3D Conformal Radiotherapy Research Articles

In vivo dose measurements for tangential field-in-field ultra-hypofractionated breast radiotherapy

IntroductionUltra-hypofractionated radiotherapy (UHF-RT) mandates more accuracy in each part of the treatment cycle to maximize cure rates and minimize toxicities. In vivo dosimetry is a direct method for verifying overall treatment accuracy. This study evaluated uncertainties in the delivered dose of Hypofractionated (HF) and UHF Whole Breast Irradiation (WBI) and to analyze the accuracy of the workflow to pave the way for a wide-scale use of UHF-RT. MethodsThirty-three breast cancer cases, including 16 HF-WBI and 17 UHF-WBI were treated with 3D conformal Radiotherapy (3D-CRT), where 79 fields were analyzed for dose verification. The measurement point was set at the beam entrance (1.5 cm depth). The expected dose at Dmax was calculated via TPS. Before in vivo measurements, diode detectors were tested and calibrated. We developed initial validation measurements for UHF-RT on an anthropomorphic breast phantom for the first time. ResultsFor RANDO phantom, the percentage difference between measured and calculated doses showed an average of -0.52 ± 5.4%, in addition to an excellent dose reproducibility within 0.6%. The overall in vivo measurements for studied cases showed that 83.5% of the measured doses were within ±5% and only 1.8% of the measured doses were greater than ±10% of the calculated doses. The percentage accuracy was slightly larger for UHF cohort (84.2%) compared to HF cohort (83.2%). The maximum percentage difference between them was less than 1%. ConclusionBreast in vivo dosimetry is an adequate tool for treatment verification that improves the accuracy of the treatment cycle. UHF-RT may contribute in reducing the long waiting lists, increasing patient convenience, and saving the available resources for breast cancer patients.

Radiation therapy of breast cancer in the Nahe Breast Center: first results of an analysis in the context of health services research.

The first evaluation of radiotherapy results in patients with breast cancer treated as part of amultimodal oncologic therapy in the Nahe Breast Center is presented. Analysis of the results was performed using an in-practice registry. From September 2016 to December 2017, 138 patients (median age 62.5years; range 36-94years) with breast cancer (right side, n = 67; left side, n = 71) received adjuvant radiation therapy. Of these, 103 patients received gyneco-oncologic care at the Nahe Breast Center, and 35were referred from outside breast centers. The distribution into stages was as follows: stageI, n = 48; stageII, n = 68; stageIII, n = 19; stageIV, n = 3. Neoadjuvant chemotherapy was given to 19and adjuvant chemotherapy to 50patients. Endocrine treatment was given to 120 patients. Both 3D conformal (n = 103) and intensity-modulated (n = 35) radiotherapy were performed with amodern linear accelerator. With amedian follow-up of 60months (1-67), local recurrence occurred in 4/138 (2.9%) and distant metastasis in 8/138 (5.8%) patients; 7/138 (5.1%) patients died of their tumors during the follow-up period. The actuarial 5‑year local recurrence-free survival of all patients was 97.1%, and the actuarial 5‑year overall survival of all patients was 94.9%. We observed no grade3 or4 radiogenic side effects. The results of radiotherapy for breast carcinoma at the Nahe Breast Center are comparable to published national and international results. In particular, the local recurrence rates in our study, determined absolutely and actuarially, are excellent, and demonstrate the usefulness of radiotherapy.

A retrospective comparison of setup accuracy from CBCT and SGRT data in breast cancer patients

IntroductionBoth cone-beam computed tomography (CBCT) and surface-guided radiotherapy (SGRT) are used for breast patient positioning verification before treatment delivery. SGRT may reduce treatment time and imaging dose by potentially reduce the number of CBCT needed. The aim of this study was to compare the displacements resulting in positioning from the Image Guided Radiation Therapy (IGRT) 3D and SGRT methods and to design a clinical workflow for SGRT implementation in breast radiotherapy to establish an imaging strategy based on the data obtained. MethodsFor this study 128 breast cancer patients treated with 42.5 Gy in 16 fractions using 3D conformal radiotherapy with free breathing technique were enroled. A total of 366 CBCT images were evaluated for patient setup verification and compared with SGRT. Image registrations between planning CT images and CBCT images were performed in mutual agreement and in online mode by three health professionals. Student's paired t‐test was used to compare the absolute difference in vector shift, measured in mm, for each orthogonal axis (x, y, z) between SGRT and CBCT methods. The multidisciplinary team evaluated a review of the original clinical workflow for SGRT implementation and data about patients treated with the updated workflow were reported. ResultsComparison of the shifts obtained with IGRT and SGRT for each orthogonal axis (for the x-axes the average displacement was 0.9 ± 0.7 mm, y = 1.1 ± 0.8 mm and z = 1.0 ± 0.7 mm) revealed no significant statistical differences (p > 0.05). Using the updated workflow the difference between SGRT and IGRT displacements was <3 mm in 91.4 % of patients with a reduction in total treatment time of approximately 20 %, due to the reduce frequency of the CBCT images acquisition and matching. ConclusionsThis study has shown that IGRT and SGRT agree in positioning patients with breast cancer within a millimetre tolerance. SGRT can be used for patient positioning, with the advantages of reducing radiation exposure and shorter overall treatment time.

281P 10-year treatment outcome of prostate cancer patients with 3D conformal radiation: Experience of a single cancer institution in Iran

281P 10-year treatment outcome of prostate cancer patients with 3D conformal radiation: Experience of a single cancer institution in Iran

Considerations for MR-linac bunker shielding design

Purpose. To show the considerations followed for MR-linac in shielding design for the first MR-linac in Mexico following the national clinical necessities. Method. The National Council on Radiation Protection and Measurements (NCRP) 151 recommendations were followed for the shielding design for primary and secondary barriers and the door design. The calculations were made considering the clinical demands in the country, that is, intensity modulated (IMRT) and 3D conformal radiotherapy (3DC-RT) in 80%–20% proportion. Results. The values obtained in the level survey fully comply with the limits established by the national regulatory authority and with those recommended by the International Commission on Radiological Protection (ICRP) for public and occupational exposures. Conclusion. It is remarkable that the workload may increase or that the doses per patient may increase considering occupancy factors, which would allow the introduction of hypofractionated techniques with the same number of patients considered in this work without the need to make modifications in the bunker design.

Utility of the "All of Us" Database for Radiation Oncology Research.

We provide an overview the All of Us Research Program, a National Institutes of Health funded research database, and report on the utility of this database for Radiation Oncology research. The All of Us Research Program aims to create a large and diverse health database with participants from across the US. Patients consent to join the database and agree to share electronic health records, complete surveys, provide physical measurements, and donate at least one biospecimen. In this observational study, we used the public data browser feature of the All of Us Dataset to evaluate utility for future radiation oncology research. Within the database, we report on the number of cases of common cancers in the US, using ICD10 codes, and also the number of patients treated with common radiotherapy procedures, using CPT4 codes. We then qualitatively report on additional data of interest. Of note, public patient counts in All of Us is rounded to the nearest interval of 20. Additional tiers of data access exist, including individual level data, which were not used in this survey of public data. The database includes 372,380 participants, of which 46,380 patients have a diagnosis of cancer. Within the identified top 10 cancers according to ACS, there were a total of 26,540 primary malignant cancers. The most common type of cancers were breast cancer (ICD10 - c50 [n = 6,960]), Prostate (ICD10 - c61 [n = 4,500]), Non-Hodgkin lymphoma (ICD10 - c85 [n = 2860]), Lung & bronchus (ICD10 - c34 [n = 2000]), Colon (ICD10 - c18 [n = 1940]), Melanoma of the skin (ICD10 - c43 [n = 1740]), Thyroid(ICD10 - c73 [n = 1720]), Kidney (ICD10 - c64 [n = 1300]), Urinary bladder (ICD10 - c67 [n = 1140]). The most common radiation therapy procedures were Computerized Tomography simulation (CPT - 77290 [n = 4,040]), Intensity Modulated Radiation Therapy (CPT - 77386 [n = 780]), 3D conformal radiation therapy (CPT - 77412 [n = 1,720]), Stereotactic Body Radiation Therapy (CPT - 77373 [n = 400]), Brachytherapy (CPT - 77770- 77772 [n = 240]), and Proton Therapy (CPT - 77520-77525 [n = 140]). Qualitatively, other data within All of Us include labs values, drug exposures, comorbidities, other procedures, physical measurements, and wearable biometrics (Fitbit) data. Genomic data typically includes germline testing using whole genome sequencing or genotyping array. Patient surveys include data on personal medical history, family health history, lifestyle, social determinants of health, COVID19 experience, and overall health. Potential outcome variables of interest to oncology research in the database include survival, cause of death, additional procedures or diagnoses after cancer treatment, and quality of life metrics derived from the survey instruments. The All Of Us Research Database includes a large number of cancer cases, of which a substantial number received radiotherapy. Future work will focus on focused hypothesis-driven research questions.

Novel hybrid treatment planning approach for irradiation a pediatric craniospinal axis

This study presents a new treatment planning approach merging 3D-CRT and VMAT fields into a hybrid treatment plan (HybTP), in order to achieve an optimum dose coverage of the planning target volume (PTV) and protection of OAR. Craniospinal axis irradiation (CSI) treated with 3D conformal radiotherapy (3D-CRT) is associated with high doses to the heart and eye lenses but provides better sparing of lungs and kidneys compared to volumetric modulated arc therapy (VMAT). VMAT treatment spares eye lenses and the heart, but lungs and kidneys are not as effective as 3D-CRT. Thus, a combination of both techniques (HybTP) may be optimal in sparing all these organs at risk (OAR). The results of HybTP are compared with helical tomotherapy (HT), intensity modulated radio therapy (IMRT), VMAT, and 3D-CRT plans. Hybrid, HT, VMAT, IMRT, and 3D-CRT treatment plans for a male child (age 6 years) with medulloblastoma were created and compared. A total dose of 35.2 Gy (PTV) with a dose per fraction of 1.6 Gy was prescribed. The following dose acceptance criteria were defined:(1)Mean PTV dose should be 100% of the prescribed dose, while the maximum dose should not exceed 107%.(2)At least 98% of the PTV should receive 95% of the prescribed dose.(3)The cribriform plate should be covered by the 95% isodose line.(4)The acceptance criteria for the OARs were: lenses Dmax<10 Gy, lungs Dmean<7 Gy, kidneys Dmean<15 Gy, heart Dmean<26 Gy, and heart V25<10%.The plans were compared regarding dose homogeneity index (HI) and conformity index (CI), PTV coverage, (particularly at cribriform plate) and doses at OARs. Best conformity was achieved with HT (CI = 0.98) followed by VMAT (CI = 0.96), IMRT (CI = 0.91), HybTP (CI = 0.86), and 3D-CRT (CI = 0.83). The homogeneity index varied marginally. For both HT and IMRT the HI was 0.07, and for 3D-CRT, VMAT and HybTP the HI was between 0.13 and 0.15. The cribriform plate was sufficiently covered by HybTP, VMAT, and 3D-CRT. The dose acceptance criteria for OARs were met by HT and HybTP. VMAT did not meet the criteria for lung (Dmean = right 10.4 Gy/left 10.2 Gy), 3D-CRT did not meet the criteria for eye lenses (Dmax = right 32.3 Gy/left 33.1), and heart (V25≈44%) and IMRT did not meet the criteria for lung (Dmean = right 11.1 Gy/left 11.2 Gy) and eye lenses (Dmax = right 12.2 Gy/left 13.1). HybTP meets all defined acceptance criteria and has proved to be a reasonable alternative for CSI. With HybTP that combines VMAT at the brain and heart with 3D-CRT posterior spinal fields (to spare lungs and kidneys), both appropriate coverage of the PTV and sparing of OAR can be achieved.

Low Dose Involved Site Radiotherapy as Single Modality Treatment for Early-Stage Nodular Lymphocyte Predominant Hodgkin Lymphoma.

Involved site radiotherapy as a single modality is considered standard of care for early-stage non-bulky nodular lymphocyte predominant Hodgkin's Lymphoma (NLPHL) with excellent rates of local control and overall survival. Guidelines suggest a dose of 30 Gy in conventional fractionation, however NLPHL has an indolent course and clinically behaves likes a low-grade lymphoma. Given the good prognosis NLPHL has been treated as low grade non-Hodgkin's lymphoma with a dose of 24 Gy in 12 fractions. Eleven patients with stage I-II non-bulky NLPHL treated with involved site radiotherapy alone to a dose of 24 Gy in 12 fractions between 2010 and 2021 were respectively identified and reviewed. Data on toxicity, post treatment PET, relapse and site of relapse were recorded from multidisciplinary meetings records and regular six monthly clinic reviews. Mean patient age was 45 (range 25-74), 9 were male. 8 were classified as having Ann-Arbor stage IA disease, and the remaining 3 had IIA disease. All patients were prescribed 24 Gy in 12 fractions, 6 patients had 3D-conformal radiotherapy, 1 static IMRT and 4 VMAT. After a median follow up of 32 months (range 12-147) the overall response rate was 100% and all patients had complete metabolic response on PET scan, performed three months following the completion of radiotherapy. All patients remained disease free throughout the follow up period (PFS and OS 100%). There were no late toxicities reported. This is the largest reported series of NLPHL patients treated with low dose involved site modern radiotherapy. Patients had excellent local control rates and survival with no significant toxicity, supporting the use of 24 Gy in early-stage non-bulky disease.

Contouring - How Do We Manage This Pivotal but Time-Consuming Workload?

Advanced radiation treatment planning is a complex, multi-step process beginning with image acquisition and using these images to contour radiation targets and organs at risk prior to radiation treatment planning. Contouring is a time-consuming process. Unfortunately, few radiation oncologists have dedicated contouring time allocated in their daily schedule. Also, across radiation practices there is variability amongst dosimetrists, physicists, and physicians in the assignment of contouring responsibilities. The goal of this survey was to explore how the multi-disciplinary task of contouring for treatment planning is managed across radiation oncology practices and its impact on quality of life (QOL) amongst dosimetrists, physicists, and physicians. A comprehensive 19-question Qualtrics survey was created evaluating all aspects of contouring and radiation treatment planning and its impact on QOL. The survey was distributed through Twitter, AAMD, a Medical Physics Journal, as well as directly to radiation oncology practices. Survey responses were summarized as proportions and associations tested using Fisher's exact test. Physicians spent more time completing job responsibilities after work than dosimetrists and physicists, with an average of 6.22 hours (range 0-20) in comparison to 4.16 (0-30) for dosimetrists and 1.55 (0-12) for physicists (p-value 0.001). Physicians on average spent more time contouring on weekends with 1.81 hours (0-10) in comparison to 0.54 (0-10+) for dosimetrists and 0.31 (0-10) for physicists (p-value <0.001). When considering QOL and time spent after work, more respondents agreed there was a negative impact on QOL with increased responsibilities outside work hours (p-value <0.001). On average, respondents performed anywhere from 0 to 85 weekly radiotherapy simulations. The average time delay between simulation and when the imaging datasets are ready for contours was 1.31 days (1-4). 84 respondents signified there is no repercussion for delayed contour plans as planning is fast-tracked to meet the deadline, while 52 respondents signified postponement of radiotherapy start date. Time spent contouring after work hours (p-value 0.148) and on the weekend (p-value 0.403) were similar for both academic and private centers. Similarly, there was no difference in time of days of completion of 3D Conformal Radiation Therapy (p-value 0.551), Intensity Modulated Radiation Therapy (p-value 0.222), or Stereotactic Body Radiation Therapy (p-value 0.551) from academic versus private centers. We present new insight into the amount of time spent in radiation oncology practices by dosimetrists, physicists, and physicians, performing the critical task of contouring for radiation treatment planning and its impact on QOL. These results can be used to guide decisions in the clinic for allocation of radiation treatment planning time and manpower.

Comparison of Hybrid Techniques with 3D-Conformal Radiotherapy in Patients with Lung Cancer

Purpose: It’s postulated that hybrid techniques (HT) with lower weighting of IMRT/VMAT component would improve lung dose-volume parameters despite some disadvantage in PTV homogeneity index (HI) and target coverage (TC). &#x0D; Material and Methods: Conformal plans were prepared using 6-10-15 MV-X photon energies while IMRT/VMAT plans of HTs were prepared using 6MV-X. Four HTs were developed having two different ratios (10% and 50%) of IMRT/VMAT component (h-IMRT1, h-IMRT2 and h-VMAT1, h-VMAT2, respectively). HTs were compared with 3D-CRT in terms of HI and TC for PTV, and total lung (TL) and contralateral lung (CL) V5Gy, V10Gy, V20Gy and mean lung dose (MLD). &#x0D; Results: All HTs were advantageous for HI and TC, while disadvantageous for TL and CL-V5Gy. H-IMRT2 provided better TC than h-IMRT1, and so did h-VMAT2 compared to h-VMAT1. Lower weighting of IMRT/VMAT decreased TL and CL-V5Gy in HTs. In addition, h-IMRT1 decreased TL and CL-MLD and CL-V20Gy compared to h-IMRT2, while h-VMAT2 decreased TL-V20Gy and CL-MLD compared to h-VMAT2. &#x0D; Conclusion: In the RT of lung tumors close to vertebra, it may be appropriate to suggest a ratio of IMRT/VMAT component about 10% in order to decrease the low and intermediate dose-wash lung volume, if HI and TC values are acceptable.

Association of Provider Zip Code Sociodemographic Characteristics with Radiation Therapy Modality Use in the Medicare Population

Variations in healthcare delivery by provider and patient-level characteristics have been well studied in the US health system as a whole, though these patterns are not as well defined in radiation oncology. We evaluated the association of provider zip-code level sociodemographic characteristics with variations in radiation therapy (RT) modality use. We used the Centers for Medicare & Medicaid Services (CMS) Physician and Other Supplier Public Use File, CMS Physician Compare, and National Neighborhood Data Archive databases to link non-facility based radiation oncologists and their submitted Medicare charges in 2020 with sociodemographic information of the provider's zip code. We selected radiation oncologists who submitted for any of the following RT treatments: proton RT (PRT), stereotactic body RT (SBRT), intensity modulated RT (IMRT), 3D conformal RT (3DCRT), and brachytherapy (BT). Sociodemographic covariates included predominant race/ethnicity of area (Black, White, or Hispanic), percentage of population earning above $75,000 annually, provider rurality (metropolitan vs non-metropolitan), and predominant education level attained of area (Bachelor's degree vs no Bachelor's degree). We measured the association of these covariates with the use of different RT modalities with multivariable logistic regression. We identified 1,126 radiation oncologists for analysis. PRT was more likely to be used by providers in areas with a predominantly Black population compared with providers in areas with a predominantly White or Hispanic population (Black as reference, White odds ratio (OR) 0.11; 95% CI 0.05-0.24; Hispanic OR 0.23; 95% CI 0.08-0.56). IMRT was more likely to be used by providers in areas with a predominantly White or Hispanic population compared with providers in areas with a predominantly Black population (White OR 3.40; 95% CI 1.63-6.78; Hispanic OR 2.46; 95% CI 1.04-5.97). SBRT was less likely to be used in non-metro areas compared with metro areas (OR 0.28, 95% CI 0.12-0.56). The annual income measure was not associated with any RT modality. Providers in areas with predominantly Bachelor's degree attained were more likely to use PRT (Bachelor's degree as reference, OR 0.34; 95% CI 0.17-0.64) and less likely to use SBRT (OR 1.53; 95% CI 1.04-2.26), IMRT (OR 2.04; 95% CI 1.20-3.48), and 3DCRT (OR 1.52; 95% CI 1.04-2.22). No covariates were associated with BT use. We identified notable variations in RT delivery with multiple sociodemographic factors. A predominantly Black population was associated with a higher likelihood of PRT use, and BT use was not associated with any sociodemographic covariate. These findings might reflect reduced barriers to care afforded by the universal healthcare setting of Medicare or ongoing improvements in RT delivery with respect to previously identified health disparities. Additional work is needed to further elucidate these patterns of RT use and determine if they represent effective care.

Largest Real-World Data of Regional Nodal Irradiation Using Ultra-Hypofractionated 5-Fraction Adjuvant Radiation Therapy for Breast Cancer from a Single Institute in India

Safety data for ultra-hypofractionated (UHFRT) 5-daily fractions of the supraclavicular fossa (SCF) radiation therapy (RT) have been reported only on 384 patients treated in trial setting in UK-FAST-Forward (n = 286) and HYPORT study (n = 98). Internal Mammary nodal (IMN) RT has been reported only in 6 patients from HYPORT study. We report acute and late toxicities in largest real world regional nodal irradiation (RNI) cohort of not only with 5-daily but also with 5-weekly once RT regimen. Of 1435 patients (1463 breasts) who received 5-fraction RT in an IEC approved registry and prospectively followed, we report 999 consecutive cases receiving RNI with a median age of 49 years (IQR:42-56years). During pandemic all patients were treated with 5-fr regimens only to limit hospital visits whereas prior to and subsequently only in patients with advanced age or with issues precluding daily 15-20 treatments. Of these, 431 (43.1%) had locally advanced BC, and 280 (28%) patients presented with ≥cN2 disease. Median cT and pT sizes were 4cm (IQR:3-6cm) and 2.8cm (IQR:1.5-4cm) respectively. Tumor was Her2 positive in 290(29%) and TNBC in 220(22%). Of these 999 cases, 611 received NACT, 647 had mastectomy and 351 had breast conserving surgery (BCS). Simultaneous integrated tumor bed boost (SIB) was given in 341 (97.1%) of BCS cases. The fractionation used was 26 Gy/5-daily fractions (SIB = 32 Gy) in 762 and 28.5 Gy/ 5 once weekly fractionation (SIB = 33 Gy) in 232 cases. RNI included SCF in all 999 and IMN in 168 patients. Of the 831 cases not requiring IMN RT, 573 (70.4%) had 3D conformal RT (n = 573/831,70.4%) whereas Inverse-planned intensity modulated RT was used in 152/168 (90.4%) patients requiring IMN RT. All Mono-isocentric technique was used for all RNI cases treated with 3D CRT. Nearly half of the patients treated with SIB received additional boost dose with electrons (50.5%) and the remaining with IMRT. In these 999 patients treated with UHFRT the peak RTOG grade ≥II skin and pharyngeal toxicity was 7.2% and 8.1% respectively. Among the 341 BCS cases who received SIB with UHFRT, the RTOG acute grade II and III skin toxicity was seen in 6.6% and 0.3% cases respectively. The maximum skin toxicity at 2 weeks after completion of RT of grade ≥II was significantly higher with 5-weekly compared to daily regimen (16.1 vs 4.6, p<0.01). In contrast, the maximum pharyngeal toxicity of grade ≥II was significantly higher with 5-daily compared to weekly fractionation (8.8% vs 5.2%, p = 0.04). At median follow-up of 25 months (CI:23.6-26.3 months), none of our patients had developed symptomatic radiation pneumonitis, brachial plexopathy or any major cardiac event. Five-fraction adjuvant breast cancer RT is well tolerated with low acute toxicity burden even among patients requiring regional nodal irradiation. No brachial plexopathy was observed in cases treated with mono-isocentric RNI but longer follow-up is required to inform about the late toxicities and locoregional control rates.

Definitive and Salvage Radiotherapy Compared to Other Modalities for Laryngeal Carcinoma in Situ

We sought to analyze survival endpoints for laryngeal carcinoma in situ (CIS) undergoing definitive radiotherapy (RT) compared to other modalities. Usingour prospectively maintained head and neck cancer database, we identified laryngeal CIS patients treated between 6/2001 and 12/2021. We excluded low-grade dysplasia, CIS with any synchronous invasive squamous cell carcinoma (SCC) within 3 months of the initial CIS biopsy and cases with inadequate follow up. Patients were offered either definitive RT, CO2/KTP laser ablation, photodynamic therapy (PDT) or any sort of therapeutic excision. After first line treatment, follow-up includes visits every 3-6 months with laryngoscopy and biopsies as appropriate. For recurrent CIS beyond 6 months of first line treatment, we reported salvage therapies received and long-term outcomes were reported. Using Kaplan-Meier curves and log-rank test we investigated recurrence free (RFS), progression to invasive SCC free (IFS) and overall (OS) survival across treatment groups. Patients managed with salvage RT were compared to first line RT recipients. Atotal of 85 CIS cases were included: median age 65 years (IQR: 55-74), 73 males (85%) and 70 white (82.4%). 86% had a history of smoking with median pack year of 38 (IQR: 20-55) and 66% had a history of alcohol use. CIS was glottic in most of the cases (90.6%: 66% unilateral, 21% bilateral & 13% involved commissure); with only 9.4% in the supraglottic region. RT was used in 49.4% (n = 42) after biopsy (55%) or surgery (45%) with median dose of 63 Gy/28 fractions, mainly by 3D conformal RT (76%). The remaining 50.6% (n = 43) got therapeutic excision alone (commonly microflap excision) (46.5%), CO2/KTP laser (32.6%) or PDT (20.9%). Demographics and clinicopathological details were non-different between RT and non-RT patients except for Charlson comorbidity index: median 2 (IQR 1-3) in non-RT vs 1 (IQR 0-2) in 1ry RT; p = 0.007. After a median follow-up of 4.8 years (IQR 3.5), 51.8% had recurrent disease, 21.2% progressed to invasive SCC and 9.4% had laryngectomies mainly for invasive SCC after RT. First line RT had improved 2-(83% vs 39%) and 5-(74% vs 22%) year RFS vs non-RT therapies (p<0.001). Nevertheless, 2- and 5-year IFS (89% vs 98% and 80% vs 79%) and OS (92% vs 93% and 81% vs 77%) were non-significant among both (p>0.05 for all). Among non-RT cases with CIS recurrences, 12/35 (34%) had salvage RT. Following RT, salvage RT patients had similar 2- and 5-year RFS (81% vs 83% and 81% vs 74%) and IFS (81% vs 89% and 81% vs 80%) compared to first line RT (p>0.05 for all). All cases with CIS recurrences were salvaged successfully with 100% living with no CIS at latest follow-up. Laryngeal CIS can be treated with a wide range of modalities including 1ry RT which has better recurrence free survival. Nevertheless, non-RT recurrent CIS can be salvaged successfully with many options including RT with equivalent long-term results.

Association of Cardiac Dose with Cardiac Events and Survival for Locally Advanced Non-Small Cell Lung Cancer (LA-NSCLC) Treated with Concurrent Chemoradiotherapy (cCRT) in the Era of Immune Checkpoint Inhibitor (ICI) Consolidation

To assess the association of cardiac dose with post-cCRT cardiac events and survival among patients (pts) with LA-NSCLC after adoption of ICI consolidation, modern radiotherapy (RT) techniques, and data-driven cardiac constraints. This single-institution, multi-site retrospective study included 335 pts with LA-NSCLC treated with definitive cCRT (60-70 Gy) from October 2017 to December 2021. Pts were evaluated for ICI consolidation. Cardiac dose constraints included heart volume receiving ≥50 Gy (V50) <25% and mean heart dose (MHD) <20 Gy. Heart, left anterior descending artery (LAD), and left ventricle were autocontoured, manually reviewed, and edited. 21 dosimetric parameters (mean dose, max dose, and min dose to the hottest x% volume [Dx%(Gy); x from 5-95 in 5% intervals]) for each were extracted, as well as LAD V15. Baseline cardiovascular disease (bCVD) was defined as heart failure (HF), coronary artery disease, peripheral vascular disease, or cerebrovascular disease. Primary endpoint was post-cCRT major adverse cardiac events (MACE), defined as acute coronary syndrome, HF hospitalization/urgent visit, coronary revascularization, or cardiac death. Secondary endpoints were grade ≥3 cardiac events (CTCAE v5.0), overall survival (OS), cancer specific mortality (CSM), and other cause mortality (OCM). Competing risk regression was used for MACE and grade ≥3 cardiac events, and Cox regression for OS, CSM, and OCM. Median age was 68 years, 139 (41%) had bCVD, and 225 (67%) received consolidation ICI. Proton therapy was used in 117 (35%), intensity-modulated RT in 199 (59%), and 3D conformal RT in 19 (6%). Median MHD was 8.7 Gy (IQR 4.6-14.4) and median LAD V15 1.4% (IQR 0-22). Median follow-up was 39.5 months. 35 MACE events occurred; 1- and 2-year cumulative incidence (CI) were 4.2% and 9.5%. No cardiac dosimetric parameter associated with MACE after adjusting for bCVD and age (e.g., MHD sHR 0.98/Gy, 95% CI 0.93-1.03, p = 0.43) or within the following 3 subgroups: no bCVD, photon therapy, and ICI consolidation. 87 grade ≥3 cardiac events occurred; 1- and 2- year CI were 12.6% and 20.4%. Heart dose was not associated with grade ≥3 cardiac events after adjusting for bCVD, ECOG, and BMI (e.g., MHD sHR 1.00/Gy, 95% CI 0.97-1.03, p = 0.85) or within the 3 aforesaid subgroups. 183 OS events occurred, including 125 CSM and 58 OCM events. Multiple cardiac dosimetric parameters associated with worse OS on multivariable analysis (e.g., LAD V15 HR 1.01/%, 95% CI 1.00-1.02, p = 0.003), driven by associations with CSM (LAD V15 HR 1.02/%, p<0.001) but not OCM (LAD V15 HR 1.00/%, p = 0.73). Median OS was worse for LAD V15 ≥10% (22.2 vs 35.1 months, p = 0.004). Among pts with LA-NSCLC treated with cCRT after adoption of ICI consolidation, modern RT techniques, and cardiac constraints, post-cCRT cardiac events were common but showed no association with cardiac dose. Cardiac dose associated with OS, driven by an association with CSM and not OCM, which may not reflect cardiac toxicity.

The Association between Acute and Late Genitourinary and Gastrointestinal Toxicities: An Analysis of the PACE B Study

Acute gastrointestinal (GI) and genitourinary (GU) toxicity after prostate radiotherapy (RT) has been shown to be associated with late toxicity with 3D conformal RT. However, whether this association is present with modern approaches, such as stereotactic body radiotherapy (SBRT), remains unclear. We analyzed patients treated within the international phase III non-inferiority randomized control trial, PACE-B, to assess the association between acute and late toxicity following SBRT and conventional/moderately hypofractionated radiotherapy (CRT). We hypothesize that acute toxicity is significantly associated with equivalent late toxicity following prostate SBRT and CRT. We analyzed patients with GI and GU Common Terminology Criteria for Adverse Events (CTCAE) measurements in the acute (≤12 weeks post-RT) and late period (6-24 months post-RT). Using logistic regression, we analyze the association between G2+ acute GI and GU toxicities with equivalent late toxicities. Lasso variable selection was used to determine patient, tumor and treatment variables to include in the multivariable model. The area under the receiver operator characteristics curve (AUC) was used to evaluate the model's predictive performance. Of patients included in this analysis (n = 842), 414 were treated with SBRT and 428 with CRT. In univariable analysis (UVA), G2+ acute GU toxicity was significantly associated with developing G2+ late GU toxicity after SBRT (OR 4.63, 95% CI (2.96-7.25), p<0.0001) and CRT (OR 2.83, 95% CI (1.69-4.71), p<0.0001). This association remained significant in multivariable analysis (MVA). The models AUC for predicting G2+ late GU toxicity after SBRT was 0.73 (95% CI, 0.67-0.78) and 0.66 (95% CI, 0.59-0.73) following CRT. In UVA, G2+ acute GI toxicity was associated with developing G2+ late GI toxicity after SBRT (OR 3.67, 95% CI (1.91-7.03), p <0.0001) and CRT (OR 4.4, 95% CI (2.04-9.47), p<0.0001). This association also remained significant in MVA. The models AUC for predicting G2+ late GI toxicity after SBRT was 0.66 (0.95% CI, 0.57-0.75) and 0.64 (95% CI, 0.57-0.72) following CRT. In UVA analysis, G2+ baseline GU symptoms were also associated with developing G2+ late GU toxicity after SBRT (OR 7.59, 95% CI (2.72-21.19, p<0.0001) and CRT (OR 7.98, 95% CI (3.03-20.96), p<0.0001), and this continued to be significant in MVA. Acute toxicity remained associated with persistent late toxicity (≥2 G2+ late events) and late toxicity 12-24 months. Our study demonstrates an independent association between acute and late GU/GI toxicity in patients treated with SBRT and CRT for localized prostate cancer. Recognizing those at risk of late toxicity can provide an opportunity for early intervention to improve outcomes. G2+ acute toxicity should be considered an essential variable for predicting late GI/GU toxicity after prostate RT.

Shoulder Muscle Dosimetry and Post-Treatment Rehabilitation Utilization for Early-Stage Breast Cancer Patients

Rehabilitation services for recovery of impaired physical function following breast cancer treatments are largely underutilized. We previously found that breast cancer survivors treated with radiation who received higher radiation doses to the pectoralis major are more likely to self-report shoulder pain and disability. This study aims to address whether radiation dose delivered to the pectoralis major (Pmaj) and pectoralis minor (Pmin) are correlated with referrals for rehabilitation services post-treatment. A retrospective 1:1 matched case-control study was conducted for breast cancer patients who were and were not referred for breast or shoulder rehabilitation services between 2014-2019 at a single academic institution. Patients were included if they had a lumpectomy and adjuvant radiation without regional nodal irradiation. Cohorts were matched based on age, axillary surgery (none vs. sentinel lymph node biopsy (SLNB)), and use of radiation boost. We used non-parametric Mann-Whitney U tests to determine whether Pmaj or Pmin doses (mean, V50Gy, V45Gy, V40Gy, V35Gy, V30Gy, V20Gy) were different between the two groups. Muscle doses were converted to EQD2 assuming an α/β ratio of 2.5. In our study of 30 patients of a median age 57 years (IQR 12.75), 20 (66.67%) patients underwent SLNB in addition to lumpectomy. Median tumor size was 1.1cm (range 0.16 - 7.30cm). Stage was 0 for 11 patients (36.67%), I for 14 patients (46.67%), and II for 5 patients (16.67%). 3D conformal radiation was delivered to the whole breast with a moderately hypofractionated (n = 17) or conventionally fractionated regimen (n = 13). The most common rehabilitation diagnoses were lymphedema (n = 8), scar management (n = 7) and shoulder pain (n = 5). Mean dose to both the Pmaj (20.8Gy vs. 18.6Gy; p = 0.02) and Pmin (30.6Gy vs. 24.6Gy; p = 0.01) were significantly higher in patients who received post-treatment rehabilitation compared to those without. The V40Gy, V35Gy, V30Gy and V20Gy (all p<0.02) for the Pmin and V35Gy, V30Gy and V20Gy for the Pmaj (all p<0.04) were also significantly higher in those who underwent rehabilitation. In this cohort of patients with early-stage breast cancer, increased mean doses to the pectoralis muscles were correlated with increased use of rehabilitation services after radiation. Physicians might consider using these dosimetric data to complement clinical symptoms in the decision-making process for referrals for rehabilitation services. This may help facilitate earlier referral to rehabilitation interventions, which is important since early intervention is correlated with improved shoulder morbidity.

Conventional vs. Hypo-Fractionated, Radiotherapy for High-Risk Prostate Cancer (PCS5), Randomized, Non-Inferiority, Phase 3 Trial: Posthoc Analysis of IMRT vs. 3D-CRT Radiation Therapy Associated Toxicities

The Prostate Cancer Study number 5 (PCS5), is a multi-centric non-inferiority, phase 3, randomized controlled trial of high-risk prostate cancer patients of treated with either conventionally fractionated radiotherapy (CFRT) or hypofractionated radiotherapy (HFRT). The 7 years' pre-planned analysis showed that HFRT (68 Gy in 25 fractions) was as effective and well tolerated as CFRT (76 Gy in 38 fractions). In this posthoc analysis we aim to report the genitourinary (GU) and gastrointestinal (GI) toxicities associated with radiation therapy techniques: intensity-modulated radiotherapy (IMRT) and 3D-conformal radiotherapy (3D-CRT). PCS5 randomized patients in a 1:1 ratio to receive either CFRT or HFRT. All patients received long term neoadjuvant, concurrent and adjuvant androgen suppression, with a median duration of 24 months. The toxicities were reported as per the Common Terminology Criteria for Adverse Events version 4. Acute toxicities were defined as presenting ≤ 180 days post-RT start and delayed > 180 days. The cumulative acute and delayed GI and GU toxicities were classified in grade groups: grade 1 or higher (G1+), G2+, and G3+. For each grade group, acute and delayed, we performed multivariable logistic regression analyses, adjusting for age, CTV volume, diabetes, fractionation (CRFT or HFRT), hypertension, and stage < T3b or ≥ T3b. For efficacy analyses cox-regression was utilized. A p-value < 0.05 was considered significant. Three hundred twenty of the 329 patients enrolled in the trial were included in this posthoc analyses. The mean age was 71.4 ± 6.1 years, and the mean CTV volume (n = 219) was 47.25 ± 19.9 cc. IMRT was used in 195 (60.6%) patients and 3D-CRT in 125 (39.1%) patients. Multivariable logistic regression showed a significant difference in favor of IMRT for GI G2+ acute toxicity (OR = 0.285 [0.14-0.59]; CI: 95%; p<0.001) and GI G2+ delayed toxicity (OR = 0.202 [0.60-0.69]; CI: 95%; p = 0.01). There were no differences in G3+ GI or GU toxicities and there were no grade 4 toxicities. There were no differences in efficacy at 7 years between the two treatment technics. Outcomes for IMRT vs. 3D-CRT respectively, overall survival (81.5% vs 79.2%; HR: 0.92 [0.55-1.53]; CI: 95%; p-value: 0.74), distant metastasis free survival (90,7% vs 92.8%; HR: 1.4 [0.63-3.1]; CI: 95%; p-value: 0.42), prostate cancer mortality (95.8% vs. 92.2%; HR: 0.93 [0.32-2.67]; CI: 95%; p-value: 0.89), and biochemical failure (85.1% vs 88%; HR: 1.35 [0.72-2.52]; CI: 95%; p-value: 0.35). This is the first phase 3 randomized controlled trial assessing the use of HFRT vs. CFRT, exclusively in high-risk prostate cancer patients. Given that our efficacy data at 7 years follow-up establishes moderate HFRT as a new standard of care and no difference between IMRT and 3D-CRT, we strongly recommend that patients who are treated with EBRT should receive IMRT, given the reduced acute and delayed grade 2 or higher GI toxicities.

A Novel Approach to Support Quality Assurance (QA) of Intensity Modulated Neutron Therapy (IMNT)

Neutron therapy is a form of high linear energy transfer (LET) radiation treatment shown to be beneficial for the treatment of locally advanced head and neck cancers (HNC) resistant to low LET x-ray and proton therapy treatments. The Clinical Neutron Therapy System (CNTS) at our institution has been in clinical operation for over 35 years, and over 3,400 patients have been treated using 3D conformal neutron radiation therapy. In October of 2022, the clinical commissioning of IMNT was completed and the first-ever patient was treated. A novel patient specific quality assurance (PSQA) program has been developed to support IMNT. We present an analysis of our early experiences and PSQA findings for the first 16+ patients treated with IMNT. Our pre-treatment IMNT PSQA program includes (1) ionization chamber measurements, (2) a log-file analysis of treatment delivery, and (3) a γ-analysis of the expected and measured doses (fluences) from a novel positron emission portal imaging system based on 12C(n,2n)11C reactions. Patient setup is confirmed on a daily basis with kV portal imaging. We use a modulation factor (MF), defined as the total number of monitor units (MU)/prescribed dose (cGy) per fraction, to identify and help anticipate IMNT plans that may fail our PSQA program. We have found that IMNT treatments for large, irregularly shaped treatment volumes (e.g., chest wall or head and neck cancers that require treatment of nodes in the lower neck) are more likely to fail PSQA when the MF exceeds 3 MU/cGy. For smaller, more spherical treatment volumes (e.g., base of tongue cancers), plans with a MF up to 3.5 MU/cGy pass our PSQA criteria. Re-optimized plans subsequently passed PSQA with insignificant or no change in tumor coverage and organ-at-risk (OAR) dose. Re-optimized plans also reduced the total number of MU and number of segments, which has the added benefit of decreasing the overall treatment time and patient time on the table. About 10% of early IMNT patients have required plan re-optimization. Our pre-treatment clinical PSQA program and workflow provides useful information to guide IMNT treatment planning and delivery, and helps ensure the safe and accurate delivery of IMNT. Our early experiences suggest IMNT plans with smaller MF values are more likely to pass PSQA than plans with larger values of the MF.

Risk of Cardiac-Specific Mortality in Patients with Lymphoma Treated with Radiotherapy

The mainstays of treatment for Non-Hodgkin (NHL) and Hodgkin (HL) lymphoma are chemotherapy, radiotherapy (RT), or a combination of both. Thanks to improvements in treatment options many patients outlive their diagnosis by several decades. As treatments are de-intensified and cardiac sparing techniques have improved, the impact of RT on cardiac mortality should be re-visited. In this study, we sought to investigate the potential association between thoracic irradiation and cardiac-specific mortality (CSM) in patients with lymphoma. We hypothesized that receipt of RT would be associated with higher risk of cardiac death. The Surveillance Epidemiology and End Results (SEER) database was queried to identify all patients with HL and NHL with a thoracic primary site from 1975 to 2018. Kaplan Meier estimators were used to analyze cardiac-specific survival. Cohorts were balanced using inverse probability treatment weighing (IPTW). Hazard ratios were calculated using multivariate cox regression analysis. The following treatment eras were defined for analysis: pre-1995, 1995-2003, post-2003, to roughly correspond to the adoption of 3D conformal RT (3DCRT) and intensity-modulated RT (IMRT). We identified 10,602 patients, of which 8,088 (76%) had NHL and 2,514 (24%) had HL. Seventy-three percent of patients received chemotherapy and 38% received RT. Median follow up was 11.2 years. Forty-eight percent of patients were alive at last follow up, 6.6% had died from cardiac-specific causes, and 45% had died of other causes. Patients who received RT were had a lower risk of CSM (HR = 0.64, p < 0.01). However, IPTW survival analysis revealed no difference in the risk of cardiac death between the treatment cohorts (HR = 1.00, p = 0.99). Multivariate cox regression analysis identified female sex (HR = 0.73, p <0.01), age younger than 40 (HR = 0.27, p <0.01), and diagnosis after 1995 (HR = 0.31, p <0.01) to be associated with a lower CSM. In patients who received RT, we found that the risk of CSM was a higher (HR = 2.66, p <0.01) in those treated in the pre-1995 era and lower (HR = 0.32, p < 0.01) in the post-2003 era when compared to patients treated between 1995-2003. Additionally, receipt of RT was associated with a lower risk of all-cause mortality (HR 0.82, p<0.01). Our IPTW analysis shows that patients with thoracic lymphoma treated with RT have a similar risk of cardiac death to patients who did not receive RT, and an improved OS. Known cardiovascular risk factors like male sex and older age were associated with higher risk of cardiac death in patients receiving RT. We also found that patients treated with RT pre-1995 had higher CSM compared to those treated in 1995-2003 and those treated after 2003 had the lowest CSM, possibly in part attributable to the adoption of newer RT techniques. These findings may help clinicians counsel patients with lymphoma on the optimal modality of therapy and the possibility for late treatment effects in the modern era.

Complete patient exposure during paediatric brain cancer treatment for photon and proton therapy techniques including imaging procedures.

In radiotherapy, especially when treating children, minimising exposure of healthy tissue can prevent the development of adverse outcomes, including second cancers. In this study we propose a validated Monte Carlo framework to evaluate the complete patient exposure during paediatric brain cancer treatment. Organ doses were calculated for treatment of a diffuse midline glioma (50.4 Gy with 1.8 Gy per fraction) on a 5-year-old anthropomorphic phantom with 3D-conformal radiotherapy, intensity modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT) and intensity modulated pencil beam scanning (PBS) proton therapy. Doses from computed tomography (CT) for planning and on-board imaging for positioning (kV-cone beam CT and X-ray imaging) accounted for the estimate of the exposure of the patient including imaging therapeutic dose. For dose calculations we used validated Monte Carlo-based tools (PRIMO, TOPAS, PENELOPE), while lifetime attributable risk (LAR) was estimated from dose-response relationships for cancer induction, proposed by Schneider etal. Out-of-field organ dose equivalent data of proton therapy are lower, with doses between 0.6 mSv (testes) and 120 mSv (thyroid), when compared to photon therapy revealing the highest out-of-field doses for IMRT ranging between 43 mSv (testes) and 575 mSv (thyroid). Dose delivered by CT ranged between 0.01 mSv (testes) and 72 mSv (scapula) while a single imaging positioning ranged between 2 μSv (testes) and 1.3 mSv (thyroid) for CBCT and 0.03 μSv (testes) and 48 μSv (scapula) for X-ray. Adding imaging dose from CT and daily CBCT to the therapeutic demonstrated an important contribution of imaging to the overall radiation burden in the course of treatment, which is subsequently used to predict the LAR, for selected organs. The complete patient exposure during paediatric brain cancer treatment was estimated by combining the results from different Monte Carlo-based dosimetry tools, showing that proton therapy allows significant reduction of the out-of-field doses and secondary cancer risk in selected organs.