Study of linear energy transfer effect on rib fracture in breast patients receiving pencil-beamscanning proton therapy.

Purpose: To study the effect of proton linear energy transfer (LET) on rib fracture in breast cancer patients treated with pencil-beam scanning proton therapy (PBS) using a novel tool of dose-LET volume histogram (DLVH). Methods: From a prospective registry of patients treated with post-mastectomy proton therapy to the chest wall and regional lymph nodes for breast cancer between 2015 and 2020, we retrospectively identified rib fracture cases detected after completing treatment. Contemporaneously treated control patients that did not develop rib fracture were matched to patients 2:1 considering prescription dose, boost location, reconstruction status, laterality, chest wall thickness, and treatment year.The DLVH index, V(d, l), defined as volume(V) of the structure with at least dose(d) and LET(l), was calculated. DLVH plots between the fracture and control group were compared. Conditional logistic regression (CLR) model was used to establish the relation of V(d, l) and the observed fracture at each combination of d and l. The p-value derived from CLR model shows the statistical difference between fracture patients and the matched control group. Using the 2D p-value map derived from CLR model, the DLVH features associated with the patient outcomes were extracted. Results: Seven rib fracture patients were identified, and fourteen matched patients were selected for the control group. The median time from the completion of proton therapy to rib fracture diagnosis was 12 months (range 5 to 14 months). Two patients had grade 2 symptomatic rib fracture while the remaining 5 were grade 1 incidentally detected on imaging. The derived p-value map demonstrated larger V(0-36Gy[RBE], 4.0-5.0 keV/µm) in patients experiencing fracture (p<0.1). For example, the p value for V(30 Gy[RBE], 4.0 keV/um) was 0.069. Conclusions: In breast cancer patients receiving PBS, a larger volume of chest wall receiving moderate dose and high LET may result in increased risk of rib fracture.

De-escalation of axillary surgery in patients outside Z0011 criteria.

Over the past 2 decades, axillary surgical management for breast cancer patients has been reshaped after several practice-changing randomized clinical trials provided evidence to support the de-escalation of axillary surgery, specifically the omission of axillary lymph node dissection, for patients with positive axillary lymph nodes. One such practice-changing trial was the American College of Surgeons Oncology Group Z0011 trial, which showed that patients with clinical T1-2 breast tumors and limited nodal disease (1-2 positive sentinel lymph nodes) who underwent upfront breast-conserving therapy could be safely spared the morbidity of axillary lymph node dissection. American College of Surgeons Oncology Group Z0011 has been criticized as several important groups were excluded, such as patients who underwent a mastectomy, patients with >2 positive sentinel lymph nodes, or patients with imaging-detected lymph node metastases. These exclusions have led to unclear guidelines and very difficult management decisions for many patients with breast cancer who are just outside the Z0011 criteria. Several subsequent trials that investigated sentinel lymph node biopsy alone or sentinel lymph node biopsy plus axillary radiation versus axillary lymph node dissection enrolled patients with higher volumes of disease than American College of Surgeons Oncology Group Z0011, such as mastectomy patients or patients with >2 positive sentinel lymph nodes. The goal of this review is to describe the findings of these trials and to discuss the current best practices regarding axillary management in patients who are candidates for upfront surgery but were excluded from American College of Surgeons Oncology Group Z0011, with a particular focus on patients undergoing mastectomy, patients with >2 positive sentinel lymph nodes, patients with large or multifocal tumors, and patients with imaging-detected biopsy-proven lymph node metastases.

Postmastectomy Intensity Modulated Proton Therapy: 5-Year Oncologic and Patient-Reported Outcomes.

PURPOSE: To report oncologic, physician-assessed, and patient-reported outcomes (PROs) for a group of women homogeneously treated with modern, skin-sparing multifield optimized pencil-beam scanning proton (intensity modulated proton therapy [IMPT]) postmastectomy radiation therapy (PMRT). METHODS AND MATERIALS: We reviewed consecutive patients who received unilateral, curative-intent, conventionally fractionated IMPT PMRT between 2015 and 2019. Strict constraints were applied to limit the dose to the skin and other organs at risk. Five-year oncologic outcomes were analyzed. Patient-reported outcomes were evaluated as part of a prospective registry at baseline, completion of PMRT, and 3 and 12 months after PMRT. RESULTS: A total of 127 patients were included. One hundred nine (86%) received chemotherapy, among whom 82 (65%) received neoadjuvant chemotherapy. The median follow-up was 4.1 years. Five-year locoregional control was 98.4% (95% CI, 93.6-99.6), and overall survival was 87.9% (95% CI, 78.7-96.5). Acute grade 2 and 3 dermatitis was seen in 45% and 4% of patients, respectively. Three patients (2%) experienced acute grade 3 infection, all of whom had breast reconstruction. Three late grade 3 adverse events occurred: morphea (n = 1), infection (n = 1), and seroma (n = 1). There were no cardiac or pulmonary adverse events. Among the 73 patients at risk for PMRT-associated reconstruction complications, 7 (10%) experienced reconstruction failure. Ninety-five patients (75%) enrolled in the prospective PRO registry. The only metrics to increase by >1 point were skin color (mean change: 5) and itchiness (2) at treatment completion and tightness/pulling/stretching (2) and skin color (2) at 12 months. There was no significant change in the following PROs: bleeding/leaking fluid, blistering, telangiectasia, lifting, arm extension, or bending/straightening the arm. CONCLUSIONS: With strict dose constraints to skin and organs at risk, postmastectomy IMPT was associated with excellent oncologic outcomes and PROs. Rates of skin, chest wall, and reconstruction complications compared favorably to previous proton and photon series. Postmastectomy IMPT warrants further investigation in a multi-institutional setting with careful attention to planning techniques.

Integrating a Grassroots Well-Being Curriculum into a Radiation Oncology Residency Program.

PURPOSE: The burnout rate among US radiation oncology residents was 33% in 2016. To our knowledge there are no published interventions addressing burnout among radiation oncology residents. We describe the implementation of a well-being curriculum, cocreated by a psychologist, a medical humanities professional, and radiation oncology attending and resident physicians. METHODS AND MATERIALS: Radiation oncology residents at our institution were surveyed to determine themes that induced burnout. A curriculum was developed, with monthly small group sessions focused on 1 identified topic. Sessions alternated between psychological tool-focused approaches and humanities exercises. These were led by a psychologist or medical humanities professional. Residents were given protected time to attend sessions during business hours. Participation was optional. Participants were assigned a random identifier, and the Stanford Professional Fulfillment Index (PFI) was assessed at baseline and 3-month intervals. PFI trends were analyzed after 1 year. At the end of the year, a focus group was held to evaluate work satisfaction and self-reported interactions with patients and coworkers. This information was used to improve the curriculum. RESULTS: All 12 residents in the radiation oncology program participated in the curriculum. There was an equal number of residents of postgraduate years 2 through 5. Six of the participants were female. Of the participants, 11 completed the PFI. At baseline, 80% of residents met criteria for burnout. This decreased to 67%, 50%, and 33% at 3, 6, and 9 months, respectively. The proportion of residents meeting criteria for very good professional fulfillment was 30%, 56%, 38%, and 22% at baseline and 3, 6, and 9 months, respectively. On average, 9 of 12 residents attended each session. CONCLUSIONS: Our experience demonstrates the feasibility of collaborating with residents in the development of a well-being curriculum to cater programming to their needs, which we believe led to excellent engagement and attendance at each session.

Liver Metastasis-Directed Ablative Radiotherapy in Pancreatic Cancer Offers Prolonged Time Off Systemic Therapy in Selected Patients: Data From a Multi-institutional Retrospective Study.

OBJECTIVES: We evaluated the outcomes of metastatic pancreatic cancer (MPC) patients who underwent liver metastases (LMs)-directed ablative radiotherapy (RT) and sought to characterize patients with more favorable prognosis. METHODS: A retrospective analysis of 76 MPC patients who underwent ablative RT (median dose, 50 Gy) to LM at 3 academic centers between 2008 and 2018 was performed. Endpoints were local control (LC), progression-free survival, and overall survival (OS) since RT. RESULTS: Median follow-up was 10.9 months. Liver metastases were metachronous in 68%. Before RT, LM was responsive/stable on chemotherapy (CTX) in 36% whereas progressive in 43%. Median carbohydrate antigen 19-9 (CA 19-9) at RT was 334 U/mL. After RT, 32% had ≥6 months of CTX break. Twelve-month outcomes were: LC, 66%; progression-free survival, 7%; and OS, 38%. On multivariable analysis, Eastern Cooperative Oncology Group 2-3 (hazard ratio [HR], 13.49; P < 0.01), progressive LM on CTX (HR, 3.26; P < 0.01), and higher CA 19-9 (log10 scale; HR, 1.39; P < 0.01) at RT predicted worse OS. CONCLUSIONS: Ablative RT to LM in setting of MPC may offer LC of systemic disease and thus quality time off CTX. Selected patients with good performance status, stable/responsive LM on CTX, and lower CA 19-9 have more favorable prognosis.

Ablative radiotherapy for ultracentral lung cancers: Dosimetric, geometric, and volumetric predictors of outcomes and toxicity.

BACKGROUND: Ultracentral lung cancers arise near the proximal bronchial tree (PBT), trachea, or esophagus, and have been associated with worse outcomes and increased toxicity after radiotherapy. We sought to associate dosimetric and anatomic factors with oncologic outcomes and toxicities. METHODS: One-hundred ten patients treated with ablative, curative-intent radiotherapy for ultracentral, node-negative, non-small cell lung cancer were included. Dosimetric and geometric data obtained using custom software that calculated volumes of target structures and organs-at-risk and measured the shortest vector length between these volumes were associated with outcomes and toxicity. RESULTS: Common dose/fractionation schemes included 50 Gy in 5 fractions (57%), 60 Gy in 8 fractions (15%), and 48 Gy in 4 fractions (13%). Overall survival at 1, 2, and 5 years was 78%, 57%, and 32%, respectively. Factors significantly associated with death included endobronchial tumor, gross tumor volume (GTV) or planning target volume (PTV) contacting PBT, shorter distance from GTV to PBT or esophagus, volume of PBT receiving prescription dose, higher pericardium max dose, lung V20Gy, and mean lung dose. Local progression at 1, 2, and 5 years was 4%, 16%, and 21%. Factors associated with local progression were lower GTV minimum dose and higher GTV/PTV volume ratio. Acute and late grade 2 + toxicity was seen in 18% and 27%, respectively. Four patients (4%) had fatal toxicity. CONCLUSIONS: Lower GTV minimum dose and smaller volumetric PTV expansions may increase risk of local progression, and should be balanced against normal tissue doses including pericardium maximum dose, lung V20Gy, and mean lung dose.

Proton beam radiotherapy for esophagus cancer: state of the art.

The majority of esophageal cancer patients are diagnosed with locoregionally confined disease, which is often amenable to curative intent therapy. Chemoradiotherapy (CRT) improves overall survival (OS) in stage II and III esophagus cancer in the neoadjuvant and definitive settings. Due to the close proximity of organs at risk (OARs), including lungs, heart, stomach, bowel, kidneys, and spinal cord, esophageal CRT can result in profound acute and late toxicities. Acute toxicities can include esophagitis, nausea, vomiting, fatigue, and cytopenias. Late complications may also occur months or years after completion of thoracic radiotherapy, including significant cardiac, pulmonary, liver, kidney, or bowel toxicities, which can be life-threatening or fatal. Photon-based radiotherapy exposes OARs to significant doses of radiation, whereas proton beam therapy (PBT) has unique physical properties, as it lacks an exit dose. This allows PBT to deliver, a more conformal dose to the target and minimize the volume of OARs exposed to radiation. This dosimetric advantage may portend an increased therapeutic ratio of CRT for esophagus cancer. The objective of this review is to discuss the evolution of photon and proton-based radiotherapy techniques, rationale, dosimetric and clinical studies comparing outcomes of photon- and proton-based techniques, ongoing prospective trials, and future directions of PBT as a means of reducing toxicity and improving oncologic outcomes for patients with esophagus cancer.

Comparing bowel and urinary domains of patient-reported quality of life at the end of and 3 months post radiotherapy between intensity-modulated radiotherapy and proton beam therapy for clinically localized prostate cancer.

PURPOSE: To prospectively assess acute differences in patient-reported outcomes in bowel and urinary domains between intensity-modulated radiotherapy (IMRT) and proton beam therapy (PBT) for prostate cancer. METHODS AND MATERIALS: Bowel function (BF), urinary irritative/obstructive symptoms (UO), and urinary incontinence (UI) domains of EPIC-26 were collected in patients with T1-T2 prostate cancer receiving IMRT or PBT at a tertiary cancer center (2015-2018). Mean changes in domain scores were analyzed from pretreatment to the end of and 3 months post-radiotherapy for each modality. A clinically meaningful change was defined as a score change >50% of the baseline standard deviation. RESULTS: A total of 157 patients receiving IMRT and 105 receiving PBT were included. There were no baseline differences in domain scores between cohorts. At the end of radiotherapy, there was significant and clinically meaningful worsening of BF and UO scores for patients receiving either modality. In the BF domain, the IMRT cohort experienced greater decrement (-13.0 vs -6.7, P < .01), and had a higher proportion of patients with clinically meaningful reduction (58.4% vs 39.5%, P = .01), compared to PBT. At 3 months post-radiotherapy, the IMRT group had significant and clinically meaningful worsening of BF (-9.3, P < .001), whereas the change in BF score of the PBT cohort was no longer significant or clinically meaningful (-1.2, P = .25). There were no significant or clinically meaningful changes in UO or UI 3 months post-radiotherapy. CONCLUSIONS: PBT had less acute decrement in BF than IMRT following radiotherapy. There was no difference between the two modalities in UO and UI.

Outcomes and Profiles of Older Patients Receiving Definitive Radiation Therapy for Muscle-Invasive Bladder Cancer at a Tertiary Medical Center.

PURPOSE: Our purpose was to evaluate the outcomes and profiles of older patients with muscle-invasive bladder cancer (MIBC) treated with definitive radiation therapy (RT) with or without chemotherapy (CHT) at a tertiary medical center. METHODS AND MATERIALS: A retrospective study was conducted for older patients with MIBC who were ≥70 years old and underwent RT with or without CHT between 2000 and 2016. Overall survival (OS) was estimated using the Kaplan-Meier method. Disease-specific survival (DSS), cumulative incidence of progression, patterns of recurrence, and toxicities were examined. Univariate analyses were performed to identify variables associated with OS, DSS, and cumulative incidence of progression, using the Cox proportional hazards model. RESULTS: A total of 84 patients underwent definitive RT with or without CHT. Of these, only 29% were deemed medically fit to undergo radical cystectomy, and the remainder were medically unfit or had surgically unresectable disease. Median age was 81 years. Sixty-one percent, 29%, and 11% had clinical stage II, III, and IV disease, respectively. Eighty-six percent had maximal transurethral resection of bladder tumor before RT. Seventy-three percent received CHT with RT, and 27% had RT alone. Median follow-up was 5.7 years. Median OS was 1.9 years. OS was 42% and 25%, and DSS was 64% and 54% at 3 and 5 years, respectively. On univariate analysis, medical fitness to undergo radical cystectomy, receipt of CHT, lower T stage, and maximal transurethral resection of bladder tumor were associated with better OS; lower T stage was associated with better DSS. The cumulative incidence of progression was 44% and 49% at 3 and 5 years, respectively. Late grade 3 genitourinary and gastrointestinal toxicity were 15% and 4%, respectively. None had grade 4 or 5 toxicity. CONCLUSIONS: Older patients with MIBC referred for RT were often medically unfit or had a surgically unresectable tumor. In these medically compromised patients, definitive RT with or without CHT was well tolerated and yielded encouraging treatment outcomes.

Isolated biopsy-proven recurrence of prostate carcinoma in the spermatic cord after radical prostatectomy detected with 11C-Choline PET/CT.

We report an unusual case of a solitary prostatic metastasis in the spermatic cord, following robotic-assisted laparoscopic radical prostatectomy with pelvic lymph node dissection and salvage radiotherapy, detected with the use of 11C-Choline PET/CT, heralded by a progressive rise in PSA. This lesion was biopsy-proven and surgically resected through radical left-sided orchiectomy. Postoperatively his PSA was undetectable and remained undetectable with no evidence of recurrent disease.