Gy In Single Fraction Research Articles

Effects of ionizing radiation in the diagnostic and therapeutic range on the biophysical properties of collagen fibrils.

<h3>Background</h3> Ionizing radiation may indiscriminately and adversely affect tissues during exposure. As collagen is the most abundant protein in the human body, its exposure to ionizing radiation is inevitable. To date, there has been limited comprehensive evaluation of the biophysical properties of individual collagen fibrils exposed to clinically relevant doses of ionizing radiation. <h3>Objective</h3> To assess the effects of ionizing radiation at diagnostic and therapeutic levels on the biophysical properties of collagen at the nanoscale. <h3>Study Design</h3> <i>In vitro</i> acellular type I collagen scaffolds (rat tail origin) were irradiated at two relevant dose levels (diagnostic regime D = 50 µGy and therapeutic regime D = 70 Gy (single fraction)) in hydrated and dehydrated states. Alterations in the biophysical properties of these scaffolds were assessed using atomic force microscopy (AFM) (imaging, nanoindentation) and attenuated total reflectance Fourier-transform infrared (ATR-FTIR) spectroscopy. <h3>Results</h3> Preliminary analysis demonstrated changes in Young's modulus for all samples treated with both diagnostic and therapeutic dose levels, suggesting the presence of internal crosslinking modifications. These hypothesized changes will be further evaluated by fluorescence-lifetime imaging microscopy (FLIM) and dielectric analysis. No changes were detected in the infrared spectrum, suggesting no denaturation of the protein structure. A neural network for texture analysis is in development for AFM image processing and dose correlation quantification. <h3>Conclusion</h3> In this exploratory project, we demonstrated that diagnostic and therapeutic levels of radiation can alter Young's modulus of individual collagen fibers. Evaluation of irradiated collagen changes may prove important in managing oral diseases such as squamous cell carcinoma and radiation-induced mucositis and caries. Additional imaging and image processing studies are ongoing to further characterize the response of collagen to radiation. <b>Statement of Ethical Review</b> Ethical Review or exemption was not warranted for this study

PO-1234 Physical result of Phase II Clinical Trial of 24 Gy Single Fraction SBRT of stage 1-2 breast cancer

PO-1234 Physical result of Phase II Clinical Trial of 24 Gy Single Fraction SBRT of stage 1-2 breast cancer

Primary radiation therapy in stage I/II indolent orbital lymphoma - a comprehensive retrospective recurrence and toxicity analysis.

To provide a comprehensive recurrence and toxicity analysis of patients treated with radiotherapy alone for stage I/II (Ann-Arbor classification) indolent orbital lymphoma. We retrospectively reviewed the medical charts of 46 patients (and 51 orbits) treated at our centre with radiotherapy between 1995 and 2012 for biopsy-proven stage I/IIE primary orbital lymphomas. We evaluated treatment response and performed a comprehensive toxicity analysis with correlation to delivered radiation dose. At diagnosis, the median age was 63.5years (range: 20-92). At initial diagnosis 43 and 3 patients had unilateral, synchronous bilateral involvement while there were 2 cases of contralateral metachronous failure. The predominant histological subtype was extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue in 42 (91.3%), follicular in 1 (2.2%), lymphoplasmacytic lymphoma in 1 (2.2%) and other indolent histology in 2 (4.3%) patients. Most lymphomas were located in the conjunctiva (18/35.3%) or eyelids (18/35.3%). Thirty-eight (82.6%) patients presented with stage I while 8/46 (17.4%) with stage II disease. The median radiation dose was 39.6Gy (range: 21.6-48.6Gy) delivered in 1.8-2Gy single fractions. At a median follow-up of 83months (range: 7-258months), the complete remission rate was 98%. A local relapse was observed in 2/51 (3.9%) orbits and 4/46 (8.7%) patients had systemic relapse. The 5- and 10-year PFS rates were 79.2% (95% CI: 73.0%-85.4%) and 67.6% (95% CI: 59.4%-75.8%); 5- and 10-year OS was 83.6% (95% CI: 77.9%-89.3%) and 76.5% (95% CI: 69.4%-83.6%), respectively. In total, 66 acute toxicity events (all-grade) were observed: 5/51 (9.8%) ≥G2 acute conjunctivitis, 2/51 (3.9%) cases of G2 acute keratitis, 1/51 (2%) cases of ≥G2 ophthalmagia and 12/51 (23.5%) cases of ≥G2 xerophthalmia. Furthermore, 45 chronic adverse events were observed in 34/51 (66.7%) irradiated orbits with 30 late adverse events attributed to cataract. Our analysis confirms the role of radiotherapy alone at lower doses in the treatment of indolent orbital lymphomas. Further research is required to assess the efficacy of ultra-low-dose radiotherapy and anti-CD20 monoclonal antibodies to further mitigate long-term sequelae.

SBRT in Localized Renal Carcinoma: A Review of the Literature.

Stereotactic body radiotherapy (SBRT) allows high doses of radiation to be administered in a limited number of fractions. The high doses per session might allow the theoretical radioresistance of renal carcinoma to be overcome. SBRT may be a therapeutic alternative in inoperable patients with localized renal carcinoma. This review studied the available literature on the use of SBRT in inoperable localized renal carcinoma. The review including data from English-language studies was conducted in PubMed and MEDLINE between January 2010 and December 2020. Articles were included with data from patients with renal carcinoma treated with SBRT, their indications, simulation, dose and fractionation, local control, survival and side effects, comparison with other treatments, response assessment and radioimmunotherapy. The articles included were evaluated for content and validation. The immobilization systems were variable between studies. Doses and fractions were variable from 25-26 Gy in single fractions to 21-48 Gy in 3-5 fractions, with local control being around 90% with a low rate of side-effects. We review the state of the art in SBRT for renal cell carcinoma. More research is needed to determine optimal doses and fractionation, and to develop a reliable response assessment tool. The role of radioimmunotherapy in renal carcinoma is being studied.

An Evaluation of Pain Response Between Single Fraction Radiotherapy Versus 10 Fractions RT in Metastatic Vertebral Bone Disease: A Quasi Experimental Study

The prognosis of bone metastasis is poor, with median survival measured in months, not years. Treatment remains an important issue to alleviate the complications and sufferings of the patients. This study was aimed to evaluate the pain response between single versus multiple fraction radiotherapy in metastatic vertebral bone disease. In this prospective quasi experimental study, the sample consisted of 60 patients of Oncology Dept., KYAMCH. Purposive sampling method was used. The respondents were divided into 2 arms, Arm A consisted of 30 patients, receiving 800 cGy single fraction RT, and Arm B consisted 30 patients who received 3000 cGy multiple fractions RT. The data were collected using a semi-structured questionnaire, which was constructed in line with the reviewed literature along with RECIST (Response Evaluation in Solid Tumor) criteria, VAS (Visual Analogue Scale) after 4 weeks of RT completion and Radiation Therapy Oncology Group (RTOG) criteria. Mean age of Arm A was 43.73 years, and Arm B was 46.8 years. Lung cancer was the leading cancer in both arms, 43.3% and 36.6% respectively. Adenocarcinoma was the commonest histopathological type of cancer found in both arms, 39.9% and 36.6% respectively. To determine associations, Chi-Square tests were done. For Arm A, 66.6% initially presented with severe pain, 23.31% with moderate and 10% with mild pain. In arm B 59.94%, 33.3% and 6.66% patients presented with severe, moderate and mild pain respectively. One month after completion of RT, pain significantly reduced in patients of both arms with a p value of < .001. No significant difference was observed between 8 Gy in single fraction versus 30 Gy in 10 fractions radiotherapy in the management of secondary bone tumour. It was found, both the radiation fractionation schedule for the management of secondary bone tumour are equally effective. More patients can be provided with the desired treatment with shorter period of time. It will certainly ease the economic burden on the patients as well as on the country.

Early Follow-Up of Multi-Institutional Trial of Phase I Dose Escalation Using Single Fraction Stereotactic Partial Breast Irradiation (S-PBI) for Early-Stage Breast Cancer

We report on our early experience of a phase I dose escalation study of single fraction stereotactic partial breast irradiation (S-PBI) for early-stage breast cancer after partial mastectomy using a robotic stereotactic radiation system.Patient eligibility included DCIS or invasive epithelial histologies, AJCC clinical stage 0, I, or II with tumor size < 3 cm, and negative margins. Prior to simulation, 3-4 gold fiducials were placed around the lumpectomy cavity to be used for real-time tracking during treatments. Dose limiting toxicity (DLT) was defined as grade ≥ 3 toxicity by CTCAE (version 4) deemed definitely related to treatment for: skin, ribs/bone (fracture), pulmonary (radiation pneumonitis), or neurological (intercostal or brachial plexus nerves) or any grade 4 or 5 toxicity definitely attributed to therapy. Both patients and physicians completed baseline and subsequent cosmesis outcome questionnaires using a 4-point scale ranging from excellent, good, fair, or poor. Cohort 1 was 22.5 Gy, cohort 2 26.5 Gy, and cohort 3 30 Gy all delivered in a single fraction. Dose escalation was permitted provided that one or fewer of the first seven, or two or fewer of nine patients experienced a DLT within 90 days of treatment within each dose group. If more patients had DLT in a given dose cohort, the maximum tolerable dose (MTD) would have been exceeded.From 4/2016 to 1/2021, 11, 9, and 10 patients were treated on cohorts 1, 2 and 3 respectively. Of these, data from 18 evaluable patients from cohorts 1 and 2 and 6 patients from cohort 3, with at least 12 months of follow up are reported. Median f/u for cohort 1 was 36 m (r 24-48m), cohort 2 was 18 m (r 18-24m), and cohort 3 12 m (r 1-18m). Average age was 66.8 (r 47-84). Histology included 11 DCIS, and 19 invasive carcinomas. Of 11 DCIS, 9 were ER+, and 2 were ER-. All 19 invasive tumors were ER+. 23/29 patients received endocrine therapy, and no patient received chemotherapy. No patients experienced grade 3 or higher treatment related toxicity in the acute period (≤ 90 days), and MTD was not reached. There were two delayed grade 3 toxicities, (dose cohort 1 and 2, one patient had breast pain, and another had mastitis at 12 months and 9 months). No patients experienced grade 4 or 5 toxic events. Five patients developed fat necrosis in all three cohorts. Physicians scored cosmesis excellent or good at last follow-up in (10/11) 90%, (7/8) 87.5%, and (6/6)100%, in cohort 1,2, and 3 respectively, while patients scored excellent or good in (11/11) 100%, 8/8 (100%), and 5/6 (83%) patients. There has been no report of disease recurrences.Dose was escalated to 30 Gy in single fraction, and the majority of patients maintained good or excellent cosmetic outcome, without grade 3 or 4 toxicity. Continued analysis of all cohorts are in progress.

“Big Boom” Radiation Treatment (RT) of 4 Gy Single Fraction: Is It an Acceptable Alternative to “Boom Boom” Radiation Treatment 2 Gyx2 Fractions for Non-Hodgkin Lymphomas (NHL)?

RT plays an important role in the treatment of NHL. Early in the COVID-19 pandemic, in order to decrease patient and staff exposure to potential infection, the International Lymphoma Radiation Oncology Group [ILROG] published emergency guidelines to support hypofractionation across multiple dose regimens. For NHL, ILROG recommended substitution of the familiar 2 Gy x2 regimen with a 4 Gy x1 alternative. This preliminary report describes our center's experience with a regimen of a single dose of 4 Gy ("Big Boom").We present our initial findings of patients treated with 4 Gy x1 between March 30, 2020 through November 30, 2020 (n = 40 lesions; 36 patients). We utilized Lugano PET criteria and clinical assessments to determine patient outcomes. Outcomes included initial clinical/radiographic response and acute toxicities. Patients were treated with either a definitive (curative) or a palliative intent (to relieve symptoms and not necessarily to achieve long-term disease control).Table 1 summarizes the patient and treatment characteristics. 29 patients (72%) were treated with a definitive intent, and 11 (28%) with a palliative intent. Median time to initial assessment for all sites was 2.2 months (range: 0.6-4.4), with overall median follow up time of 3.8 months (range: 1.0-7.3). The overall initial response rate was 85% for all sites, with 59% achieving complete response (CR) and 26% achieving a partial response (PR) (n = 39 lesion sites; 35 patients - 1 patient deceased shortly after RT [unrelated to radiation]). 4 initial partial response/no response (PR/NR) sites later became CR with either additional full dose RT (2 Gyx12) or no other treatments. The median follow-up time for those 4 lesions sites was 4.2 months (range: 2.3-9.2). 9 patients reported grade 1 toxicity, and none had grade 2+ toxicity.Given the initial high response rate and the ease of using a "one and done" treatment method, we propose that the early response rates of using a 4 Gyx1 regimen are similar to that of 4 Gy in 2 fractions. Longer term follow-up is required to confirm the durability of these results. As we continue to accrue and evaluate, data will be updated at the time of the meeting and potentially joined with other centers participating in the comprehensive ILROG-COVID guidelines research effort.

Does Brachytherapy Boost Improve Biochemical Control in Intermediate and High-Risk Prostate Cancer Patients Compared to External Beam Radiotherapy Alone?

<h3>Purpose/Objective(s)</h3> The purpose of this analysis was to investigate whether the combination of external beam radiotherapy (EBRT) and brachytherapy boost (EBRT+BT) is superior to EBRT alone in terms of biochemical control (BC) in the management of intermediate (IR) and high risk (HR) prostate cancer (PC) patients and whether the difference is associated with local biologically effective dose (BED) escalation. <h3>Materials/Methods</h3> We investigated 1123 patients treated for IR (24.8%) or HR PC (75.2%) with EBRT (90.7%) or EBRT+BT (9.3%) at one institution between 2003 and 2012. Kaplan-Meier curves were used to calculate biochemical control. Log-rank testing and Cox regression were used to compare results between groups. BED was calculated using α/β of 3 for PC. The majority of patients treated with EBRT received 76 Gy in 2 Gy fractions (79%, median BED = 126.7 Gy) or equivalent. The majority of patients treated with EBRT+BT received either 54 Gy in 2 Gy fractions followed by 10-11 Gy single fraction BT boost (47.6%, median BED = 133.3 Gy), or 46-50 Gy in 2 Gy fx followed by 20-21 Gy two fraction BT boost (51.4%, median BED = 171.2 Gy). <h3>Results</h3> The median age of the patients was 68-years. The 5-year BC was 79%. There was no statistically significant difference in BC between patients treated with EBRT or BT in IR (<i>P</i> = 0.74) and HR (<i>P</i> = 0.73) PC groups. There was a significant difference between patients receiving lower and higher BED (> 135 Gy) fractionation schemes in favor of higher BED, both for IR (5-y BC of 100% vs 81%, <i>P</i> = 0.02) and HR group (5-y BC of 92% vs 77%, <i>P</i> = 0.02). The BED was inversely associated with risk of BC in univariate analysis (HR = 0.98; CI95% 0.97-0.99; <i>P</i> < 0.01), and remained an independent prognostic factor in the multivariate analysis (HR = 0.97; CI95% 0.96-0.99; <i>P</i> < 0.01) along with Gleason Grade Groups score (HR = 1.18; CI95% 1.05-1.32; <i>P</i> < 0.01). <h3>Conclusion</h3> The combination of EBRT and BT boost has the potential to significantly improve biochemical control in IR and HR prostate cancer patients through local BED escalation. The improvement in BC was observed in patients receiving higher BED, as well as a significant association between BED and risk of biochemical failure.

Proton and Photon Dosimetry of Carbon Fiber-PEEK Implants for Paraspinal Stereotactic Body Radiation Therapy

<h3>Purpose/Objective(s)</h3> Carbon fiber composite (CFR-PEEK) implants have been shown to improve image quality in volumetric imaging compared with titanium (Ti). We perform a dosimetric comparison of proton and photon SBRT plans with Ti and CFR-PEEK implants for paraspinal SBRT treatments. <h3>Materials/Methods</h3> CT scans of a spine phantom embedded with CFR-PEEK and Ti implants were obtained. PTV and OAR contours for a 24 Gy single fraction plan were generated with d_max spinal cord < 14 Gy. Nine-field IMRT photon plans were optimized on both scans. Three-field pencil beam scanning (PBS) plans using multi-field optimization (MFO) were generated. Robust evaluation for 2 mm setup, ± 3.5% range and ± 10% material density override uncertainties were performed. To evaluate the MR image quality of the carbon fiber implants, an implant set was placed in a water phantom. Spine MRI imaging sequences were acquired at 1.5T and 3T and associated artifacts were evaluated. <h3>Results</h3> Target V95 coverage statistics for all plans are shown in Table 1. Photon plans with CFR-PEEK vs. Ti implants were not significantly different. Target coverage goals and OAR constraints were met. When the CFR-PEEK optimized photon plan was recalculated on Ti CT, PTV V100% was reduced by 12.4%, demonstrating the dose perturbation induced by Ti implants. The MFO proton plans for both implant scenarios had lower coverage than the IMRT plans due to the sharper gradients on the IMRT plans. The PBS plan for CFR-PEEK had slightly better coverage than for Ti. Cord-constraint-free proton plans were generated to investigate how the cord constraint impacted the proton plan. Without the constraint, PTV V95% was 99.0% for CFR-PEEK and 94.9% for Ti plans. The increased coverage for CFR-PEEK plan suggests that the potential advantage of CFR-PEEK is masked by the tight cord constraints. In robustness analysis, no clear benefit was shown for range and setup uncertainties. However, advantage in target coverage robustness was seen under material density perturbation analysis. Specifically, the perturbed PTV V95% ranged from 88.7% to 88.4%. In contrast, for Ti plan, PTV V95% varied from 86.5% to 82.3% in perturbed scenarios. In MRI studies, no metal signal loss image artifacts were observed around the CFR-PEEK screws at either field strengths. Minor signal pile-up artifacts of < 5 mm can be seen on one side of the screw in high field 3 T studies but were negligible in 1.5 T studies. <h3>Conclusion</h3> For paraspinal SBRT, utilizing CFR-PEEK compared to Ti implants do not significantly affect plan quality for both PBS and IMRT. Proton plans are more robust for material composition uncertainties only. The largest advantage of CFR-PEEK vs. Ti will be in MR image quality improvements, which can translate to more accurate target delineations and improved follow-up image quality.

PO41: 21 Gy Single Fraction High Dose Rate Brachytherapy for Early Stage Prostate Cancer: Early Outcomes from a Single Institution Prospective Clinical Trial

PO41: 21 Gy Single Fraction High Dose Rate Brachytherapy for Early Stage Prostate Cancer: Early Outcomes from a Single Institution Prospective Clinical Trial

PO41: 21 Gy Single Fraction High Dose Rate Brachytherapy for Early Stage Prostate Cancer: Early Outcomes from a Single Institution Prospective Clinical Trial

Purpose: Previous reports investigating single fraction high dose rate (HDR) brachytherapy as monotherapy for localized prostate cancer have reported favorable toxicity profiles but higher than expected local failure rates. This analysis reports outcomes of a series of patients treated with single fraction HDR brachytherapy to an escalated whole gland dose of 21 Gy.

Outcomes of Palliative Radiotherapy in Metastatic Epidural Spinal Cord Compression in Lung Cancer-A Prospective Observational Study from Tata Memorial Hospital.

Background Metastatic epidural spinal cord compression (MESCC) secondary to lung cancer (LC) is a debilitating complication associated with poor prognosis and is commonly treated with radiotherapy (RT). There is no consensus for RT dose fractionation in spinal cord compression. Methods Forty consecutive patients of LC with radiological evidence of MESCC treated with palliative RT were evaluated for functional outcomes (pain, ambulation, and sphincter function) at 2-, 4-, and 24-week post RT completion. Pain assessment was done using visual analogue scale (VAS) and response was categorized according to international consensus criteria, ambulation status (AS) using Tomita’s scale, and sphincter function by the presence or absence of a catheter. Overall survival (OS) was assessed using Kaplan-Meier method and compared using log-rank test. Impact of potential prognostic factors on survival was also analyzed and p -value ≤0.05 was considered significant. Results Sixteen, 22, and two patients received 8 Gy single fraction (SF), 20 Gy in five fractions (20/5), and 30 Gy in 10 fractions (30/10), respectively. At 2 weeks, overall response (OR) rates of pain, ambulation, and sphincter control were 73, 81, and 81%, respectively. At 4 and 24 weeks, 93.7, 84.3, 87.5% and 88, 94, 76.5% had OR, respectively. Median OS was 4 months. Six- and 12-months OS was 50 and 37.5%. Nonsignificant difference in OS was seen between SF and 20/5 fractions (median 2.2 vs. 7.1 months, p = 0.39). Age ≤50 years was the only significant factor ( p <0.05) in univariate analysis for OS. Conclusion Radiotherapy provided equivalent pain control, ambulation, and sphincter function compared with reported literature in MESCC. Nonsignificant difference in OS exists between SF and multifraction RT regimens.

Single dose high-dose-rate brachytherapy with focal dose escalation for prostate cancer: Mature results of a phase 2 clinical trial

AimThe dominant intraprostatic lesion (DIL) is the commonest site of relapse after single dose high-dose-rate brachytherapy (HDR-BT) for localised prostate cancer. This study investigated toxicity and clinical outcomes of focal dose escalation to the DIL with dose de-escalation to the remaining prostate. Materials/MethodsBetween November 2012 and July 2016, 50 patients with localised prostate adenocarcinoma received single fraction HDR-BT. 21 Gy was prescribed to the DIL, with two de-escalation prescription schedules for the remaining prostate. Primary outcomes included biochemical no evidence of disease (bNED), local recurrence free survival (LRFS), and metastasis free survival (MFS). Secondary outcomes included late genitourinary, gastrointestinal and sexual toxicity. Kaplan—Meier analyses with log rank tests were used to estimate bNED, LRFS and MFS. ResultsWith a median follow up of 70.6 months, 15 patients developed biochemical failure, including 8 in the group that received minor dose de-escalation to the non-DIL prostate (group 1) and 7 in the group that received moderate de-escalation (group 2). Five-year bNED was 88% in group 1 and 76% in group 2 (p = 0.05). Overall 4-year and 5-year FFLF in group 1 was 100% and 96% and in group 2 92% and 84%. These differences were statistically significant (p = 0.03). No acute ≥G3 genitourinary or ≥G2 gastrointestinal toxicity was reported. The median IIEF decreased in the first 6 months improving to a peak median score of 20 at 54 months. ConclusionFocal boost to the DIL did not improve biochemical or local control after single-fraction HDR monotherapy compared to what would be expected from 19 Gy single fraction treatment to the whole gland.

Fever range whole body hyperthermia for re-irradiation of head and neck squamous cell carcinomas: Final results of a prospective study

ObjectivesFever-range whole body hyperthermia (FRWBH) has been shown to improve tumor oxygenation in vivo. A prospective pilot study addressed the question if addition of FRWBH to re-irradiation is feasible in recurrent head and neck squamous cell carcinomas (HNSCC) with unfavorable prognostic features. Materials and methodsThe study completed accrual with the recruitment of ten patients between April 2018 and March 2020. Re-irradiation was administered using volumetric arc hyperfractionated radiotherapy with bi-daily 1.2 Gray (Gy) single fractions and a total dose of 66 Gy to all macroscopic tumor lesions. Concomitant chemotherapy consisted mostly of cisplatin (7 patients). FRWBH was scheduled weekly during re-irradiation. The study was registered in the clinicaltrials.gov database (NCT03547388). ResultsOnly five patients received all cycles of FRWBH. Poor patient compliance, active infections during treatment and study restrictions due to the Covid-19 pandemic were the main reasons for omitting FRWBH. No increase of acute toxicity was observed by FRWBH. Exploratory evaluation of outcome data suggests that FRWBH treatment according to protocol does not seem to have a detrimental effect on tumor control or survival and might even increase treatment efficacy. ConclusionFRWBH is difficult to apply concomitant to re-irradiation in HNSCC. No excess toxicity was observed in patients receiving FRWBH and exploratory analyses suggest potential anti-tumor activity and decreased patient-reported depression scores after FRWBH.

Palliative radiotherapy for bladder cancer: a systematic review and meta-analysis

Background/Purpose The optimal dose fractionation for palliative radiotherapy (RT) in patients with symptomatic advanced bladder cancer is unclear. This study aimed to determine if a higher dose of RT was associated with improved symptoms response rates. Methods We searched PubMed, Central and Embase for eligible studies published from 1990 to 2019. The primary outcomes were symptoms response rates for hematuria, dysuria and frequency. Secondary outcomes included treatment-related adverse events and quality of life. Results We found one randomized, four prospective and eight retrospective non-comparative observational studies including 1320 patients who received palliative bladder radiotherapy for symptom relief. The dose fractionation schedules varied across studies ranging from 8 Gy single fraction to 60 Gy in 2 to 8 Gy per fraction. The pooled response rates for hematuria, dyuria and frequency symptoms were 74%, 58% and 71% respectively. A higher dose of RT was not associated with improved response rates of hematuria and frequency. However, a higher dose of RT was associated with a longer duration of hematuria response and reduced response of dysuria. Grade 3 gastrointestinal and genitourinary toxicity occurred in up to 26% of patients. Health-related quality of life (HRQOL) outcomes were reported in one study. Conclusion This systematic review demonstrates that a higher dose of bladder RT was not associated with improved response rates of hematuria and frequency symptoms but was associated with reduced response of dysuria. Higher doses of bladder RT was associated with more durable hematuria response. Prospective studies to determine the effects of palliative bladder radiotherapy on HRQOL outcomes are warranted

ROAD: ROtational direct Aperture optimization with a Decoupled ring-collimator for FLASH radiotherapy

Ultra-high dose rate in radiotherapy (FLASH) has been shown to increase the therapeutic index with markedly reduced normal tissue toxicity and the same or better tumor cell killing. The challenge to achieve FLASH using x-rays, besides developing a high output linac, is to intensity-modulate the high-dose-rate x-rays so that the biological gain is not offset by the lack of physical dose conformity. In this study, we develop the ROtational direct Aperture optimization with a Decoupled ring-collimator (ROAD) to achieve simultaneous ultrafast delivery and complex dose modulation. The ROAD design includes a fast-rotating slip-ring linac and a decoupled collimator-ring with 75 pre-shaped multi-leaf-collimator (MLC) modules. The ring-source rotates at 1 rotation per second (rps) clockwise while the ring-collimator is either static or rotating at 1 rps counterclockwise, achieving 75 (ROAD-75) or 150 (ROAD-150) equal-angular beams for one full arc. The Direct Aperture Optimization (DAO) for ROAD was formulated to include a least-square dose fidelity, an anisotropic total variation term, and a single segment term. The FLASH dose (FD) and FLASH biological equivalent dose (FBED) were computed voxelwise, with the latter using a spatiotemporal model accounting for radiolytic oxygen depletion. ROAD was compared with clinical volumetric modulated arc therapy (VMAT) on a brain, a lung, a prostate, and a head and neck cancer patient. The mean dose rate of ROAD-75 and ROAD-150 are 76.2 Gy s−1 and 112 Gy s−1 respectively to deliver 25 Gy single-fraction dose in 1 s. With improved PTV homogeneity, ROAD-150 reduced (max, mean) OAR physical dose by (4.8 Gy, 6.3 Gy). The average R50 and integral dose of (VMAT, ROAD-75, ROAD-150) are (4.8, 3.2, 3.2) and (89, 57, 56) Gy×Liter, respectively. The FD and FBED showed model dependent FLASH effects. The novel ROAD design achieves ultrafast dose delivery and improves physical dosimetry compared with clinical VMAT, providing a potentially viable engineering solution for x-ray FLASH radiotherapy.

Dosimetry of local failure with single dose 19 Gy high-dose-rate brachytherapy for prostate cancer

Purpose/objectiveLong-term follow up of single dose high-dose rate brachytherapy (HDR BT) for localised prostate cancer has revealed higher than expected rates of biochemical and local failure. This study aimed (i) to investigate the pattern of relapse within the prostate with reference to the initial site of disease in those patients; and (ii) to examine if there were any relationships between the HDR BT dosimetric parameters to these areas of recurrence. Materials/methodsA retrospective review of treatment records of patients who received 19 Gy single fraction of HDR BT was carried out. A matched pair analysis used one control for each biochemical recurrence case matched with pre-treatment Clinical target volume (CTV) size, Gleason score, T stage, risk category and presence of an identifiable dominant intraprostatic nodule (DIL) for each biochemical recurrence case identified.For all datasets, the pre HDR BT DILs were delineated on the diagnostic pre-treatment T2-weighted MRI and planning CT images. For patients with local recurrence post HDR BT, the recurrent nodules were contoured on the diagnostic T2-weighted MRI and choline PET which were registered to the original HDR BT planning CT.Dosimetric parameters of CTV, planning target volume (PTV), DIL and organs at risk (OARs) were evaluated. Wilcoxon signed-rank test was performed to investigate if there were any significant differences in dosimetric parameters between cases and controls. Cox regression analysis was performed to explore if there were any clinical and dosimetric parameters predicting for biochemical progression free survival (bPFS), local recurrence free survival (LR-PFS) and DIL recurrence free survival (DIL-PFS). ResultsBetween 2013 and 2018, 180 patients received 19 Gy HDR-BT monotherapy. With a median follow up of 36 months, 19 (10.6%) patients developed biochemical recurrence. Of the 19 patients with biochemical failure, 13 had a local recurrence, including 7 who occurred at the site of DIL.Thirty-eight intermediate/high risk patients were included in the matched pair analysis. No statistically significant differences were found in all CTV, PTV, DIL and OAR dosimetric parameters between cases and controls (p > 0.05).For the Cox regression analysis, none of the covariates investigated were found to be statistically significant factors to predict for bPFS, LC-PFS and DIL-PFS. ConclusionNo associations between biochemical recurrences and HDR BT dosimetry were identified in our cohort of patients receiving 19 Gy single fraction HDR BT. A large proportion of recurrences occurred at the site of original disease. HDR BT for intermediate/high risk prostate cancer should be undertaken using a minimum of two fractions.

Therapeutic outcomes of nasopharyngeal carcinomas: a single-center study conducted at the Fattouma Bourguiba University Hospital in Monastir, Tunisia

Introductionles carcinomes nasopharyngés (CNP) sont relativement fréquents dans le pourtour méditerranéen. La survie a été largement améliorée avec les nouvelles techniques d´irradiation et les nouvelles molécules de chimiothérapie. L´objectif de notre étude est d´analyser les résultats thérapeutiques et décrire les facteurs pronostiques des CNP.Méthodesil s´agit d´une étude rétrospective menée entre janvier 1995 et décembre 2014, des observations de patients traités et suivis dans notre service pour un carcinome du nasopharynx. Le recueil des données a été réalisé à partir d´une fiche type. L´analyse statistique a été réalisée à l´aide du logiciel SPSS. La survie a été calculée selon la méthode de Kaplan-Meier.Résultatssoixante-treize cas de CNP ont été colligés. L´âge moyen était de 48 ans. Une prédominance masculine a été notée. La majorité des tumeurs (56%) étaient localement avancées (T3-T4). Après un recul moyen de 45,5 mois, le taux de récidives locorégionales était de 19,4%. Trois patients (4%) ont présenté des métastases osseuses. La survie globale à 5 ans était de 65%. Les facteurs influençant positivement la survie globale à l´analyse étaient le stade TNM précoce et le fractionnement de 1,8 Grays/séance de la radiothérapie. Les taux de récidives locales et ganglionnaires étaient respectivement de 13,8% et 5,5%, essentiellement pour des tumeurs classées T4 N2. Les séquelles thérapeutiques étaient dominées par les otites séromuqueuses (42,7%), le trismus (38,7%) et la xérostomie (32%).Conclusionla survie globale des CNP s´est améliorée particulièrement avec l´avènement de la radio-chimiothérapie concomitante. Néanmoins, la toxicité tardive invalidante demeure non négligeable. Les facteurs de bon pronostic retrouvés dans cette étude étaient le stade tumoral précoce ainsi que la modalité de fractionnement de la radiothérapie.

Tumor Control Probability of Radiosurgery and Fractionated Stereotactic Radiosurgery for Brain Metastases

As part of the American Association of Physicists in Medicine Working Group on Stereotactic Body Radiotherapy, tumor control probability (TCP) after stereotactic radiosurgery (SRS) and fractionated stereotactic radiosurgery (fSRS) for brain metastases was modeled based on pooled dosimetric and clinical data from published English-language literature. PubMed-indexed studies published between January 1995 and September 2017 were used to evaluate dosimetric and clinical predictors of TCP after SRS or fSRS for brain metastases. Eligible studies had ≥10 patients and included detailed dose-fractionation data with corresponding ≥1-year local control (LC) data, typically evaluated as a >20% increase in diameter of the targeted lesion using the pre-SRS diameter as a reference. Of 2951 potentially eligible manuscripts, 56 included sufficient dose-volume data for analyses. Accepting that necrosis and pseudoprogression can complicate the assessment of LC, for tumors ≤20 mm, single-fraction doses of 18 and 24 Gy corresponded with >85% and 95% 1-year LC rates, respectively. For tumors 21 to 30 mm, an 18 Gy single-fraction dose was associated with 75% LC. For tumors 31 to 40 mm, a 15 Gy single-fraction dose yielded ∼69% LC. For 3- to 5-fraction fSRS using doses in the range of 27 to 35 Gy, 80% 1-year LC has been achieved for tumors of 21 to 40 mm in diameter. TCP for SRS and fSRS are presented. For small lesions ≤20 mm, single doses of ≈18 Gy appear generally associated with excellent rates of LC; for melanoma, higher doses seem warranted. For larger lesions >20 mm, local control rates appear to be ≈ 70% to 75% with usual doses of 15 to 18 Gy, and in this setting, fSRS regimens should be considered. Greater consistency in reporting of dosimetric and LC data is needed to facilitate future pooled analyses. As systemic and biologic therapies evolve, updated analyses will be needed to further assess the necessity, efficacy, and toxicity of SRS and fSRS.

Multi-Institutional Trial of Phase I Dose Escalation Using Single Fraction Stereotactic Partial Breast Irradiation (S-PBI) for Early Stage Breast Cancer

We report on our early experience of a phase I dose escalation study of single fraction stereotactic partial breast irradiation (S-PBI) for early stage breast cancer after partial mastectomy using a robotic stereotactic radiation system. Patient eligibility included DCIS or invasive epithelial histologies, AJCC clinical stage 0, I, or II with tumor size < 3 cm, and negative margins. Prior to simulation, 3-4 gold fiducials were placed around the lumpectomy cavity to be used for real-time tracking during treatments. Dose limiting toxicity (DLT) was defined as grade ≥ 3 toxicity by CTCAE (version 4) deemed definitely related to treatment for: skin, ribs/bone (fracture), pulmonary (radiation pneumonitis), or neurological (intercostal or brachial plexus nerves) or any grade 4 or 5 toxicity definitely attributed to therapy. Both patients and physicians completed baseline and subsequent cosmesis outcome questionnaires using a 4-point scale ranging from excellent, good, fair, or poor. Initial dose cohort was 22.5 Gy delivered in single fraction, and dose cohorts 2 and 3 (26.5 Gy and 30 Gy in single fraction, respectively). Dose escalation was permitted provided that one or fewer of the first seven, or two or fewer of nine patients experienced a DLT within 90 days of treatment within each dose group. If more patients had DLT in a given dose cohort, the maximum tolerable dose (MTD) would have been exceeded. From 4/2016 to 1/2020, 11, 8, and 8 patients were treated on cohorts 1, 2 and 3 respectively. Of these, data from 19 evaluable patients from cohorts 1 and 2 with at least 12 months of follow up are reported. Median f/u for cohort 1 was 27.3 m (r 24-36m), and cohort 2 was 15 m (r 12-18m). Average age was 65 (r 47-84). Histology included 9 DCIS, and 10 invasive carcinomas. Of 9 DCIS, 8 were ER+, and 1 was ER-. All 10 invasive tumors were ER+. 17/19 patients received endocrine therapy, and no patient received chemotherapy. In cohorts 1 and 2, no patients experienced grade 3 or higher treatment related toxicity in the acute period (≤ 90 days), and MTD was not reached. There were two delayed grade 3 toxicities, one in each cohort (one patient had breast pain, and another had mastitis, at 12 months and 9 months). No patients experienced grade 4 or 5 toxic events. Four patients developed fat necrosis diagnosed at 10 and 12 mo. in cohort 1, and 9 and 10 months after radiation treatments (with only 1 being painful and others asymptomatic). Physicians scored cosmesis excellent or good in 100%, 100%, 100%, and 100%, respectively, at baseline, 3, 6, and 12 months post S-PBI, while patients scored the same periods 89.5%, 95%, 100%, and 90.9%. There has been no report of disease recurrences. Dose was escalated to 30 Gy in single fraction without a DLT, and the majority of patients maintained good or excellent cosmetic outcome. Continued analysis of all cohorts is in progress.