PurposeAs the incidence of stage II-III locally advanced rectal cancer (LARC) rises in younger patients, we sought to investigate the risk of sexual dysfunction following radiation therapy (RT) in younger men.MethodsMen ≤50 years old diagnosed with LARC between 1995–2019 at a single institution were retrospectively evaluated. Primary outcomes of erectile dysfunction (ED) and ejaculatory dysfunction (EjD) were defined via ICD codes and clinical evaluation. Cumulative incidences were calculated with death as a competing risk. Subdistribution hazard ratios from competing risk regression models were used. Dosimetric parameters to organs at risk were extracted to suggest dose constraints to prevent sexual dysfunction.ResultsThe study included 429 men: 350 received concurrent chemoradiation therapy (CXRT) as part of their treatment, and 79 did not receive RT. The two groups were similar with respect to age at diagnosis, stage, and medical comorbidities associated with sexual dysfunction (p>0.05). With a median follow-up of 6.3 years, the 5-year cumulative incidence of ED in the CXRT group was 25% (95%CI 20-30%) compared to 3.9% (95%CI 1.0-10%) in the no RT group (p<0.001). On multivariable analysis, CXRT maintained statistical significance as an independent risk factor for ED (HR 3.55, 95% CI 1.34-9.44, p=0.011). Within the CXRT group, inguinal coverage in the treatment fields was an independent risk factor for ED (HR 2.38, 95% CI 1.30-4.34, p=0.005), and greater distance from the anal verge had a protective effect. No difference was found in EjD between the 2 groups.ConclusionCXRT independently increases risk of ED but not EjD in patients treated for rectal cancer. Technique and target location may impact sexual dysfunction, possibly due to greater radiation dose to the genitalia. These findings may aid in establishing new constraints and promote counseling of young male patients on risks of sexual dysfunction.

3518 Background: Definitive chemoradiation (CRT) is a highly effective, organ-preserving treatment for localized anal squamous cell carcinoma (ASCC). However, a subset of patients experience locoregional failure, leading to unfavorable oncologic outcomes despite salvage surgery. Circulating tumor DNA (ctDNA) has emerged as a promising tool for monitoring treatment efficacy and predicting prognosis; however, there is a paucity of studies evaluating the baseline detectability and kinetics of tumor-informed ctDNA assays in ASCC. Methods: Patients with ASCC ( N =88) undergoing definitive CRT provided prospective consent for longitudinal ctDNA monitoring using a personalized, tumor-informed ctDNA assay (Signatera, Natera, Inc.). ctDNA testing was assessed at three key time points: pre-treatment (any time before CRT to within 5 days after initiation), mid-treatment (from >5 days after initiation to <7 days before completion), and post-treatment (>7 days before completion to 42 days after CRT). Surveillance testing continued every three months. Changes in ctDNA levels were analyzed in relation to clinical outcomes. Locoregional failure (LRF) was assessed using competing risk regression, stratified by ctDNA status (positive vs. negative). ctDNA results were also correlated with progression-free survival (PFS). Results: Pre-treatment ctDNA was detected in 79% of patients, with 92% achieving ctDNA-negativity at post-treatment (Table 1). Over a median follow-up of 18 months (IQR 11–26), 7 patients experienced LRF, and 5 experienced distant failure. The cumulative LRF incidence was 0% among patients with ctDNA negativity by mid-treatment. Conversely, 26% of patients with ctDNA positivity at mid-treatment and 61% of patients with ctDNA positivity at post-treatment experienced LRF, respectively. Estimated one-year PFS was 100% for patients who achieved ctDNA negativity by mid-treatment. In contrast, patients who remained ctDNA-positive at mid-treatment and post-treatment had estimated one-year PFS rates of 81% and 44%, respectively, from the date of the corresponding ctDNA test. Among patients who achieved ctDNA negativity but subsequently developed molecular recurrence during the surveillance period ( N =7), all developed disease recurrence. Molecular recurrence predated clinical or radiographic evidence of recurrence in all instances. Conclusions: This tumor-informed ctDNA assay demonstrates high baseline detectability and rapid clearance during CRT, with molecular clearance correlating with favorable outcomes in ASCC. Notably, ctDNA-based detection of molecular recurrence consistently precedes conventional clinical and radiographic indicators of disease recurrence. Further validation in large, prospective cohorts is warranted. Pre -Treatment Mid -Treatment Post- Treatment Positive 61 (79%) 29 (47%) 6 (8%) Negative 16 (21%) 33 (53%) 67 (92%) Unknown 11 26 15

PURPOSE:The 5-year results of the FAST-Forward trial demonstrated noninferiority of local tumor control using a 26 Gy in 5 fraction regimen compared with 40 Gy in 15 fractions for breast cancer patients receiving adjuvant whole breast radiation therapy (WBRT) with or without a sequential conventionally fractionated tumor bed boost (2 Gy per fraction). Here, we reported our institutional experience using the FAST-Forward regimen with a novel sequential boost regimen of 5.2 Gy in 1 fraction or 10.4 Gy in 2 fractions. METHODS AND MATERIALS:Patients with nonmetastatic invasive breast cancer or ductal carcinoma in situ treated with adjuvant WBRT of 26 Gy in 5 fractions from January 7, 2019, to January 6, 2022, were identified from an institutional database. Clinical outcomes, including adverse events, disease control, and patient-reported outcomes, were collected. Survival outcomes were estimated using the Kaplan-Meier method. Associations between toxicities and clinicopathologic and treatment characteristics were assessed using logistic regression. RESULTS:A total of 311 consecutive patients were included; the use of a 1- or 2-fraction boost was left to the discretion of the treating physicians (54% 1-fraction, 8.7% 2-fraction, and 38% no boost). Median follow-up was 32 months. Overall survival and local recurrence-free survival probabilities at 36 months were 96% (95% CI, 94-99) and 93% (95% CI, 90-97), respectively. Acute and late toxicities occurred at a higher rate in the 2-fraction versus 1-fraction and no boost groups (37.4%, 10.8%, and 12.2% [acute] and 22.7%, 8.6%, and 7.9% [late], respectively). Boost receipt, greater boost volume, 15× energy, increasing breast V95%, and bolus use were associated with the risk of acute grade ≥ 2 toxicities. CONCLUSION:A 5-fraction ultrahypofractionated WBRT regimen for early-stage breast cancer with either no boost or a single-fraction boost of 5.2 Gy resulted in excellent disease control and acceptable toxicity. Increased toxicity was observed with a boost of 10.4 Gy in 2 fractions and is no longer used at our institution.

e12516 Background: Landmark studies of accelerated partial breast irradiation (APBI) included patients with DCIS, but with limited guidance regarding subgroups of in situ disease. Suitability criteria defined by national guidelines for APBI are narrowly constrained among those with DCIS, and controversy persists regarding optimal patient selection. Here, we report disease outcomes for a heterogeneous cohort of patients with DCIS who received APBI. Methods: Using a prospectively maintained institutional database, we identified patients with DCIS who underwent lumpectomy and adjuvant APBI from 2000 to 2022. Clinicopathologic characteristics were collected, and patients were classified as suitable, cautionary, or unsuitable for APBI by the latest American Society for Radiation Oncology (ASTRO) criteria. Outcomes of interest included local recurrence (LR), overall survival (OS), and follow up time. Cumulative incidence functions were calculated to estimate the incidence of LR over time. All statistical analyses were performed in R version 4.2.2. Results: The cohort comprised 176 patients, median age 60 years (IQR 52, 66). Median DCIS size was 9 mm (IQR 4, 15 mm), and approximately 20% had multifocal disease. Most patients had negative final surgical margins (160, 91%), with 10 patients having ≤2 mm margins and 6 having ≤1 mm margins for DCIS. 18 (10%) patients had nuclear grade I disease, 111 (63%) had grade II disease, and 33 (19%) had grade III disease, with a small subset classified as grade I-II or II-III. Most patients (161, 91%) had ER+ DCIS, and 72 (41%) received endocrine therapy. By ASTRO criteria, 118 (67%) patients were suitable for APBI, 57 (32%) cautionary, and 1 (0.6%) was unsuitable. At a median 24 months of follow up (range 2 to 127 months) we observed only one LR, yielding a 2-year LR rate of 0.6%. The LR occurred in the cautionary group, yielding a 2-year LR rate of 1.8% for the cautionary subset. The patient with LR was 56 years old, with 24 mm of high grade DCIS, ER+, with lumpectomy to negative margins, and did not receive endocrine therapy. No breast cancer mortality events were observed. Conclusions: Our early-term results exhibit excellent local control for patients with DCIS who received lumpectomy and APBI, even among those classified as “cautionary” by national guidelines. Although our findings are limited by short follow up, these results suggest that broadening the application of APBI for patients with DCIS may warrant further investigation.

Purpose We sought to identify factors associated with second pelvic malignancies (SPM), as well as second nonpelvic malignancies (SNPM), after chemotherapy with or without radiation therapy (RT) for locally advanced rectal cancer (LARC). Methods and Materials Patients diagnosed with stage II-III LARC. Cumulative incidence of second malignancies was analyzed using a 2-year landmark analysis with death as a competing risk. Results Among 2624 patients with LARC, 460 received chemotherapy and 2164 received RT with concurrent chemotherapy (CXRT). With a median follow-up of 6 years in both cohorts, 7 SPMs were diagnosed in the chemotherapy cohort and 68 SPMs were diagnosed in the CXRT cohort. The 5- and 10-year cumulative incidence of SPM in the chemotherapy cohort were 2.3% and 4.2%, respectively, compared with 2.1% and 5.8% in the CXRT cohort (P = .3). Older age (>50) was significantly associated with development of SPM on multivariable analysis (hazard ratio [HR], 3.03; P = .005). Intensity-modulated RT was associated with reduced risk of SPM compared with conventional RT (P = .014). Of the total 75 SPMs, 72 were genitourinary cancers and only 3 were sarcomas. For SNPM, the 10-year cumulative incidence was significantly higher in the CXRT group compared with the chemotherapy group (11.0% vs 4.4%). Older age (>50) was associated with increased risk of SNPM (HR, 2.48; P < .001). Diabetes was associated with more SNPM (HR, 1.51; P = .028), whereas abstaining from tobacco was associated with decreased risk of SNPM (HR 0.63, P = .013). Conclusion The CI of SPM was not significantly higher in patients who received CXRT compared with chemotherapy alone for LARC. SNPM CI was increased in the CXRT compared with chemotherapy-alone cohort, and higher in smokers, diabetics, and patients >50 years.

Purpose/Objective(s) For breath-hold Cone Beam CT (CBCT) imaging on a conventional linear accelerator (LINAC), multiple breath holds are typically required to acquire complete projections for faithful image reconstruction. The long acquisition leads to motion artifacts on the CBCT images and reduces patient comfort during the treatment. This study introduces a new diffusion-based image reconstruction method for ultra-fast short-arc CBCT acquisition. Materials/Methods To facilitate short-arc image reconstruction, we trained a patient-specific Denoising Diffusion Probabilistic Model (DDPM) model using the patient's 4DCT axial images, augmented by image shifting in the anterior-posterior and lateral directions. To expedite the model training process, the images were downsampled to 256 × 256 resolution. Training the model required 2 days on 2 Nvidia Quadro RTX 8000 GPUs with 48GB of memory each. We employed a linear noise schedule with 1000 diffusion steps in the DDPM. Utilizing the trained model as prior knowledge, we applied it in short-arc CBCT reconstructions with 90-degree and 45-degree limited angle data acquisition. A conjugate-gradient (CG)-guided diffusing sampling scheme was proposed to initiate the diffusion-based CBCT reconstruction process from a middle step using noise-blended CG reconstructed images. Our patient-specific model aims to minimize hallucination, while the CG-guided backward diffusion sampling scheme expedites the reconstruction process. For validation, we performed a simulation to reconstruct the patient's free breathing CT under cone beam geometry, aided by a patient-specific diffusion model trained by the patient's 4DCT images. We assessed the reconstructed image quality using Peak Signal-to-Noise Ratio (PSNR) and Structural Similarity Index (SSIM) metrics, comparing against the conventional iterative CG least squares (CGLS) methods. Results The CBCT acquisition can be completed within a breath-hold with times of 15 seconds for the 90-degree short-arc and 7.5 seconds for the 45-degree short-arc. Compared to the traditional iterative CGLS reconstruction, PSNR improved from 22.1 to 26.6, SSIM from 0.87 to 0.89, and MAE decreased from 35.0 to 18.3 for 90-degree reconstruction and PSNR improved from 18.2 to 22.7, SSIM from 0.83 to 0.85, and MAE decreased from 53.5 to 31.1 for 45-degree reconstruction. With this method, the CBCT reconstruction of image size 256 × 256 × 110 with a voxel size of 2 × 2 × 1.25 mm took approximately 3 minutes using 2 Nvidia Quadro RTX 8000 GPUs with 48GB of memory. Conclusion Leveraging patient-specific prior knowledge through diffusion models enables ultra-fast short-arc CBCT image acquisition, enhancing image quality, reducing motion artifacts, and increasing patient comfort during treatment.

Purpose/Objective(s) Ablative radiation therapy (A-RT) defined as a prescribed dose of ~100 Gy BED10 can achieve durable freedom from local failure (FFLF) and may improve overall survival (OS) versus non-ablative RT for locally advanced pancreas cancer (LAPC). The optimal technique for delivering A-RT is uncertain. Materials/Methods We retrospectively compared A-RT outcomes among LAPC patients treated at 2 U.S. institutions with different A-RT techniques excluding those who had surgery at any time. Institution (Inst) A used stereotactic magnetic resonance (MR)-guided online adaptive radiation therapy (SMART) with automatic beam gating on a 0.35T MR-Linac prescribing 5 fx (50 Gy, 95.6%; 45 Gy 4.4%). Inst B used a hypofractionated ablative RT (HART) delivered on a CBCT-guided Linac with respiratory gating and selective offline replanning, prescribing 25 fx (75 Gy, 80.8%) or 15 fx (67.5 Gy, 19.2%). Elective coverage including the celiac trunk and SMA was routine at both Inst A and B. Clinical characteristics were compared using Chi square or Fisher’s exact test. FFLF as per RECIST, freedom from distant failure (FFDF), and overall survival (OS) were estimated from RT with the Kaplan-Meier method and log-rank test. Cox proportional hazards regression model was used for univariate (UVA) and multivariate (MVA) analysis. Results 211 patients (n = 91, SMART; n = 120, HART) were evaluated. Similar baseline characteristics (SMART vs. HART) included maximum tumor size (3.7 vs. 3.8 cm), median pre-RT CA19-9 level (55 vs. 70 U/mL), induction FOLFIRINOX or gemcitabine/nab-paclitaxel use (82.4% vs. 85.8%), and median induction chemo duration (3.9 vs. 3.7 months). Significant differences (SMART vs. HART) included median age (71 vs. 68 years; P = 0.004), ECOG performance status 0 (41.8% vs. 90.0%; p<.001), head tumor (80.2 vs. 62.5%; P = 0.005), and N+ (25.3% vs. 42.5%; p<.001). SMART plans were hotter (e.g., GTV V120% 14.5 vs. 0.0 cc; p<.001) with higher target coverage (e.g., median GTV D90 scaled 101.1% vs. 84.5%; p<.001). Median follow-up from A-RT was 12.0 vs. 17.5 months (p<.001). 2-yr FFLF, FFDF, and OS for SMART vs. HART were 85.6% vs. 69.0% (p<.001), 30.3% vs. 26.5% (P = 0.513), and 31.0% vs. 35.3% (P = 0.056). On MVA, worse FFLF was associated with 15-25 vs. 5 fractions (HR 4.982, 95% CI = 1.105-22.454) and induction non-FOLFIRINOX vs. FOLFIRINOX (HR 2.010 (95% CI = 1.023-3.949) while worse OS was associated with higher GTV V120% (HR 1.016, 95% CI = 1.001-1.031). Acute grade >3 toxicity was similar (3.3% vs. 5.8%; P = 0.390) while less late grade >3 toxicity occurred after SMART (2.2% vs. 9.2%; P = 0.037). Conclusion Favorable 2-yr FFLF and OS were achieved after induction chemo and A-RT for LAPC regardless of delivery technique. Higher FFLF after SMART may be related to higher GTV coverage, albeit this was not significant on MVA. Despite this, OS was similar potentially due to more unfavorable baseline characteristics among the SMART cohort. Lower rates of late grade >3 toxicity may have been facilitated by online adaptive RT.

Objective. We report on paraspinal motion and the clinical implementation of our proprietary software that leverages Varian’s intrafraction motion review (IMR) capability for quantitative tracking of the spine during paraspinal SBRT. The work is based on our prior development and analysis on phantoms. Approach. To address complexities in patient anatomy, digitally reconstructed radiographs (DRR’s) that highlight only the spine or hardware were constructed as tracking reference. Moreover, a high-pass filter and first-pass coarse search were implemented to enhance registration accuracy and stability. For evaluation, 84 paraspinal SBRT patients with sites spanning across the entire vertebral column were enrolled with prescriptions ranging from 24 to 40 Gy in one to five fractions. Treatments were planned and delivered with 9 IMRT beams roughly equally distributed posteriorly. IMR was triggered every 200 or 500 MU for each beam. During treatment, the software grabbed the IMR image, registered it with the corresponding DRR, and displayed the motion result in near real-time on auto-pilot mode. Four independent experts completed offline manual registrations as ground truth for tracking accuracy evaluation. Main results. Our software detected ≥1.5 mm and ≥2 mm motions among 17.1% and 6.6% of 1371 patient images, respectively, in either lateral or longitudinal direction. In the validation set of 637 patient images, 91.9% of the tracking errors compared to manual registration fell within ±0.5 mm in either direction. Given a motion threshold of 2 mm, the software accomplished a 98.7% specificity and a 93.9% sensitivity in deciding whether to interrupt treatment for patient re-setup. Significance. Significant intrafractional motion exists in certain paraspinal SBRT patients, supporting the need for quantitative motion monitoring during treatment. Our improved software achieves high motion tracking accuracy clinically and provides reliable guidance for treatment intervention. It offers a practical solution to ensure accurate delivery of paraspinal SBRT on a conventional Linac platform.

Introduction: The rate of isolated locoregional recurrence after surgery for pancreatic adenocarcinoma (PDAC) approaches 25%. Ablative radiation therapy (A-RT) has improved outcomes for locally advanced disease in the primary setting. We sought to evaluate the outcomes of salvage A-RT for isolated locoregional recurrence and examine the relationship between subsequent patterns of failure, radiation dose, and treatment volume. Methods: We conducted a retrospective analysis of all consecutive participants who underwent A-RT for an isolated locoregional recurrence of PDAC after prior surgery at our institution between 2016 and 2021. Treatment consisted of ablative dose (BED10 98–100 Gy) to the gross disease with an additional prophylactic low dose (BED10 < 50 Gy), with the elective volume covering a 1.5 cm isotropic expansion around the gross disease and the circumference of the involved vessels. Local and locoregional failure (LF and LRF, respectively) estimated by the cumulative incidence function with competing risks, distant metastasis-free and overall survival (DMFS and OS, respectively) estimated by the Kaplan–Meier method, and toxicities scored by CTCAE v5.0 are reported. Location of recurrence was mapped to the dose region on the initial radiation plan. Results: Among 65 participants (of whom two had two A-RT courses), the median age was 67 (range 37–87) years, 36 (55%) were male, and 53 (82%) had undergone pancreaticoduodenectomy with a median disease-free interval to locoregional recurrence of 16 (range, 6–71) months. Twenty-seven participants (42%) received chemotherapy prior to A-RT. With a median follow-up of 35 months (95%CI, 26–56 months) from diagnosis of recurrence, 24-month OS and DMFS were 57% (95%CI, 46–72%) and 22% (95%CI, 14–37%), respectively, while 24-month cumulative incidence of in-field LF and total LRF were 28% (95%CI, 17–40%) and 36% (95%CI 24–48%), respectively. First failure after A-RT was distant in 35 patients (53.8%), locoregional in 12 patients (18.5%), and synchronous distant and locoregional in 10 patients (15.4%). Most locoregional failures occurred in elective low-dose volumes. Acute and chronic grade 3–4 toxicities were noted in 1 (1.5%) and 5 patients (7.5%), respectively. Conclusions: Salvage A-RT achieves favorable OS and local control outcomes in participants with an isolated locoregional recurrence of PDAC after surgical resection. Consideration should be given to extending high-dose fields to include adjacent segments of at-risk vessels beyond direct contact with the gross disease.

Purpose/Objective(s) A variety of independent studies reported that significant intrafractional patient motion can occur in paraspinal SBRT despite the use of immobilization. However, analysis of the dosimetric impact of such motion on clinical patients is limited in the literature. This work aims to provide the analysis based on our prior work on MV-KV imaging based quantitative intrafractional motion tracking during paraspinal SBRT. Materials/Methods Thirty-one patients undergoing paraspinal SBRT at three network clinics were randomly selected for this study. The selected patients had disease sites covering all regions of the spine, and there were no exclusion criteria. SBRT was planned with a 9-field IMRT technique using an in-house automated expedited constrained hierarchical optimization system. During treatment delivery, simultaneous MV-KV image pairs were continuously acquired using the iTools capture software. A proprietary software was used to retrospectively register those image pairs with the corresponding references based on normalized cross-correlation and to triangulate the 3D intrafractional motion throughout the treatment. When applicable, manual registration was performed to verify and correct the software’s automatic registration. To assess motion impact, treatment plans were recalculated with isocenter corrections based on 3D shifts determined from associated MV-KV image pairs. Dosimetric parameters of target volumes and relevant organs at risk (OARs) were analyzed. Results The dosimetric impact generally increased with greater 3D motion magnitude. For PTV, V100% was the most affected by intrafractional motion, followed by Dmax and V95%. 16% of patients experienced a reduction in V100% of at least 3.4%, with an average reduction of 6.3% and a maximum reduction of 12.2%. For GTV or CTV, 16% of patients had a change of minimum dose to the coolest 0.035 cc by at least 1.2 Gy with a maximum of 2.4 Gy. Regarding OAR doses, 26% of patients experienced an increase in spinal cord or cauda Dmax of at least 1 Gy, with a maximum increase of 4.8 Gy and 2.7 Gy for the cord and cauda, respectively. The maximum increase in the hottest 0.035 cc of the esophagus was 4.8 Gy. In 42% of all patients, at least one OAR dose for the actual delivery exceeded a dose constraint met during planning. Conclusion Intrafractional patient motion during paraspinal SBRT significantly compromises planned dosimetry due to the high conformality in plans, steep dose gradients, and proximity of critical OARs. Continuous monitoring and correcting such motion during treatment delivery support optimal treatment outcomes.

BACKGROUND AND PURPOSE:A retrospective single-center analysis of the safety and efficacy of reirradiation to 40 Gy in 5 fractions (reSBRT) in patients previously treated with stereotactic body radiotherapy to the spine was performed. METHODS:We identified 102 consecutive patients treated with reSBRT for 105 lesions between 3/2013 and 8/2021. Sixty-three patients (61.8%) were treated to the same vertebral level, and 39 (38.2%) to overlapping immediately adjacent levels. Local control was defined as the absence of progression within the treated target volume. The probability of local progression was estimated using a cumulative incidence curve. Death without local progression was considered a competing risk. RESULTS:Most patients had extensive metastatic disease (54.9%) and were treated to the thoracic spine (53.8%). The most common regimen in the first course of stereotactic body radiotherapy was 27 Gy in 3 fractions, and the median time to reSBRT was 16.4 months. At the time of simulation, 44% of lesions had advanced epidural disease. Accordingly, 80% had myelogram simulations. Both the vertebral body and posterior elements were treated in 86% of lesions. At a median follow-up time of 13.2 months, local failure occurred in 10 lesions (9.5%). The 6- and 12-month cumulative incidences of local failure were 4.8% and 6%, respectively. Seven patients developed radiation-related neuropathy, and 1 patient developed myelopathy. The vertebral compression fracture rate was 16.7%. CONCLUSION:In patients with extensive disease involvement, reSBRT of spine metastases with 40 Gy in 5 fractions seems to be safe and effective. Prospective trials are needed to determine the optimal dose and fractionation in this clinical scenario.

Purpose/Objective(s) Invasive lobular carcinoma (ILC) represents 10-15% of invasive breast cancers with limited representation among trials of accelerated partial breast irradiation (APBI). Contemporary guidelines advise against treating ILC with APBI given a paucity of supportive evidence. Here, we evaluated oncological outcomes among patients with ILC treated with APBI. Materials/Methods Patients treated from 2000 – 2022 with APBI following breast conserving surgery for ILC (or mixed ILC with other histologies) were ascertained from a prospectively-maintained institutional database. All patients received external beam APBI to 40Gy in 10 daily fractions. Outcomes of interest included local recurrence (LR) and overall survival (OS). Results Of 1248 patients who underwent PBI at our center, 132 (11%) had ILC, either exclusively or mixed with another histology, comprising the study cohort (median age 63). Median tumor size was 1.1cm (IQR = 0.8, 1.5), nearly all had estrogen receptor positive disease (99%) and received endocrine therapy (91%), and most underwent sentinel node biopsy (89%) with the remainder having no axillary surgery. At 530 person-years and a median follow-up of 39 months, two LRs were observed yielding a 48-month cumulative incidence of LR of 3.0% (95% CI = 0.56 – 9.5%). Both events arose in patients with mixed lobular histology (none arose in patients with pure ILC). Two unrelated deaths were also observed yielding a 48-month overall survival of 98% (95% CI: 95% - 100%) Conclusion Among patients with ILC who received APBI followed BCS, we observed a 4-year LR rate of 3%. No regional or distant recurrences were observed, and overall survival was excellent. The safety of APBI for ILC will require confirmation among larger trials with longer follow-up, although the excellent outcomes observed here are consistent with those seen for invasive ductal carcinomas among contemporary trials of APBI.

BACKGROUND AND PURPOSE:We investigate discrepancies in the assessment of treatment-related symptoms in lung cancer between healthcare professionals and patients, and factors contributing to these discrepancies. MATERIALS AND METHODS:Data from 515 participants in the REQUITE study were analysed. Five symptoms (cough, dyspnoea, bronchopulmonary haemorrhage, chest wall pain, dysphagia) were evaluated both before and after radiotherapy. Agreement between healthcare professionals and people with lung cancer was quantified using Gwet's-AC2 coefficient. The influence of clinical variables, comorbidities, and quality-of-life outcomes on agreement was examined through stratified analyses. RESULTS:We found varying levels of agreement between healthcare professionals and people with lung cancer. Bronchopulmonary haemorrhage and dysphagia exhibited very good agreement (meanAC2 > 0.81), while cough and chest wall pain showed substantial agreement (meanAC2 = 0.64 and 0.76, respectively). Dyspnoea had the lowest agreement (meanAC2 = 0.59), with prior chemotherapy significantly reducing agreement levels. Chronic obstructive pulmonary disease (COPD) and early cancer stages also contributed to discrepancies in dyspnoea assessments. Regarding quality-of-life, the most relevant factor was fatigue, which reduced agreement in the assessment of dyspnoea (AC2 = 0.55 vs 0.70), dysphagia (AC2 = 0.48 vs 0.69), cough (AC2 = 0.58 vs 0.82), and chest wall pain (AC2 = 0.77 vs 0.91). CONCLUSIONS:Our findings indicate strong alignment between healthcare professionals' and people with lung cancer evaluations of observable treatment-related symptoms, but less consistency for subjective symptoms such as dyspnoea. Factors such as prior chemotherapy, COPD, and cancer stage should be considered when interpreting symptom assessments. Furthermore, our study underscores the importance of integrating quality-of-life considerations, particularly fatigue, into symptom evaluations to mitigate potential biases in symptom perception.

BACKGROUND:Palmar-plantar erythrodysesthesia (PPE) is a slowly developing cutaneous reaction commonly experienced by patients treated with fluoropyrimidines. While erythrodysesthesia normally presents in a palmar-plantar distribution, it can also present with genital involvement, but this presentation is likely underreported and incorrectly attributed to an acute reaction from radiation therapy. This article aims to define erythrodysesthesia of the penis and scrotum as a rare but significant side effect of capecitabine.CASE PRESENTATION:We identified five cases of moderate to severe penis and scrotal erythrodysesthesia over a 2-year period at a large tertiary cancer center, representing an estimated incidence of 3.6% among male patients with rectal cancer who were treated with fluoropyrimidine-based chemoradiation within our institution.CONCLUSIONS:Improved understanding of erythrodysesthesia involving the penis and scrotum can facilitate early identification and treatment of symptoms, and possibly prevent the discontinuation or delay of cancer treatment in patients treated with capecitabine and similar drugs. These clinical advances would improve and prolong patient quality of life during cancer treatment and prevent complications that result in hospitalization.

Importance Insurance barriers to cancer care can cause significant patient and clinician burden. Objective To investigate the association of insurance denial with changes in technique, dose, and time to delivery of radiation oncology treatment. Design, Setting, and Participants In this single-institution cohort analysis, data were collected from patients with payer-denied authorization for radiation therapy (RT) from November 1, 2021, to December 8, 2022. Data were analyzed from December 15, 2022, to December 31, 2023. Exposure Insurance denial for RT. Main Outcomes and Measures Association of these denials with changes in RT technique, dose, and time to treatment delivery was assessed using chi(2) tests. Results A total of 206 cases (118 women [57.3%]; median age, 58 [range, 26-91] years) were identified. Most insurers (199 [96.6%]) were commercial payers, while 7 (3.4%) were Medicare or Medicare Advantage. One hundred sixty-one patients (78.2%) were younger than 65 years. Of 206 cases, 127 (61.7%) were ultimately authorized without any change to the requested RT technique or prescription dose; 56 (27.2%) were authorized after modification to RT technique and/or prescription dose required by the payer. Of 21 cases with required prescription dose change, the median decrease in dose was 24.0 (range, 2.3-51.0) Gy. Of 202 cases (98.1%) with RT delivered, 72 (34.9%) were delayed for a mean (SD) of 7.8 (9.1) days and median of 5 (range, 1-49) days. Four cases (1.9%) ultimately did not receive any authorization, with 3 (1.5%) not undergoing RT, and 1 (0.5%) seeking treatment at another institution. Conclusions and Relevance In this cohort study of patients with payer-denied cases, most insurance denials in radiation oncology were ultimately approved on appeal; however, RT technique and/or effectiveness may be compromised by payer-mandated changes. Further investigation and action to recognize the time and financial burdens on clinicians and clinical effects on patients caused by insurance denials of RT is needed.

Background: Electromagnetic transponders bronchoscopically implanted near the tumor can be used to monitor deep inspiration breath hold (DIBH) for thoracic radiation therapy (RT). The feasibility and safety of this approach require further study. Methods: We enrolled patients with primary lung cancer or lung metastases. Three transponders were implanted near the tumor, followed by simulation with DIBH, free breathing, and 4D-CT as backup. The initial gating window for treatment was ±5 mm; in a second cohort, the window was incrementally reduced to determine the smallest feasible gating window. The primary endpoint was feasibility, defined as completion of RT using transponder-guided DIBH. Patients were followed for assessment of transponder- and RT-related toxicity. Results: We enrolled 48 patients (35 with primary lung cancer and 13 with lung metastases). The median distance of transponders to tumor was 1.6 cm (IQR 0.6–2.8 cm). RT delivery ranged from 3 to 35 fractions. Transponder-guided DIBH was feasible in all but two patients (96% feasible), where it failed because the distance between the transponders and the antenna was >19 cm. Among the remaining 46 patients, 6 were treated prone to keep the transponders within 19 cm of the antenna, and 40 were treated supine. The smallest feasible gating window was identified as ±3 mm. Thirty-nine (85%) patients completed one year of follow-up. Toxicities at least possibly related to transponders or the implantation procedure were grade 2 in six patients (six incidences, cough and hemoptysis), grade 3 in three patients (five incidences, cough, dyspnea, pneumonia, and supraventricular tachycardia), and grade 4 pneumonia in one patient (occurring a few days after implantation but recovered fully and completed RT). Toxicities at least possibly related to RT were grade 2 in 18 patients (41 incidences, most commonly cough, fatigue, and pneumonitis) and grade 3 in four patients (seven incidences, most commonly pneumonia), and no patients had grade 4 or higher toxicity. Conclusions: Bronchoscopically implanted electromagnetic transponder–guided DIBH lung RT is feasible and safe, allowing for precise tumor targeting and reduced normal tissue exposure. Transponder–antenna distance was the most common challenge due to a limited antenna range, which could sometimes be circumvented by prone positioning.