Clinical Physics Boot Camp for Radiation Oncology Residents: A Pilot Study.

The physics curriculum is a source of anxiety both for medical students considering radiation oncology (RO) as a possible career and for current residents facing the physics boards. To improve the orientation process for residents and medical students, we created a physics boot camp using clinically relevant patient vignettes to teach physics fundamentals. The initial boot camp was a week-long program of 1.5 to 2 hours daily, with each day consisting of a didactic session and hands-on laboratory. Boot camp topics covered included physics fundamentals, electron treatments, photon treatments, brachytherapy, and urgent clinical setups. Learners completed pre- and postsurveys, where each rated their knowledge and comfort level with RO workflow on a 5-point scale. Learners also completed daily knowledge-based assessments testing the information presented before and after these daily sessions. A total of 10 participants were included in the initial boot camp: 8 residents and 2 medical students. A repeat, single-day, multi-institutional boot camp a year later included 5 of the original resident participants. Participant scores were paired for analysis using student t tests. For the initial boot camp, all participants reported significantly increased confidence in the physics aspects of the RO workflow (mean 3.24 vs 4.18; P = .0023). However, when comparing those self-assessment scores from participants with more than a year of physics background to those earlier in their training, only the early training participants' scores remained significant (advanced learners: mean 4.0 vs 4.38, P = .129; early learners: mean 2.66 vs 4.02, P = .0025). All participants had improved scores on their knowledge-based assessments (mean 74% vs 89%; P = .0001), which remained statistically significant for both early learners (mean 68% vs 87%; P = .0005) and advanced learners (mean 84% vs 93%; P = .0447). For repeat participants, preboot camp knowledge showed continued improvement (mean 61% vs 79%; P = .049) at 1 year. A formal physics boot camp orientation improves both resident comfort level and knowledge base with clinical physics, with participants early in their training deriving the greatest benefit.

Long-Term Adherence to Adjuvant Endocrine Therapy Following Various Radiotherapy Modalities in Early Stage Hormone Receptor Positive Breast Cancer.

INTRODUCTION: We compared the rates of long-term adjuvant endocrine therapy (AET) adherence after various radiation therapy (RT) modalities among patients with early stage breast cancer. MATERIALS AND METHODS: Medical records from patients with stage 0, I, or IIA (tumors ≤3 cm), hormone receptor (HR) positive breast cancer that received adjuvant radiation therapy (RT) from 2013 to 2015 at a single institution were retrospectively reviewed. All patients received breast conserving surgery (BCS) followed by adjuvant RT via one of the following modalities: whole breast radiotherapy (WBI), partial breast irradiation (PBI) with either external beam radiation therapy (EBRT) or fractionated intracavitary high-dose rate (HDR) brachytherapy, or single fraction HDR-brachytherapy intraoperative-radiation therapy (IORT). RESULTS: One hundred fourteen patients were reviewed. Thirty patients received WBI, 41 PBI, and 43 IORT with a median follow up of 64.2, 72.0, and 58.6 months, respectively. For the entire cohort, AET adherence was approximately 64% at 2 years and 56% at 5 years. Among patients in the IORT clinical trial, adherence to AET was approximately 51% at 2 years and 40% at 5 years. After controlling for additional factors, DCIS histology (vs invasive disease) and IORT (compared to other radiation modalities) were associated with decreased endocrine therapy adherence (P < 0.05). CONCLUSION: DCIS histology and receipt of IORT were associated with lower rates of adherence to AET at 5 years. Our findings suggest that examination of the efficacy of RT interventions such as PBI and IORT in patients who do not receive AET is warranted.

Radiotherapy Induces Innate Immune Responses in Patients Treated for Prostate Cancers.

PURPOSE: Radiotherapy is a curative therapeutic modality used to treat cancers as a single agent or in combination with surgery and chemotherapy. Advanced radiotherapy technologies enable treatment with large fractions and highly conformal radiation doses to effect free-radical damage to cellular DNA leading to cell-cycle arrest, cell death, and innate immune response (IIR) stimulation. EXPERIMENTAL DESIGN: To understand systemic clinical responses after radiation exposure, proteomic and metabolomic analyses were performed on plasma obtained from patients with cancer at intervals after prostate stereotactic body radiotherapy. Pathway and multivariate analyses were used to delineate molecular alterations following radiotherapy and its correlation with clinical outcomes. RESULTS: DNA damage response increased within the first hour after treatment and returned to baseline by 1 month. IIR signaling also increased within 1 hour of treatment but persisted for up to 3 months thereafter. Furthermore, robust IIR and metabolite elevations, consistent with an early proinflammatory M1-mediated innate immune activation, were observed in patients in remission, whereas patients experiencing prostate serum antigen-determined disease progression demonstrated less robust immune responses and M2-mediated metabolite elevations. CONCLUSIONS: To our knowledge, these data are the first report of longitudinal proteomic and metabolomic molecular responses in patients after radiotherapy for cancers. The data supports innate immune activation as a critical clinical response of patients receiving radiotherapy for prostate cancer. Furthermore, we propose that the observed IIR may be generalized to the treatment of other cancer types, potentially informing multidisciplinary therapeutic strategies for cancer treatment.

A comparative study using time-driven activity-based costing in single-fraction breast high-dose rate brachytherapy: An integrated brachytherapy suite vs. decentralized workflow.

INTRODUCTION: Precision breast intraoperative radiation therapy (PB-IORT) is a novel approach to adjuvant radiation therapy for early-stage breast cancer performed as part of a phase II clinical trial at two institutions. One institution performs the entire procedure in an integrated brachytherapy suite which contains a CT-on-rails imaging unit and full anesthesia capabilities. At the other, breast conserving surgery and radiation therapy take place in two separate locations. Here, we utilize time-driven activity-based costing (TDABC) to compare these two models for the delivery of PB-IORT. METHODS: Process maps were created to describe each step required to deliver PB-IORT at each institution, including personnel, equipment, and supplies. Time investment was estimated for each step. The capacity cost rate was determined for each resource, and total costs of care were then calculated by multiplying the capacity cost rates by the time estimate for the process step and adding any additional product costs. RESULTS: PB-IORT costs less to deliver at a distributed facility, as is more commonly available, than an integrated brachytherapy suite ($3,262.22 vs. $3,996.01). The largest source of costs in both settings ($2,400) was consumable supplies, including the brachytherapy balloon applicator. The difference in costs for the two facility types was driven by personnel costs ($1,263.41 vs. $764.89). In the integrated facility, increased time required by radiation oncology nursing and the anesthesia attending translated to the greatest increases in cost. Equipment costs were also slightly higher in the integrated suite setting ($332.60 vs. $97.33). CONCLUSIONS: The overall cost of care is higher when utilizing an integrated brachytherapy suite to deliver PB-IORT. This was primarily driven by additional personnel costs from nursing and anesthesia, although the greatest cost of delivery in both settings was the disposable brachytherapy applicator. These differences in cost must be balanced against the potential impact on patient experience with these approaches.

Time-driven activity-based costing of a novel form of CT-guided high-dose-rate brachytherapy intraoperative radiation therapy compared with conventional breast intraoperative radiation therapy for early stage breast cancer.

INTRODUCTION: Intraoperative radiation therapy is an emerging option for adjuvant therapy for early stage breast cancer, although it is not currently considered standard of care in the United States. We applied time-driven activity-based costing to compare two alternative methods of breast intraoperative radiation therapy, including treatment similar to the techniques employed in the TARGIT-A clinical trial and a novel version with CT-guidance and high-dose-rate (HRD) brachytherapy. METHODS AND MATERIALS: Process maps were created to describe the steps required to deliver intraoperative radiation therapy for early stage breast cancer at each institution. The components of intraoperative radiation therapy included personnel, equipment, and consumable supplies. The capacity cost rate was determined for each resource. Based on this, the delivery costs were calculated for each regimen. For comparison across centers, we did not account for indirect facilities costs and interinstitutional differences in personnel salaries. RESULTS: The CT-guided, HRD form of intraoperative radiation therapy costs more to deliver ($4,126.21) than the conventional method studied in the TARGIT-A trial ($1,070.45). The cost of the brachytherapy balloon applicator ($2,750) was the primary driver of the estimated differences in costs. Consumable supplies were the largest contributor to the brachytherapy-based approach, whereas personnel costs were the largest contributor to costs of the standard form of intraoperative radiation therapy. CONCLUSIONS: When compared with the more established method of intraoperative radiation therapy using a portable superficial photon unit, the delivery of treatment with CT guidance and HDR brachytherapy is associated with substantially higher costs. The excess costs are driven primarily by the cost of the disposable brachytherapy balloon applicator and, to a lesser extent, additional personnel costs. Future work should include evaluation of a less expensive brachytherapy applicator to increase the anticipated value of brachytherapy-based intraoperative radiation therapy.

Pathologic Evaluation and Prognostic Implications of Nodal Micrometastases in Breast Cancer.

Using modern sentinel lymph node techniques, occult nodal metastases including micrometastases or isolated tumor cells are being increasingly discovered in up to 10% of early-stage breast cancers. Furthermore, the rate of nonsentinel lymph node involvement is approximately 10%. However, the impact of these findings on disease-free survival is low, particularly with regards to axillary recurrences. Current evidence suggests small-volume lymph node involvement in breast cancer patients is only one of several factors that should guide adjuvant therapy options. In otherwise favorable patients, adjuvant radiation and systemic therapy can help mitigate the risk of recurrence when omitting axillary lymph node dissection.

Squamous cell carcinoma of the rectum: Practice trends and patient survival.

PURPOSE: Leverage the National Cancer Database (NCDB) to evaluate trends in management of nonmetastatic squamous cell cancer (SCC) of the rectum and their effect on survival for this uncommon tumor. METHODS AND MATERIALS: Retrospective data was obtained from the NCDB for patients diagnosed with SCC of the rectum between 2004 and 2014, including cT1-4, cN0-2, cM0 tumors (cohort A, n = 2296). A subgroup analysis was performed on locally advanced tumors (cT1-T2, N+ or cT3, N any, subcohort B, n = 883), treated with chemoradiation (n = 706) or trimodality therapy (n = 177) including chemotherapy, radiation, and surgery. Pathological complete response rate following neoadjuvant therapy was obtained. Univariate and multivariate logistic regression analyses were performed to generate hazard ratios (HR) investigating factors associated with overall survival. Kaplan-Meier (K-M) method was used to estimate overall surviving proportion at 5 and 10 years. RESULTS: The K-M estimated 5 and 10 year overall survival for stage I disease was 71.3% and 57.8%, respectively; stage II disease was 57.0% and 38.9%, respectively; stage III disease was 57.8% and 41.5%, respectively. On multivariate analysis, higher cT category (P < 0.001) resulted in worse survival. For locally advanced tumors (subcohort B), there was no significant difference in survival between chemoradiation alone compared to trimodality therapy (P = 0.909 on multivariate analysis). CONCLUSIONS: Most providers manage locally advanced SCC of the rectum similar to anal cancer, which results in equivalent overall survival and spares patients from the additional morbidity associated with surgical resection.

Short-course Versus Long-course Neoadjuvant Therapy for Non-metastatic Rectal Cancer: Patterns of Care and Outcomes From the National Cancer Database.

INTRODUCTION: The purpose of this study was to compare the utilization, pathologic response, and overall survival (OS) between long-course neoadjuvant chemoradiation (LC-CRT) and short-course neoadjuvant radiation (SC-RT) in the treatment of non-metastatic rectal cancer. METHODS AND MATERIALS: Retrospective data was obtained from the National Cancer Database (NCDB) for patients diagnosed with clinical stage II or III (limited to T3, any N or T1-2, N1-2) rectal cancer between 2004 and 2014 (28,193 patients). Univariate and multivariate analyses were performed to investigate factors associated with receipt of SC-RT, pathologic complete response (pCR) rate, and OS. Patients were compared based on the neoadjuvant therapy they received prior to tumor resection. SC-RT was defined as 25 Gy given over 1 week prior to surgery (with or without chemotherapy as part of their treatment course). LC-CRT was defined as 45 to 60 Gy given over 5 to 6 weeks (with chemotherapy) prior to surgery. RESULTS: A total of 27,988 (99%) of patients received LC-CRT, and 205 (1%) patients received SC-RT. Receipt of SC-RT was associated with older age, more comorbidities, and treatment at an academic facility (P < .001 for each). Additional days from radiation completion to surgery was associated with a higher pCR rate (P < .001 for both). LC-CRT did not lead to increased OS compared with SC-RT (P = .517). CONCLUSIONS: In this United States database study, there was no improvement in OS for patients receiving LC-CRT compared with SC-RT; however, a longer interval between radiation therapy and surgery led to a higher pCR rate. Academic facilities were more likely to utilize SC-RT compared with other facilities.

The Effect of Receptor Status on Mastectomy and Contralateral Prophylactic Mastectomy Rates in Early Stage Invasive Breast Carcinoma.

BACKGROUND: There is an established relationship between hormone receptor (HR; estrogen and/or progesterone receptors) status, HER2 status, and locoregional recurrence. The purpose of this study was to analyze how HR and HER2 receptor status have influenced the surgical management trends among patients with early stage breast cancer. PATIENTS AND METHODS: The National Cancer Database was queried for patients with cT1 to cT3, cN0, and cM0 breast carcinoma from 2004 to 2012. Patients were grouped on the basis of receptor status and surgical management (mastectomy or breast-conserving surgery [BCS]). Multivariable analyses were performed to investigate factors associated with increased odds of receiving mastectomy over BCS. Among a subgroup of patients who underwent ipsilateral mastectomy, analyses were performed to determine any association between contralateral prophylactic mastectomy (CPM) and receptor status. RESULTS: We found 280,241 patients who met inclusion criteria for analyzing mastectomy or BCS surgical decision. Patients with HER2-positive (HER2+) tumors (HR+/HER+ and HR-/HER2+) were the most likely to undergo mastectomy (odds ratio [OR], 1.212 and 1.499 respectively, compared with HR+/HER2- patients, each P < .001). HR status alone did not affect ipsilateral surgical management as patients with HR+/HER2- and HR-/HER2- tumors demonstrated similar mastectomy rates (P = .391). Among the 108,018 who underwent mastectomy, 20% underwent CPM. After adjustment, patients with HR+/HER2+, HR-/HER2+, and HR-/HER2- were all more likely to undergo CPM (OR 1.356, 1.608, and 1.358, respectively compared with HR+/HER2- patients, each P < .001). CONCLUSION: This analysis indicates that patients with early stage breast cancer are more likely to undergo a mastectomy and CPM if they have HER2+ tumors.

Dysuria Following Stereotactic Body Radiation Therapy for Prostate Cancer.

BACKGROUND: Dysuria following prostate radiation therapy is a common toxicity that adversely affects patients' quality of life and may be difficult to manage. METHODS: Two hundred four patients treated with stereotactic body radiation therapy (SBRT) from 2007 to 2010 for localized prostate carcinoma with a minimum follow-up of 3 years were included in this retrospective review of prospectively collected data. All patients were treated to 35-36.25 Gy in five fractions delivered with robotic SBRT with real time fiducial tracking. Dysuria and other lower urinary tract symptoms were assessed via Question 4b (Pain or burning on urination) of the expanded prostate index composite-26 and the American Urological Association (AUA) Symptom Score at baseline and at routine follow-up. RESULTS: Two hundred four patients (82 low-, 105 intermediate-, and 17 high-risk according to the D'Amico classification) at a median age of 69 years (range 48-91) received SBRT for their localized prostate cancer with a median follow-up of 47 months. Bother associated with dysuria significantly increased from a baseline of 12% to a maximum of 43% at 1 month (p < 0.0001). There were two distinct peaks of moderate to severe dysuria bother at 1 month and at 6-12 months, with 9% of patients experiencing a late transient dysuria flare. While a low level of dysuria was seen through the first 2 years of follow-up, it returned to below baseline by 2 years (p = 0.91). The median baseline AUA score of 7.5 significantly increased to 11 at 1 month (p < 0.0001) and returned to 7 at 3 months (p = 0.54). Patients with dysuria had a statistically higher AUA score at baseline and at all follow-ups up to 30 months. Dysuria significantly correlated with dose and AUA score on multivariate analysis. Frequency and strain significantly correlated with dysuria on stepwise multivariate analysis. CONCLUSION: The rate and severity of dysuria following SBRT is comparable to patients treated with other radiation modalities.