1 (N = 1), 500cGy x8 (N = 1), and 700cGy x5 (N = 1). One patient who was treated with two implants received 450cGy x 3 followed by 475cGy x5. A median of 5 brachytherapy catheters were used. Actuarial 2-year LC and overall survival rate was 68% and 62%, respectively. Of the 17 HDR-BT reRT plans available for review, median (IQR) target volume was 15.8 (10.6-34.9) cc. Median (IQR) target V100% was 90.6 (89.4-90.0)%, V150% was 50.5 (49.7-54.4)%, and V200% was 25.4 (23.8-29.0)%. Median (IQR) target D90% was 30.1 (29.8-35.5) Gy, and median D1cc was 116.4 (100.5-171.4) Gy. The mandible dose [median (IQR)] was D2cc:15.1(9.48-18.9) Gy; D1cc:16.9(11.1-21.3) Gy; and D1%:18.8(13.4-22.7) Gy. Nine of the 23 patients (39%) experienced ≥G3 toxicity including fistula, soft tissue necrosis, osteoradionecrosis, ulcer, hemorrhage, and dysphagia requiring a chronic feeding tube. Target D90% was associated with ≥G3 toxicity (p = 0.045). For D90% greater than the median of 30Gy, 45% ≥G3 toxicity was observed. This study suggests that HDR-BT for reRT of small recurrent or second primary HNC can provide similar LC without excess high-grade toxicities as compared to historical outcomes with EBRT reRT. Delivery of equivalent doses higher than 30Gy in 5 fractions should be approached with caution.

Conditional Risks of Biochemical Failure and Prostate Cancer–Specific Death in Patients Undergoing External Beam Radiotherapy

As patients achieve years of survival after treatment for prostate cancer, the risk of biochemical failure (BF) or prostate cancer-specific death (PCSD) may evolve over time, with clinical relevance to both patients and clinicians. To determine conditional BF-free survival, PSCD, and overall survival estimates for patients with low- or intermediate-risk prostate cancer enrolled in the Radiation Therapy Oncology Group (RTOG) 0126 and RTOG 0415 clinical trials. A secondary objective was to determine whether prognostic factors at diagnosis remain relevant at later points in follow-up. A pooled secondary analysis of patients treated with external-beam radiotherapy alone and enrolled in the prospective randomized clinical trials RTOG 0126 and RTOG 0415 was performed. Patients included for analysis were enrolled between March 2002 and December 2009 with a median follow-up of 6.9 years. Overall survival was calculated using the Kaplan-Meier method at various survivorship time points. Cumulative incidence was used to calculate BF rates using the Phoenix definition, as well as PCSD. Risk factors such as Gleason score, tumor (T) stage, prostate-specific antigen level, and the equivalent dose in 2 Gy fractions of prescribed dose were analyzed at different time points using multivariable Cox proportional hazards modeling. Data were analyzed from November 2021 to February 2023. Conditional risks of BF and PCSD after completion of external-beam radiotherapy. A total of 2591 patients (median [IQR] age, 69 [63-73] years) were included in the study with a mean (range) PSA level of 7.1 (4.7-8.9) ng/mL, 1334 patients (51.5%) with a Gleason score 6 disease, and 1706 patients (65.8%) with T1 disease. Rates of BF from time of treatment were 1.63% (95% CI, 1.20%-2.18%) at 1 year, 7.04% (95% CI, 6.09%-8.08%) at 3 years, 12.54% (95% CI, 11.28%-13.88%) at 5 years, and 22.32% (95% CI, 20.46%-24.24%) at 8 years. For patients surviving 1, 3, and 5 years without BF, the rates of BF in the next 5 years were 14.20% (95% CI, 12.80%-15.66%), 17.19% (95% CI, 15.34%-19.14%), and 18.85% (95% CI, 16.21%-21.64%), respectively. At the initial time point, the rate of PCSD in the next 5 years was 0.66% (95% CI, 0.39%-1.04%). For patients who achieved 1, 3, 5, and 8 years of survivorship, the rates of PCSD in the next 5 years were 1.16% (95% CI, 0.77-1.67) at 1 year, 2.42% (95% CI, 1.74%-3.27%) at 3 years, 2.88% (95% CI, 2.01%-3.99%) at 5 years, and 3.49% (95% CI, 0.98%-8.73%) at 8 years. In this secondary analysis of 2 randomized clinical trials of patients undergoing external beam radiotherapy for prostate cancer, the conditional risks of BF and death from prostate cancer increased with time for patients with low- and intermediate-risk prostate cancer treated with radiotherapy alone. These results could inform optimal trial design and may be helpful information for patients evaluated in follow-up. ClinicalTrials.gov Identifier: NCT00033631; NCT00331773.

Dose at posterior-inferior border of symphysis point: A predictor for vaginal stricture in cervical cancer

PURPOSETo study the effect of various dose-volume parameters on the severity of vaginal stricture (VS) and the correlation of the latter with the posterior-inferior border of symphysis (PIBS) points in locally advanced cervical cancer patients treated with concurrent chemoradiation and brachytherapy. METHODS AND MATERIALSA prospective study was done on 45 histologically proven locally advanced cervical cancer patients between January 2020 and March 2021. All of them were treated with concurrent chemoradiation with 6 MV photon linear accelerator to a dose of 45 Gy/25 fractions in 5 weeks. Twenty-three patients were treated with intracavitary brachytherapy with a dose of 7 Gy/fraction/week for three fractions. Twenty-two patients were treated with interstitial brachytherapy, with 6 Gy/fraction for four fractions, each fraction 6 h apart. Grading of VS was done as per Common Terminology Criteria for Adverse Events version 5. RESULTSThe median followup was 21.5 months. About 37.8% of patients had VS with a median duration of 8.0 months (4.0–12 months). About 22.2% had Grade 1, 6.7% had Grade 2, and 8.9% had Grade 3 toxicity. Doses at PIBS and PIBS−2 points had no correlation with vaginal toxicity, however, the dose at PIBS+2 was significantly associated with VS (p = 0.004). The treated length of the vagina at the time of brachytherapy (p = 0.001), initial tumor volume (p = 0.009), and vaginal involvement after completion of external beam radiotherapy (EBRT) (p = 0.01) were also statistically significant with the development of VS of Grade 2 or more. CONCLUSIONSDose at PIBS + 2, treated length of the vagina with brachytherapy, initial tumor volume, and post-EBRT vaginal involvement are strong predictors for the severity of VS.

GSOR25 Presentation Time: 12:30 PM: Interim Pre-Brachytherapy Magnetic Resonance Imaging (MRpb) Response as Predictor of Local Control in the Definitive Treatment of Cervical Cancer

<h3>Background</h3> External beam radiotherapy (EBRT) followed by brachytherapy is standard of care in the management of cervical cancer. Whether early imaging response can predict longer term outcome is unclear. In this study, we investigated the role of interim pelvic magnetic resonance imaging (MRI), done prior to brachytherapy (BT) in predicting local tumor control. <h3>Methods</h3> We identified 87 consecutive patients who underwent definitive EBRT followed by BT for FIGO IIB-IVA cervical cancer at our institution between 2012 and 2020. The median age was 54 years (range, 23-81 years). Most patients had squamous cell carcinoma (77%), advanced stage disease (57.5% stage IIIA and higher, 51.7% nodal disease) and received concurrent cisplatin (98.8%). All patients had an MRI at baseline (MRb) and prior to brachytherapy boost (MRpb). The median time from completion of EBRT to MRpb was 3 days (IQR: -14d to +1d). EBRT included the regional LNs and primary site (median dose 45Gy, range 45-54Gy). Node positive patients also received a boost (median 5.4Gy, range 5.4-14.4Gy) Fifty-seven patients (65.5%) had intracavitary brachytherapy (median dose 28Gy, range 2-28Gy) and 30 (34.5%) had an interstitial BT (median dose 24Gy, range 20-28Gy). Adjuvant chemotherapy was delivered in 24 cases (27.6%). Patients were followed post-treatment with pelvic exams/cytology every 3 months for years 1-2 and every 6 months thereafter. PET/CT and a pelvic MRI were done 3 months posttreatment and as clinically indicated thereafter. Median follow up time was 35.5 months (range 3.8-114.2 months). Response to EBRT on MRpb was defined as residual disease > 2 cm, residual disease ≤ 2 cm and no measurable disease (complete response, CR). Local failure was defined as recurrent or persistent tumor in the cervix following all treatment and confirmed pathologically. Chi square test was used to compare categorical data. <h3>Results</h3> Overall, 19.5% of patients had a CR, 22.9% had residual disease ≤2cm and 57.5% had residual disease >2cm noted on MRpb. No patients who achieved a CR on MRpb had local recurrence. Of patients with residual disease ≤2 cm on MRpb, 19/20 patients (95%) ultimately achieved CR on subsequent imaging (median time to CR 3.1 months; range, 2.7-8.6 months), none of whom had a local failure. Of patients with residual disease >2 cm on MRpb, 40/50 (80%) ultimately achieved CR on subsequent imaging (median time to CR, 3.6 months; range, 2.1 - 18.6 months). Of the 10 patients with residual disease >2 cm on MRpb who did not achieve a CR, 4 had local failure, 1 had local and distant failure and 5 had regional or distant failure only. Overall, 6/50 (15%) patients with persistent disease >2 cm had local failure, compared with none of the patients who had more profound responses. Local disease response on MRpb did not predict regional or distant failure (p=0.35). <h3>Conclusions</h3> Interim pre-BT MRI seems promising in predicting local tumor control in the definitive management of cervical cancer and could be instrumental in dose intensification/de-escalation efforts. Further investigation of various MRI sequences in predicting response and long-term control is ongoing.

High Dose Rate Brachytherapy Boost After Chemoradiation in Rectal Cancer Patients: A Retrospective Study

Background: The use of neoadjuvant chemoradiation has enhanced local control in rectal cancer patients. Objectives: The aim of this study was to evaluate the feasibility and efficacy of adding a high dose rate (HDR) brachytherapy (BRT) boost in locally advanced rectal cancer. Methods: This retrospective trial was conducted based on the medical records of patients with rectal cancer, who were referred to a tertiary hospital for neoadjuvant treatment. Fifteen patients who were treated with HDR brachytherapy boost after completion of external beam radiotherapy (EBRT) and concurrent chemotherapy were enrolled in the intervention group and 15 patients who were clinically matched (age, sex, stage, and distance of tumor from anal verge) were selected as the control group. EBRT schedule and concurrent chemotherapy regimen were similar in the two groups. The rate of pathological complete response (PCR), downstaging (T staging), and frequency of side effects were compared between the two groups of the study. Results: The mean age of patients was 57.97 ± 9.11 years and 18 patients (60%) were male. The results showed that T 3 and N 1 rectal cancer had the highest frequency among patients. Downstaging was observed in 66.7% and 80% of the control and intervention groups, respectively (P: 0.40). The rate of PCR was not different in the two groups (13.3% in both groups, P &gt; 0.99). There were no significant differences in terms of treatment complications between the two groups, as well. Conclusions: HDR-BRT boost for rectal cancer is feasible and might improve downstaging in rectal cancer, but not PCR.

Concurrent chemoradiotherapy and salvage chemotherapy for advanced cervical cancer with a pedunculated cervical leiomyoma: a case report

Although concurrent chemoradiotherapy (CCRT) is an effective treatment for advanced cervical cancer, its use in advanced cervical cancer with a pedunculated cervical leiomyoma remains challenging. The prognosis of recurrent cervical cancer is poor, with a low possibility of complete response (CR). In this present study, after completion of external beam radiotherapy (EBRT) and chemotherapy (weekly cisplatin), we performed the resection of a pedunculated cervical leiomyoma. No malignant cells were identified in the pathological specimen. After the myoma resection, no cervical tumor was observed on follow-up magnetic resonance imaging (MRI). High-dose-rate intracavitary brachytherapy (HDR-ICBT) was also performed. Local control of the cervical tumor was achieved after 30 months of treatment. After CCRT, rectal hemorrhage was observed but was effectively controlled via local intervention. Twenty-four months after CCRT, the patient was given salvage chemotherapy (paclitaxel plus carboplatin) due to lymph node metastasis observed at the outside range of EBRT. Thirty months after CCRT, computed tomography showed that the metastatic lymph nodes had disappeared, and the patient achieved CR. Thus, for advanced cervical cancer with a pedunculated cervical leiomyoma, CCRT could be completed following myoma resection. In addition, salvage chemotherapy for lymph node metastasis might result in CR. In this present case, a gastrointestinal adverse event was observed after radiotherapy and salvage chemotherapy with paclitaxel plus carboplatin achieved CR.

High-Dose-Rate Intracavitary Brachytherapy Under Conscious Sedation a Viable Practical Alternative to Spinal Anaesthesia in Carcinoma Cervix: A Retrospective Study in a Tertiary Care Centre in Eastern India.

IntroductionIntracavitary brachytherapy (ICBT) is an integral component in the management of locally advanced cervical cancer. Spinal anaesthesia is the preferred mode of pain management during brachytherapy procedures. In high volume, resource constraint settings, it is difficult to provide spinal anaesthesia to all patients. This study attempts dosimetric comparison of high-dose-rate ICBT with spinal anaesthesia to that under conscious sedation to find out whether brachytherapy under conscious sedation is comparable with spinal anaesthesia.MethodsRetrospective data of total of 56 cervical cancer patients who received ICBT after completion of external beam radiotherapy (EBRT) were collected. Among these 56 patients, 28 patients received brachytherapy under spinal anaesthesia (SA group) and the rest under conscious sedation (CS group). Brachytherapy dose was 7 Gray per fraction weekly for three weeks. Thus, 84 brachytherapy plans of each group were analysed with respect to doses received by points A, B, P and Organs at Risk.ResultsThe mean doses received by points A, B and P were comparable in SA and CS groups (p-value >0.05). Similarly, the mean doses received by Organs at Risk (rectum, urinary bladder, and sigmoid colon) were also comparable in both the groups (p-value>0.05).ConclusionICBT under CS is dosimetrically non-inferior to SA, which makes it an alternative option.

Disparities and Health Access in Brachytherapy Boost Administration in Woman With Locally Advanced Cervical Cancer

External beam radiation therapy (EBRT) and brachytherapy boost should be completed in less than eight weeks, as better local tumor control and survival can be expected with relatively shorter treatment courses. We analyzed our institutional experience in total treatment time (TTT) with high dose rate (HDR) brachytherapy boost for patients with locally advanced cervical cancer who received the EBRT portion of their treatment in an outside facility (OF) and treatment outcomes.A single-institution, retrospective IRB-approved study was performed using 101 women with FIGO Stage IB2-IVA cervical cancer treated from 2010 to 2019. Women treated with definitive chemoradiation either in our institution or in an OF followed by HDR brachytherapy boost in our institution were enrolled. TTT was defined as total treatment time in weeks (wk) from initiation of EBRT to the end of HDR brachytherapy. Patients were treated with EBRT to the pelvis only or extended field (EFRT) with or without nodal boosts.101 patients were included in this study. 95% of patients treated at our institution were stage IIB or higher compared to 70% for patients treated at an OF (P < 0.001). TTT was significantly longer for patients who received EBRT at an OF and HDR brachytherapy in our institution compared to patients who received both EBRT and HDR brachytherapy in our institution (9.1 wk vs 7.1 wk, P < 0.05). Increased TTT was associated with inferior mean progression free survival (121 wk vs. 90 wk), although it did not reach significance (P = 0.19). Some of the documented delayed reasons were referral patterns, socioeconomic burden or functional status. There was no difference in PFS between the two cohorts. However, when only patients with IIB or higher disease were included, there was a trend towards an increase in mean PFS favoring treatment at our institution (113 wk vs 75 wk, P = 0.1). 77% of patients had HDR boost delayed more than 7 days after completion of EBRT when treated at an OF in comparison to 18% of the patients in our institution (P < 0.01). Of the women with positive lymph nodes (FIGO Stage IIIC1 or C2) treated at an OF, only 19% received nodal irradiation boost compared to 89% in our institution. All patients with FIGO Stage IIIC2 received EFRT in our institution.Women with locally advanced cervical cancer in rural areas are less likely to complete the total radiation treatment in less than eight weeks due to socioeconomic disparities, health access or inappropriate referral patterns. This increased delay translated to a trend in survival when examining women with higher stage cancer. Improving access to brachytherapy and external beam radiotherapy at specialized high volume referral centers may improve patient outcomes.

Prognostic significance of uPA and uPAR expression in patients with cervical cancer undergoing radiotherapy.

Cervical cancer remains a major health threat. Urokinase serves as a marker of metastatic tumors. The present study aimed to determine whether the expression levels of urokinase plasminogen activator (uPA) and urokinase plasminogen activator receptor (uPAR), before and during the course of radiotherapy, serve as prognostic markers for patients with cervical cancer. Cervical tumor tissue biopsies were collected from 72 patients before radiotherapy and after the completion of external beam radiotherapy (EBRT) before intracavitary brachytherapy. The levels of uPA and uPAR were determined using ELISA assays. The significance of the associations between the protein expression levels and the clinical outcomes of patients was determined. Although irradiation enhanced uPA and uPAR expression in cervical cancer cell lines, average uPA levels significantly decreased in tumors, and uPAR levels significantly increased after EBRT. The levels of uPA increased in 12 patients and decreased in 26 patients; and those of uPAR increased in 13 patients and decreased in two patients. Cox regression analysis revealed that increased expression of uPAR was significantly associated with 5-year overall survival rate [hazard ratio (HR), 3.65; 95% confidence interval (CI), 1.18–11.30]. However, the levels of both proteins before radiotherapy failed to predict clinical outcomes. Other significant predictive factors were partial response (HR 7.22; 95% CI 1.17–44.73) and disease progression (HR, 13.41; 95% CI, 1.17–153.07). These findings indicated that increased expression of uPAR in cervical tumor tissue during radiotherapy may serve as a prognostic marker for patients with cervical cancer.

Modified Houdek vault applicator for high-dose-rate brachytherapy: a technical report and case series.

PurposeTreatment of isolated post-surgical vault recurrence of cervical and endometrial cancers in previously unirradiated patients includes external beam radiotherapy (EBRT) ± concomitant chemotherapy, followed by brachytherapy (BT) boost. Supra-vaginal component of vault disease often requires interstitial BT for optimal dose coverage. We describe technical details and preliminary case series using modified Houdek vault applicator (MHVA) developed at our institution for limited intra-cavitary plus interstitial high-dose-rate (HDR) vault BT.Material and methodsNineteen patients with vaginal vault recurrences received BT boost with MHVA between October 2015 and May 2018. All underwent BT application and CT-based BT planning after completion of EBRT ± concomitant chemotherapy.ResultsMedian EQD2 of BT dose in patients with carcinoma cervix recurrence (n = 15, α/β = 10) was 18.8 Gy, and in those with endometrial cancer recurrence was 22.08 Gy (n = 4, α/β = 4.5). Median total EQD2 was 68.8 Gy and 72.08 Gy, respectively. Mean 2 cc of bladder, rectum, and sigmoid EBRT + BT doses (EQD2, α/β = 3) were 65.38 Gy (±7.76), 63.37 Gy (±5.52), and 57.04 Gy (±4.45), respectively. At 6-8 weeks, 17 patients showed complete response (CR). With median follow-up of 20.5 months, 2-year overall survival was 95% (95% CI: 85.2-100.0%), and 2-year progression-free survival was 79.4% (95% CI: 61.0-97.8%). Late toxicities seen were grade 2 proctitis in 1 patient, grade 1 proctitis in 5, grade 2 urethritis in 1, grade 3 cystitis in 1, and recto-vaginal fistula in 1 patient (with disease controlled). Recurrence rate was 6.7 times higher in patients with post-EBRT disease greater than 10 mm (p = 0.01).ConclusionsMHVA is a simple solution for intra-cavitary and interstitial HDR-BT boost in isolated vault cancers post-surgery, achieving acceptable dosimetric parameters. Preliminary clinical outcomes and late toxicities are satisfactory.

The use of hyperbaric oxygen to treat actinic rectal fistula after SpaceOAR use and radiotherapy for prostate cancer: a case report

BackgroundIn definitive radiation therapy for prostate cancer, the SpaceOAR® System, a hydrogel spacer, is widely used to decrease the irradiated dose and toxicity of rectum. On the other hand, periprostatic abscesses formation and rectal perforation are known as rare adverse effects of SpaceOAR. Nevertheless, there is a lack of reports clarifying the association between aggravation of abscesses and radiation therapy, and hyperbaric oxygen therapy (HBOT) is effective for a peri-SpaceOAR abscess and rectal perforation.Case presentationWe report a case of a 78-year-old high-risk prostate cancer patient. After SpaceOAR insertion into the correct space, he started to receive external beam radiation therapy (EBRT). He developed a fever, perineal pain and frequent urination after the completion of EBRT, and the magnetic resonance imaging (MRI) revealed a peri-SpaceOAR abscess. Scheduled brachytherapy was postponed, administration of antibiotics and opioid via intravenous drip was commenced, and transperineal drainage was performed. After the alleviation of the abscess, additional EBRT instead of brachytherapy was performed with MRI-guided radiation therapy (MRgRT). On the last day of the MRgRT, perineal pain reoccurred, and MRI and colonoscopy detected the rectal perforation. He received an intravenous antibiotics drip and HBOT, and fully recovered from the rectal perforation.ConclusionsOur report indicates that EBRT can lead to a severe rectum complication by causing inflammation for patients with a peri-SpaceOAR abscess. Furthermore, HBOT was effective for the peri-SpaceOAR abscess and rectal perforation associated with EBRT.

Intracavitary plesiotherapy as boost treatment in a patient of cancer cervix

Purpose: Mold brachytherapy is an age old treatment for superficial tumors. Vaginal mold brachytherapy for gynecological malignancies of vaginal vault and vagina is being practiced in different institutes across the globe. We are reporting the technical aspects of vaginal mold and optimal treatment to the patient. Materials and Methods: This is a case of Carcinoma Cervix International Federation of Gynaecology and Obstetrics st-IIIA(lower one-third vaginal involvement) with residual disease in the anterior wall of lowerd one-third of vagina after the completion of external beam radiotherapy. The patient was reluctant for interstitial implant brachytherapy and hence was planned for vaginal mold brachytherapy with an aim to boost residual tumor. Five stainless steel Implant needles attached to the sorbo from 9'o clock to 3'o clock position with adequate spacing between the needles. Modeling wax, which is nearly tissue equivalent, was used for making mold. The material was molded into a cast cylindrically over the needles and sorbo homogeneously taking care that there were no air gaps. After taking aseptic precautions the cylindrical mold with needles and sorbo was inserted into the vaginal cavity and stabilized with a T-bandage. Computed tomography scan was performed and images were imported to treatment planning system. Clinical target volume was contoured along with organs at risk (bladder and rectum) and geometric optimization was done to obtain proper dwell times and positions where the D90was kept at 100% of the prescribed dose. Conclusion: Vaginal mold brachytherapy may be used as an alternative technique to interstitial implant brachytherapy as a boost treatment in vaginal malignancies. Patient-specific mold brachytherapy technique can be used in the cases where the target volume is superficial and limited to vagina. It is a minimally invasive technique which mimics the dose distribution of interstitial brachytherapy.