Evaluation of liver segmental dose threshold for hepatocyte regeneration following liver stereotactic body radiation therapy.

BACKGROUND OBJECTIVES: There is limited evidence studying the relationship of liver segmental dose and segmental volume changes. The segmental dose thresholds could potentially allow for segmental regeneration after liver stereotactic body radiation therapy (SBRT). Given improved survival in hepatocellular cancer (HCC) and liver metastases and more salvage therapy options, this has become an important clinical question to explore. This study assesses the impact of liver segmental dose on segmental volume changes (gain or loss) after SBRT. METHODS: Liver segmental contours were delineated on baseline and serial follow up triphasic computed tomography scans. The volumes of total liver and doses to total liver, uninvolved liver and individual segments were noted. A correlation was evaluated between liver/segmental volume and dose using Pearson's correlation. Furthermore, receiver operator's curve (ROC) analysis was performed to find the segmental dose, i.e . predictive for liver volume loss. RESULTS: A total of 140 non-tumour liver segments were available for analysis in 21 participants. Overall, 13 participants showed loss of overall liver volume and eight showed gain of overall liver volume. The median dose in segments reporting an increase in volume was 9.1 Gy (7-36 Gy). The median dose in segments losing volume was 15.5 Gy (1-49 Gy). On ROC analysis, segmental dose >11 Gy was associated with volume loss. On univariate analysis, only liver segmental dose contributed to a significant segmental volume loss. INTERPRETATION CONCLUSIONS: We propose from the findings of this study that in SBRT for large hepatocellular cancer or liver metastases, liver segments should be individually delineated. Furthermore, 3-5 liver segments may be preferentially subjected to <9 Gy to facilitate hepatocyte regeneration. Preferential sparing of uninvolved liver segments may improve outcomes in liver stereotaxyas lower segmental doses were associated with liver regeneration. This may have implications on future liver SBRT planning where segmental doses may be as important as the mean dose.

Temporal course of late rectal toxicity & impact of intervention in patients undergoing radiation for cervical cancer.

BACKGROUND & OBJECTIVES: : There is limited information available on the temporal course of late stage radiotherapy adverse effects. The present study reports on the temporal course of late toxicities after chemoradiation and brachytherapy. METHODS: : Women with cervical cancer who presented with late toxicity after (chemo) radiation were included in the study. Grade of toxicity (Clinical Toxicity Criteria for Adverse Events version 4.03) and type of intervention were recorded at three-monthly interval for the first year and then six monthly until 24 months. Direct cost for the management of toxicity was calculated. Univariate analysis was performed to understand the impact of various factors on persistence of toxicity. RESULTS: : Ninety two patients were included in this study. Grades I, II, III and IV toxicities were observed in 50 (54%), 33 (36%), 7 (8%) and 2 (2%) patients, respectively, at first reporting. Patients spent a median of 12 (3-27) months with toxicity. At 12 months, 48/92 (52.2%) patients had a complete resolution of toxicity, whereas 27/92 (29.3%) patients had low grade (I-II) persistent toxicity. Only 6/92 (6.5%) patients who had grade III-IV toxicity had resolution to a lower grade. Four (4.3%) patients died due to toxicity. At 24 months, 9 (10%) patients continued to have grade ≥ III toxicity. On an average, 7 (2-24) interventions were required for the clinical management of late toxicity and median direct cost incurred was ₹ 50,625 (1,125-303,750). INTERPRETATION & CONCLUSIONS: : In this study late radiation toxicity resolved within 12 months in more than half of patients. However, others are likely to have had persistent lower grade toxicity or progression to higher grade. Structured strategies are hence needed for the effective management of late toxicities.

The IAEA remote audit of small field dosimetry for testing the implementation of the TRS-483 code of practice.

BACKGROUND: The TRS­483, an IAEA/AAPM International Code of Practice on dosimetry of small static photon fields, underwent testing via an IAEA coordinated research project (CRP). Alongside small field output factors (OFs) measurements using active dosimeters by CRP participants, the IAEA Dosimetry Laboratory received a mandate to formulate a remote small field dosimetry audit method using its passive dosimetry systems. PURPOSE: This work aimed to develop a small field dosimetry audit methodology employing radiophotoluminescent dosimeters (RPLDs) and radiochromic films. The methodology was subsequently evaluated through a multicenter pilot study with CRP participants. METHODS: The developments included designing and manufacturing a dosimeter holder set and the characterization of an RPLD system for measurements in small photon fields using the new holder. The audit included verification of small field OFs and lateral beam profiles for small fields. At first, treatment planning system (TPS) calculated OFs were checked against a reference data set that was available for conventional linacs. Second, calculated OFs were verified through the RPLD measurement of point doses in a machine-specific reference field, 4 cm × 4 cm, 2 cm × 2 cm, and 1 cm × 1 cm, corresponding size circular fields or nearest achievable field sizes. Lastly, profile checks in in-plane and cross-plane directions were done for the two smallest fields by comparing film measurements with TPS calculations at 20%, 50%, and 80% isodose levels. RESULTS: RPLD correction factors for small field measurements were approximately unity. However, they influenced the dose determination's overall uncertainty in small fields, estimated at 2.30% (k = 1 level). Considering the previous experience in auditing reference beam output following the TRS-398 Code of Practice, the acceptance limit of 5% for the ratio of the dose determined by RPLD to the dose calculated by TPS, DRPLD/DTPS, was considered adequate. The multicenter pilot study included 15 participants from 14 countries (39 beams). Consistent with the previous findings, the results of the OF check against the reference data confirmed that TPSs tend to overestimate OFs for the smallest fields included in this exercise. All except three RPLD measurement results were within the acceptance limit, and the spread of results increased for smaller field sizes. The differences between the film measured and TPS calculated dose profiles were within 3 mm for most of the beams checked; deviated results revealed problems with TPS commissioning and calibration of the treatment unit collimation systems. CONCLUSION: The newly developed small field dosimetry audit methodology proved effective and successfully complemented the CRP OF measurements by participants with RPLD audit results.

Sigmoid dose accumulation and reporting for multifractionated brachytherapy for cervical cancer: Methodological development of sigmoid points through virtual endoscopic method.

PURPOSE: The sigmoid is an important organ at risk for gynecological brachytherapy (BT). However, the reliability of localization of high-dose regions during multi-fractionated treatment is limited. This work reports the methodological development of sigmoid points to summate multi-fractionated doses. METHODS AND MATERIAL: Ten paired MRI data sets of ring-based intracavitary brachytherapy were obtained. Simulating a virtual endoscope, a reference line was created along the central axis of the anorectosigmoid for each implant. A trendline was generated, and linear dose was determined. Three-dimensional (3D) coordinates of high-dose regions were identified, and overlap was determined. In the next step, 3D coordinates of high-dose sigmoid points were localized in reference to cervical os and re-verified for location in reference to sigmoid lumen and corroboration with 2cc doses. With minor modifications, sigmoid points were proposed. RESULTS: In 6 of 10 patients, high-dose regions co-localized in subsequent fractions of BT. Three high-dose regions were identified along the sigmoid length and proposed as sigmoid points in reference to cervical os. (S1'= 0.5 cm right, 1.5 cm posterior, and 2.4 cm cranial; S2' = 0.3 cm anterior and 4.5 cm cranial; S3' = 2.7 cm left, 3 cm anterior, and 3.6 cm cranial to the cervical os). S1' and S2' were located in the sigmoid in 70% and 60% of data sets. The mean difference between D2cc and S1'/S2' was 0.30 Gy and 1.06 Gy respectively. S3' had limited corroboration to sigmoid lumen or 2 cc doses. The points S1' and S2' were further modified (minor) for applicability and proposed as sigmoid points 1 and 2 (SP1 0.5 right,1.5 posterior and 2.5 cm cranial to cervical os and SP2 (0.5 cm anterior and 4.5 cm cranial to cervical os)). CONCLUSION: SP1 and SP 2 are proposed as a surrogate for 2 cc sigmoid doses and may provide a method of reliable inter-fraction dose summation. This pilot work requires further validation.

IAEA/WHO postal dosimetry audit methodology for electron beams using radio photoluminescent dosimeters.

BACKGROUND: Independent dosimetry audits are an important intervention in radiotherapy for quality assurance. Electron beams, used for superficial radiotherapy treatments, must also be tested in dosimetry audits as part of a good quality assurance program to help prevent clinical errors. PURPOSE: To establish a new service for IAEA/WHO postal dosimetry audits in electron beams using RPL dosimeters. METHODS: A novel postal audit methodology employing a PMMA holder system for RPLDs was developed. The associated correction factors including holder dependence, energy dependence, dose response non-linearity, and fading were obtained and tested in a multi-center (n = 12) pilot study. A measurement uncertainty budget was estimated and employed in analyzing the irradiated dosimeters. RESULTS: Holder and energy correction factors ranged from 1.004 to 1.010 and 1.019 to 1.059 respectively across the energy range. The non-linearity and fading correction models used for photon beams were tested in electron beams and did not significantly increase measurement uncertainty. The mean dose ratio ± SD of the multi-center study was 1.001 ± 0.011. The overall uncertainty budget was estimated as ± 1.42% (k = 1). CONCLUSIONS: A methodology for IAEA/WHO postal dosimetry audits in electron beams was developed and validated in a multi-center study and is now made available to radiotherapy centers as a routine service.

Can knowledge based treatment planning of VMAT for post-mastectomy locoregional radiotherapy involving internal mammary chain and supraclavicular fossa improve performance efficiency?

Introduction: To validate and evaluate the performance of knowledge-based treatment planning for Volumetric Modulated Arc Radiotherapy for post-mastectomy loco-regional radiotherapy. Material and methods: Two knowledge-based planning (KBP) models for different dose prescriptions were built using the Eclipse RapidPlanTM v 16.1 (Varian Medical Systems, Palo Alto, USA) utilising the plans of previously treated patients with left-sided breast cancer who had undergone irradiation of the left chest wall, internal mammary nodal (IMN) region and supra-clavicular fossa (SCF). Plans of 60 and 73 patients were used to generate the KBP models for the prescriptions of 40 Gy in 15 fractions and 26 Gy in 5 fractions, respectively. A blinded review of all the clinical plans (CLI) and KBPs was done by two experienced radiation oncology consultants. Statistical analysis of the two groups was also done using the standard two-tailed paired t-test or Wilcoxon signed rank test, and p<0.05 was considered significant. Results: A total of 20 metrics were compared. The KBPs were found to be either better (6/20) or comparable (10/20) to the CLIs for both the regimens. Dose to heart, contralateral breast,contralateral lung were either better or comparable in the KBP plans except of ipsilateral lung. Mean dose (Gy) for the ipsilateral lung are significantly (p˂0.001) higher in KBP though the values were acceptable clinically. Plans were of similar quality as per the result of the blinded review which was conducted by slice-by-slice evaluation of dose distribution for target coverage, overdose volume and dose to the OARs. However, it was also observed that treatment times in terms of monitoring units (MUs) and complexity indices are more in CLIs as compared with KBPs (p<0.001). Discussion: KBP models for left-sided post-mastectomy loco-regional radiotherapy were developed and validated for clinical use. These models improved the efficiency of treatment delivery as well as work flow for VMAT planning involving both moderately hypo fractionated and ultra-hypo fractionated radiotherapy regimens.

The American Brachytherapy Society and Indian Brachytherapy Society consensus statement for the establishment of high-dose-rate brachytherapy programs for gynecological malignancies in low- and middle-income countries.

PURPOSE: The global cervical cancer burden is disproportionately high in low- and middle-income countries (LMICs), and outcomes can be governed by the accessibility of appropriate screening and treatment. High-dose-rate (HDR) brachytherapy plays a central role in cervical cancer treatment, improving local control and overall survival. The American Brachytherapy Society (ABS) and Indian Brachytherapy Society (IBS) collaborated to provide this succinct consensus statement guiding the establishment of brachytherapy programs for gynecological malignancies in resource-limited settings. METHODS AND MATERIALS: ABS and IBS members with expertise in brachytherapy formulated this consensus statement based on their collective clinical experience in LMICs with varying levels of resources. RESULTS: The ABS and IBS strongly encourage the establishment of HDR brachytherapy programs for the treatment of gynecological malignancies. With the consideration of resource variability in LMICs, we present 15 minimum component requirements for the establishment of such programs. Guidance on these components, including discussion of what is considered to be essential and what is considered to be optimal, is provided. CONCLUSIONS: This ABS/IBS consensus statement can guide the successful and safe establishment of HDR brachytherapy programs for gynecological malignancies in LMICs with varying levels of resources.

Dose Accumulation for Multicourse Gynecological Reirradiation: A Methodological Narrative and Clinical Examples.

PURPOSE: Reirradiation (re-RT) is a suitable and potentially curative treatment option for in-field locoregional recurrences in gynecological malignancies. Lack of clear guidelines on prescription, dose-response relationship, and clinical outcomes limits its clinical use. This clinical narrative describes the methodology for integration of deformable image registration (DIR) for cumulative dose assessment in the setting of re-RT for gynecologic malignancies, using the tools available within a commercial treatment planning system. METHODS AND MATERIALS: Four patients who received re-RT for locoregional recurrence or second cancer within previously irradiated areas for a gynecologic primary were identified. Patient-specific DIR for deformable dose mapping and accumulation was retrospectively performed using intensity-based algorithm provided by the Varian Medical Systems Velocity AI version 4.1. Cumulative equivalent doses in 2 Gy fractions (EQD2) delivered to overlapping targets and organs at risk were generated and compared with the physically summated doses. For both approaches, brachytherapy (BT) component was physically summated in cases where the BT applicator caused significant anatomic distortion. RESULTS: The mean maximum cumulative overlapping target dose was 119.4 Gy10 (range, 84.7 Gy10-144.9 Gy10). The mean cumulative doses received by 2 cm3 of bladder, rectum, sigmoid, and bowel were 114.6 Gy3 (101.1-133.4 Gy3), 98.7 Gy3 (67-136.2 Gy3), 92.5 Gy3 (70.4-107 Gy3), and 89.9 Gy3 (81.1-102.8 Gy3), respectively. In the setting of in-field nodal recurrence, DIR-based dose summation was associated with lower cumulative organs at risk doses than those estimated with physical summation, except in one case with a higher bowel dose. In cases where re-RT was given for local recurrence/second primary, variation in sigmoid doses was observed between the 2 dose-summation strategies across all 3 cases, but it was inconsistent with bladder, rectum, or the bowel. CONCLUSIONS: DIR-based dose accumulation can be used to guide re-RT planning and can provide clinically relevant information, especially in cases with nodal recurrences. Registration of BT data sets remain challenging and requires an individualized assessment when applying these algorithms to clinical practice.

Using Artificial Intelligence for Optimization of the Processes and Resource Utilization in Radiotherapy.

The radiotherapy (RT) process from planning to treatment delivery is a multistep, complex operation involving numerous levels of human-machine interaction and requiring high precision. These steps are labor-intensive and time-consuming and require meticulous coordination between professionals with diverse expertise. We reviewed and summarized the current status and prospects of artificial intelligence and machine learning relevant to the various steps in RT treatment planning and delivery workflow specifically in low- and middle-income countries (LMICs). We also searched the PubMed database using the search terms (Artificial Intelligence OR Machine Learning OR Deep Learning OR Automation OR knowledge-based planning AND Radiotherapy) AND (list of Low- and Middle-Income Countries as defined by the World Bank at the time of writing this review). The search yielded a total of 90 results, of which results with first authors from the LMICs were chosen. The reference lists of retrieved articles were also reviewed to search for more studies. No language restrictions were imposed. A total of 20 research items with unique study objectives conducted with the aim of enhancing RT processes were examined in detail. Artificial intelligence and machine learning can improve the overall efficiency of RT processes by reducing human intervention, aiding decision making, and efficiently executing lengthy, repetitive tasks. This improvement could permit the radiation oncologist to redistribute resources and focus on responsibilities such as patient counseling, education, and research, especially in resource-constrained LMICs.

Dosimetric impact of target definition in brachytherapy for cervical cancer - Computed tomography and trans rectal ultrasound versus magnetic resonance imaging.

Background and Purpose: Magnetic Resonance Imaging (MRI) based target definition in cervix brachytherapy is limited by its availability, logistics and financial implications, therefore, use of computed tomography (CT) and Trans Rectal UltraSonography (TRUS) has been explored. The current study evaluated the dosimetric impact of CT + TRUS based target volumes as compared to gold standard MRI. Methods and Materials: Images of patients (n = 21) who underwent TRUS followed by MRI and CT, were delineated with High-Risk Clinical Target Volume in CT (CTVHR-CT) and in MRI (CTVHR-MR). CTVHR-CT was drawn on CT images with TRUS assistance. For each patient, two treatment plans were made, on MRI and CT, followed by fusion and transfer of CTVHR-MR to the CT images, referred as CTVHR-MRonCT. The agreement between CTVHR-MRonCT and CTVHR-CT was evaluated for dosimetric parameters (D90, D98 and D50; Dose received by 90%, 98% and 50% of the volumes) using Bland-Altman plots, linear regression, and Pearson correlation. Results: No statistically significant systematic difference was found between MRI and CT. Mean difference (±1.96 SD) of D90, D98 and D50 between CTVHR-MRonCT and CTVHR-CT was 2.0, 1.2 and 5.6 Gy respectively. The number of patients who have met the dose constraints of D90 > 85 Gy were 90% and 80% in MR and in CT respectively, others were in the borderline, with a minimum dose of 80 Gy. The mean ± SD dose-difference between MR and CT plans for bladder was significant (5 ± 13 Gy; p = 0.12) for D0.1cm3, while others were statistically insignificant. Conclusion: CT + TRUS based delineation of CTVHR appear promising, provide useful information to optimally utilize for brachytherapy planning, however, MRI remains the gold standard.

Reporting and validation of gynaecological Groupe Euopeen de Curietherapie European Society for Therapeutic Radiology and Oncology (ESTRO) brachytherapy recommendations for MR image-based dose volume parameters and clinical outcome with high dose-rate brachytherapy in cervical cancers: a single-institution initial experience.

OBJECTIVE: The objectives are to report the dosimetric analysis, preliminary clinical outcome, and comparison with published data of 3-dimensional magnetic resonance-based high dose rate brachytherapy (BT) in cervical cancer. MATERIALS AND METHODS: The data set of 24 patients with cervical cancer treated with high dose-rate brachytherapy applications was analyzed. All patients received radiation with or without chemotherapy (10 patients received concomitant chemoradiation). Point A, International Commission on Radiation Units and Measurement (ICRU) point doses, and Groupe Europeen de Curietherapie-European Society for Therapeutic Radiology and Oncology dose volume parameters, namely, high-risk clinical target volume (HR-CTV), D90 and D100 doses, and dose to D0.1cc and D2cc, for rectum, bladder, and sigmoid, were calculated and correlated. RESULTS: Mean ± SD HR-CTV was 45.2 ± 15.8 cc. The mean ± SD point A dose was 73.4 ± 4.5 Gy (median, 74.3 Gy) total biologically equivalent dose in 2 Gy per fraction (EQD2), whereas mean ± SD D90 doses were 70.9 ± 10.6 GyEQD2 (median, 68). The mean ± SD ICRU rectal and bladder points were 63.5 ± 8.1 and 80.4 ± 34.4 GyEQD2, respectively. The D0.1cc and D2cc for rectum were 66.0 ± 9.9 GyEQD2 (median, 64.5) and 57.8 ± 7.7 GyEQD2 (median, 58.8), for bladder 139.1 ± 54.7 GyEQD2 (median, 131.9) and 93.4 ± 24.6 GyEQD2 (median, 91), and sigmoid were 109.4 ± 45.2 GyEQD2 (median, 91) and 74.6 ± 19.6 GyEQD2 (median, 69.6). With a median follow-up of 24 months, 3 patients had local nodal failure, 1 had right external iliac nodal failure, and 1 had left supraclavicular nodal failure. CONCLUSIONS: The 3-D magnetic resonance image-based high dose-rate brachytherapy approach in cervical cancers is feasible. In our experience, the HR-CTV volumes are large, and D0.1cc and D2cc doses to bladder and sigmoid are higher than published literature so far.

Low-Dose-Rate versus High-Dose-Rate intracavitary brachytherapy in cervical cancer - Final Results of a Phase III randomized trial.

PURPOSE: Intracavitary brachytherapy using High-Dose-Rate (HDR) and Low-dose-rate (LDR) in cervical cancer has been utilized. We report the long-term final results of a large randomized trial in terms of toxicities and efficacy. METHODS AND MATERIALS: Between 1996 to 2005, 816 patients were randomized to LDR (n = 441 patients) or HDR brachytherapy (n = 369 patients) stratified by FIGO Stage grouping. Patients with Stage I-II received external irradiation of 40 Gy in 20 fractions (with midline block (MLB)) followed by either 2 LDR Intracavitary applications of 30 Gy to point A (2-3 weeks apart) or 5 HDR Intracavitary applications of 7 Gy to point A once weekly. Patients with Stage III received 50 Gy in 25 fractions (with MLB after 40 Gy) followed by either one application of LDR 30 Gy to point A or three applications of HDR 7 Gy to point A once weekly. RESULTS: With a median follow-up was 64 months (interquartile range [IQR]: 21 - 111), moderate to severe rectal and bladder complications were higher in LDR arm as compared to HDR arm (9.7% vs. 3.6%; p = 0.02) and (10.5% vs. 5.5%; p = 0.06) for Stage I-II. No difference in rectal or bladder complications for Stage III patients. Disease free and overall survivals were similar in both the arms for all stages. CONCLUSIONS: HDR intracavitary brachytherapy with 7 Gy per fraction weekly is superior to LDR in terms of late rectal and bladder complications. Local control rates and survivals are similar irrespective of stages.

Implementation of a visual feedback system for motion management during radiation therapy.

PURPOSE: To describe the details of an in-house video goggles feedback system assembled from several commercially available components. The objective of this paper is to share our experience with this system, provide details on the equipment needed, system assembly, patient set up and user settings on some components. MATERIALS AND METHODS: The system consisted of goggles (FPView3DHD, ITV, USA), RJ45(Registered Jack) to Digital Visual Interface (DVI) converter (Tripplite), DVI to HDMI converters, Local Area Network(LAN) cable, HDMI and power extender cables. The video coaching system was implemented both in CT simulator (GE Discovery)) and in treatment delivery machine True Beam v2.1 Varian Medical Systems (VMS, Palo Alto), which was integrated with respiratory motion management (RPM V 1.7.5) system. RESULTS: The video feedback system is in clinical use since Aug 2017, so far, we have treated 13 patients, with approximately 150 fractions. The performance of the device was found to be satisfactory. All the patients were coached for DIBH and the usage of the goggles, which includes wearing the goggles, display details of the monitor, and the threshold levels of the breathing wave cycle. The patients understand the instructions very well and hence regulate the breathing cycle, which improves the treatment accuracy and efficiency. CONCLUSION: Video feedback system for motion management, for patients undergoing radiotherapy was implemented successfully both in CT simulator and in linear accelerator.

Reporting of dose-volume specifications for "Martinez Universal Perineal Interstitial Template-based interstitial high-dose-rate brachytherapy for gynecological cancers" according to International Commission on Radiation Units and Measurements 58 with early clinical outcomes.

PURPOSE: The study is an audit of reporting dose and volume specifications as per the ICRU 58 for MUPIT-based interstitial brachytherapy in gynecological cancers. Correlation between total reference air kerma (TRAK) and isodose surface was also evaluated to understand the intensity of treatment in interstitial brachytherapy. METHODS AND MATERIALS: Forty-two patients underwent HDR MUPIT-based interstitial brachytherapy 20 Gy in five fractions after EBRT during 2017-2019. Treated volume, high and low-dose regions, mean central dose, Dose Homogeneity Index (DHI), organ at risk doses, and TRAK values were computed. RESULTS: High-dose regions V150 mean was 12.4 cc and V200 was 4.58 cc; and low-dose region was 75.92 cc. The mean treated volume was 59.8 cc. The mean central dose was 3.7 Gy. DHI was 79%. The mean D2cm3 bladder and rectum were 2.9 Gy and 2.8 Gy. The mean TRAK was 0.16 cGy per fraction per hour at 1 m. TRAK values showed significant correlation with various isodose volumes (TRAK and V100: r = 0.943 p < 0.0005; and TRAK and V50: r = 0.953; p < 0.0005). A positive correlation was observed between TRAK and the number of needles (r = 0.746; p < 0.0005). At a median followup of 16 months, 4 of 42 patients (9.5%) had local recurrences. CONCLUSIONS: Our study shows compliance with ICRU 58 recommendations along with certain deviations. Local recurrence rate is acceptable. TRAK shows correlation with surface isodose in MUPIT-based brachytherapy and should to be evaluated in future studies.

Effect of COVID-19 Pandemic on Gynecological Cancer Radiation During Complete Nationwide Lockdown: Observations and Reflections From Tertiary Care Institute in India.

PURPOSE: To report real-world compliance to radiation in gynecologic cancers during the complete lockdown phase of COVID-19 pandemic. METHODS AND MATERIALS: From March 23, 2020, until June 30, 2020, complete lockdown was imposed in India. During this period there was restructuring of cancer care and radiation oncology department due to operational policies prevalent in the institution, and the care for gynecological cancer was based on the evolving international recommendations. Institutional review board approval was obtained to audit patterns of care during the complete lockdown phase. Descriptive variables were used to report on patient characteristics, compliance, delays, toxicity, and observed deviations in recommended care. RESULTS: During the lockdown period spanning 100 days, treatment of 270 and telephonic follow-up of 1103 patients with gynecological cancer was undertaken. Of 270 new patients, due to travel restrictions, 90 patients were referred to the facilities in vicinity of their residence. Of the remaining 180 patients, 138 were planned for complete treatment at our institution and 42 were referred to our center for brachytherapy. Of 138 patients, only 106 (76%) completed the planned external radiation. Twenty-four (26%) patients completed full course of concurrent chemotherapy, 11 (12%) received chemotherapy dose reduction, and 57 (62%) received no concurrent chemotherapy. Treatment delay of up to 3 weeks was noted in 8.6% patients due to COVID-19 infection. No grade 4 to 5 acute sequelae were observed. No excess adverse effects were observed in high-risk population. Low rate of symptom burden was observed among 1103 patients on telephonic follow-up. With 100 (9.6%) patients reporting symptoms, among these, 54% (54 of 100) had complete resolution of symptoms within 4 weeks of teleconsultation, and 10% had disease progression. CONCLUSIONS: Low compliance with planned treatment was observed for radiation and concurrent chemotherapy due to lockdown and fear of contracting COVID-19 and will likely lead to increased risk of cancer-related mortality. Rapid restructuring of care is needed to prevent the same as COVID-19 pandemic further evolves.

Development and clinical validation of Knowledge-based planning for Volumetric Modulated Arc Therapy of cervical cancer including pelvic and para aortic fields.

BACKGROUND AND PURPOSE: Knowledge-based planning (KBP) is based on a model to estimate dose-volume histograms, configured using a library of historical treatment plans to efficiently create high quality plans. The aim was to report configuration and validation of KBP for Volumetric Modulated Arc Therapy of cervical cancer. MATERIALS AND METHODS: A KBP model was configured from the institutional database (n = 125), including lymph node positive (n = 60) and negative (n = 65) patients. KBP Predicted plans were compared with Clinical Plans (CP) and Re-plans (Predicted plan as a base-plan) to validate the model. Model quality was quantified using coefficient of determination R2, mean square error (MSE), standard two-tailed paired t-test and Wilcoxon signed rank test. RESULTS: Estimation capability of the model was good for the bowel bag (MSE = 0.001, R2 = 0.84), modest for the bladder (MSE = 0.008) and poor for the rectum (MSE = 0.02 R2 = 0.78). KBP resulted in comparable target coverage, superior organ sparing as compared to CP. Re-plans outperformed CP for the bladder, V30 (66 ± 11% vs 74 ± 11%, p < .001), V40 (48 ± 14% vs 52 ± 14%, p < .001), however sparing was modest for the bowel bag V30 (413 ± 191cm3 vs 445 ± 208cm3, p = .037) V40 (199 ± 105cm3 vs 218 ± 127cm3, p = .031). All plans were comparable for rectum, while KBP resulted in significant sparing for spinal cord, kidneys and femoral heads. CONCLUSION: KBP yielded comparable and for some organs superior performance compared to CP resulting in conformal and homogeneous target coverage. Improved organ sparing was observed when individual patient geometry was considered.

Late Toxicity After Adjuvant Conventional Radiation Versus Image-Guided Intensity-Modulated Radiotherapy for Cervical Cancer (PARCER): A Randomized Controlled Trial.

PURPOSE: Postoperative Adjuvant Radiation in Cervical Cancer (PARCER), a phase III randomized trial, compared late toxicity after image-guided intensity-modulated radiotherapy (IG-IMRT) with three-dimensional conformal radiation therapy (3D-CRT) in women with cervical cancer undergoing postoperative radiation. METHODS: Patients were randomly assigned to receive either IG-IMRT or 3D-CRT after stratification for the type of hysterectomy and use of concurrent chemotherapy. The primary end point was 3-year grade ≥ 2 late GI toxicity assessed using Common Toxicity Criteria for Adverse Events v 3.0 and estimated using time-to-event, intention-to-treat analysis, with a study level type I error of 0.05 and a nominal α of .047 after accounting for one interim analysis. Secondary end points included acute toxicity, health-related quality of life, and pelvic relapse-free, disease-free, and overall survival. RESULTS: Between 2011 and 2019, 300 patients were randomly assigned (IG-IMRT 151 and 3D-CRT 149). At a median follow-up of 46 (interquartile range, 20-72) months, the 3-year cumulative incidence of grade ≥ 2 late GI toxicity in the IG-IMRT and 3D-CRT arms were 21.1% versus 42.4% (hazard ratio [HR] 0.46; 95% CI, 0.29 to 0.73; P < .001). The cumulative incidence of grade ≥ 2 any late toxicity was 28.1% versus 48.9% (HR 0.50; 95% CI, 0.33 to 0.76; P < .001), respectively. Patients reported reduced diarrhea (P = .04), improved appetite (P = .008), and lesser bowel symptoms (P = .002) with IG-IMRT. However, no difference was observed in the time by treatment interaction. The 3-year pelvic relapse-free survival and disease-free survival in the IG-IMRT versus the 3D-CRT arm were 81.8% versus 84% (HR 1.17; 95% CI, 0.68 to 1.99; P = .55) and 76.9% versus 81.2% (HR 1.03; 95% CI, 0.62 to 1.71; P = .89), respectively. CONCLUSION: IG-IMRT results in reduced toxicity with no difference in disease outcomes.

Image registration, contour propagation and dose accumulation of external beam and brachytherapy in gynecological radiotherapy.

This review provides an overview of the current status of image registration for image guided gynaecological brachytherapy including combination with external beam radiotherapy. Contour propagation between individual fractions and dose accumulation can be useful for cervix cancer radiotherapy. Contour mapping and applicator reconstruction with rigid registration based on the applicator geometry provide good accuracy. However, deformable image registration is particularly challenging in the pelvic region, due to the large and complex deformations caused by tumor shrinkage, bladder and rectum filling, insertion of a brachytherapy applicator and presence of packing material. This causes substantial limitations and uncertainties when using it in the clinical workflow so that the current generation of deformable image registration algorithms is not yet robust enough to handle complexities involving the dose accumulation of external beam and brachytherapy. The direct addition of doses provides a reasonable estimate of the total absorbed dose. However, in case of significant dose gradients from external beam boosts or midline-shielding adding dose contributions from the different radiotherapy modalities and fractions remains subject to large uncertainties.

FIGO Classification 2018: Validation Study in Patients With Locally Advanced Cervix Cancer Treated With Chemoradiation.

PURPOSE: In 2018, the International Federation of Gynecology and Obstetrics (FIGO) proposed a new staging for cervical cancer. The present study was designed to reclassify patients with locally advanced cervix cancer and perform a comparative evaluation with FIGO 2009. METHODS AND MATERIALS: Patients with locally advanced cervical cancer (stage IB2-IVA) who had baseline cross-sectional imaging and received (chemo-) radiation and brachytherapy were included. Survival outcomes were analyzed according to FIGO 2009. Patients were then reclassified according to FIGO 2018, and TNM classification outcomes were analyzed. FIGO stage and known prognostic factors were included in univariate analysis, and multivariate analysis was performed to investigate the prognostic value of clinical stage. RESULTS: Six hundred thirty-two patients were included. Overall, 185 (29.3%) patients had pelvic adenopathy, and 51 (8.2%) had positive paraortic nodes. At a median follow-up of 33 months, 116 (18.3%) patients had recurrence. Three-year disease-free survival (DFS) according to FIGO 2009 for stage IB, IIA, IIB, IIIA, IIIB, and IVA was 86%, 91%, 76%, 57%, 65%, and 61%, respectively. The 3-year DFS after restaging according to FIGO 2018 for stage IB, IIA, IIB, IIIA, IIIB, IIIC1, IIIC2, and IVA was 100%, 93%, 84%, 53%, 77%, 74%, 61%, and 61%, respectively. Patients with clinically significant lymphadenopathy had inferior outcomes compared with node-negative patients (62.9% vs 77.8%; P = .002). Patients with ≥3 paraortic nodes had poorer DFS than patients with <3 paraortic lymphadenopathy (13.6% vs 56.3%; P = .001). Furthermore, patients with primary tumor volume >30 cm3 had worse 3-year DFS than those with primary tumor volume ≤30 cm3 (67.4% vs 78.5%; P = .002). CONCLUSIONS: FIGO 2018 modification is associated with heterogenous outcomes in node-positive patients that are affected by primary tumor and nodal volume. We propose a modification to the existing TNM staging system to allow more robust classification of outcomes.

MRI- and PET-Guided Interstitial Brachytherapy for Postsurgical Vaginal Recurrences of Cervical Cancer: Results of Phase II Study.

PURPOSE: This phase II study evaluated the utility of magnetic resonance imaging (MRI) and positron emission tomography for planning radiation and brachytherapy in patients with postsurgical recurrence of cervical cancer. METHODS AND MATERIALS: The study (NCT01391065) recruited patients with residual or recurrent disease after hysterectomy. Patients underwent baseline T2 weighted (T2W) MRI, 18F-flouro-deoxyglucose (18F-FDG), 18F-flouro thymidine (18F-FLT) and 18F-flouromisonidazole (18F-F Miso) positron emission tomography (PET) and received external radiation (50 Gy/25 fractions for 5 weeks) and weekly cisplatin (40 mg/m2). MRI was performed at brachytherapy and used for delineation of clinical target volume (CTV). Patients with parametrial disease at baseline received interstitial brachytherapy (16-20 Gy/4-5 fractions) and those with vaginal disease received intracavitary brachytherapy (12-14 Gy/2-4 fractions). Kaplan-Meier analysis was performed to evaluate locoregional relapse, disease free survival, and overall survival. Common Toxicity Criteria for adverse event reporting (CTCAE) v4.1 was used for toxicity scoring and European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questtionaire Core 30 (QLQC-30) and Cx 24 for quality-of-life reporting. RESULTS: Between January 2011 and February 2016, 60 patients were included, of which 50 received study treatment. The mean gross tumor volume on T2 W MR was 20 (IQR 3.6-90) cc. The metabolic tumor volume was 15 (interquartile range [IQR] 2.1-56.1) cc. The median FLT volume was 10 (IQR 0-48) cc. A total of 8 patients had 18-F F Miso uptake. The median CTV at brachytherapy was 38 (12-85) cc. The median CTVD90 and D 98 was 71 (53-74) and 74 (53-74) Gy. At a median follow-up of 60 (5-93) months, the 5-year local control, disease free survival, and overall survival were 84%, 73%, and 74.5%, respectively. Grade III and IV proctitis and cystitis were observed in 4% and 2% of patients. On multivariate analysis baseline tumor volume, on T2 W MR impacted disease free (91% vs 65%, P = .03) and overall survival (96% vs 77%, P = .06). CONCLUSIONS: Image-guided assisted radiation and brachytherapy are associated with good to excellent local control and survival in patients with vaginal recurrences of cervical cancer.