Achieving the Unachievable: Work-Life Balance in Radiation Oncology.

As radiation oncologists, we often participate in discussions on work-life balance, are offered lectures and free meals, and complete hospital-mandated modules, all under the guise of physician wellness. But how often are these measures efficacious? How do we define being well in our demanding and fast-paced careers? What does it actually look like on a day-to-day basis to achieve work-life balance? Furthermore, is it even possible?

Bone marrow sparing in prostate cancer patients treated with Post-operative pelvic nodal radiotherapy - A proton versus photon comparison.

PURPOSE: Extending salvage radiotherapy to treat the pelvic lymph nodes (PLNRT) improves oncologic outcomes in prostate cancer (PCa). However, a larger treatment volume increases the extent of bone marrow (BM) exposure, which is associated with hematologic toxicity (HT). Given the potential long-term impact of BM dose in PCa, clinical studies on BM sparing (BMS) are warranted. Herein, we dosimetrically compared photon and proton plans for BMS. MATERIALS AND METHODS: Treatment plans of 20 post-operative PCa patients treated with volumetric-modulated arc photon therapy (VMAT) PLNRT were retrospectively identified. Contours were added for the whole pelvis BM (WPBM) and BM sub-volumes: lumbar-sacral (LSBM), iliac (ILBM), and lower pelvis (LPBM). Three additional plans were created: VMAT_BMS, intensity-modulated proton therapy (IMPT), and IMPT_BMS. Normal tissue complication probabilities (NTCP) for grade >3 hematologic toxicity (HT3+) were calculated for the WPBM volumes. RESULTS: Compared to the original VMAT plan, mean doses to all BM sub-volumes were statistically significantly lower for VMAT_BMS, IMPT, and IMPT_BMS resulting in average NTCP percentages of 20.5 ± 5.9, 10.7 ± 4.2, 6.1 ± 2.0, and 2.5 ± 0.6, respectively. IMPT_BMS had significantly lower low dose metrics (V300cGy-V2000cGy) for WPBM and sub-volumes except for LPBM V2000cGy compared to VMAT_BMS and ILBM V20Gy compared to IMPT. In most cases, V4000cGy and V5000cGy within ILBM and LSBM were significantly higher for IMPT plans compared to VMAT plans. CONCLUSIONS: BMS plans are achievable with VMAT and IMPT without compromising target coverage or OARs constraints. IMPT plans were overall better at reducing mean and NTCP for HT3+ as well as low dose volumes to BM. However, IMPT had larger high dose volumes within LSBM and ILBM. Further studies are warranted to evaluate the clinical implications of these findings.

CivaSheet® use for soft tissue sarcoma: A single institution experience.

OBJECTIVE: CivaSheet is a palladium-103, implantable, intraoperative radiation therapy device which emits unidirectional radiation that enables boost doses in patients who have otherwise received the maximum radiation dose. Here, we present our initial clinical experience with the first 10 cases using this new technology. METHODS AND MATERIALS: A retrospective chart review of all patients with STS treated with surgical resection and CivaSheet placement at the University of Miami Hospital, a tertiary care center, from January 2018 to December 2019, was performed. Adjuvant radiation was administered by a palladium-103 implant, which delivered an average of 47 Gy (35-55) to a depth of 5 mm. RESULTS: Nine patients underwent CivaSheet placement from January 2018 until December 2019 for a total of 10 CivaSheets placed (1 patient had 2 CivaSheets inserted) and followed for a mean of 27 months (4-45 months). Four tumors were located in the retroperitoneum, two in the chest, two in the groin, and two within the lower extremity. At the time of tumor resection and CivaSheet placement, tumor sizes ranged from 2.5 cm to 13.8 cm with an average of 7.6 cm. Four patients necessitated musculocutaneous tissue flaps for closure and reconstruction. All patients with Grade 4 complications had flap reconstruction and prior radiation. Four patients' tumors recurred locally for a local recurrence rate of 40%. Three patients had modified accordion Grade 4 complications necessitating additional surgery for CivaSheet removal. Extremity tumors unanimously developed modified accordion Grade 4 adverse events. CONCLUSIONS: CivaSheet may be an acceptable alternative treatment modality compared to prior brachytherapy methods.

Comprehensive genomic profiling and treatment patterns across ancestries in advanced prostate cancer: a large-scale retrospective analysis.

BACKGROUND: Men of African ancestry experience the greatest burden of prostate cancer globally, but they are under-represented in genomic and precision medicine studies. Therefore, we sought to characterise the genomic landscape, comprehensive genomic profiling (CGP) utilisation patterns, and treatment patterns across ancestries in a large, diverse, advanced prostate cancer cohort, to determine the impact of genomics on ancestral disparities. METHODS: In this large-scale retrospective analysis, the CGP-based genomic landscape was evaluated in biopsy sections from 11 741 patients with prostate cancer, with ancestry inferred using a single nucleotide polymorphism-based approach. Admixture-derived ancestry fractions for each patient were also interrogated. Independently, clinical and treatment information was retrospectively reviewed for 1234 patients in a de-identified US-based clinicogenomic database. Prevalence of gene alterations, including actionable gene alterations, was assessed across ancestries (n=11 741). Furthermore, real-world treatment patterns and overall survival was assessed in the subset of patients with linked clincogenomic information (n=1234). FINDINGS: The CGP cohort included 1422 (12%) men of African ancestry and 9244 (79%) men of European ancestry; the clinicogenomic database cohort included 130 (11%) men of African ancestry and 1017 (82%) men of European ancestry. Men of African ancestry received more lines of therapy before CGP than men of European ancestry (median of two lines [IQR 0-8] vs one line [0-10], p=0·029). In genomic analyses, ancestry-specific mutational landscapes were observed, but the prevalence of alterations in AR, the DNA damage response pathway, and other actionable genes were similar across ancestries. Similar genomic landscapes were observed in analyses that accounted for admixture-derived ancestry fractions. After undergoing CGP, men of African ancestry were less likely to receive a clinical study drug compared with men of European ancestry (12 [10%] of 118 vs 246 [26%] of 938, p=0·0005). INTERPRETATION: Similar rates of gene alterations with therapy implications suggest that differences in actionable genes (including AR and DNA damage response pathway genes) might not be a main driver of disparities across ancestries in advanced prostate cancer. Later CGP utilisation and a lower rate of clinical trial enrolment observed in men of African ancestry could affect genomics, outcomes, and disparities. FUNDING: American Society for Radiation Oncology, Department of Defense, Flatiron Health, Foundation Medicine, Prostate Cancer Foundation, and Sylvester Comprehensive Cancer Center.

WeWhoCurie: An Initiative to Advocate for Those Underrepresented in Radiation Oncology.

Purpose: An initiative to advocate for those underrepresented in radiation oncology. Methods and Materials: Inspired by the success of the #ILookLikeAnEngineer and #ILookLikeASurgeon campaigns, this initiative aimed to break down stereotypes in traditionally male-dominated fields. In honor of Marie Curie's birthday, on November 7, 2018, the Society for Women in Radiation Oncology launched a social media campaign called #WomenWhoCurie day. However, as the popularity of the social media campaign increased, it become evident that members of the wider radiation community, in particular women of color, nonbinary and transgender people did not feel supported by the #WomenWhoCurie movement. In November 2021, after consultation with diversity and inclusion leaders and members of other national radiation oncology organizations, Society for Women in Radiation Oncology launched #WeWhoCurie alongside the #WomenWhoCurie campaign for women and gender minorities in radiation oncology. Radiation oncologists, physicists, dosimetrist, therapists, nurses, and other professionals from around the world gathered and shared photos and social media posts throughout the day on multiple platforms including Facebook, Instagram, and Twitter. Results: In the year #WeWhoCurie, #WomenWhoCurie, #_______ WhoCurie campaign launched, we saw an increase in participation across the globe from 9 countries: the United States, Canada, Mexico, Brazil, Italy, Spain, China, New Zealand, and Australia. There were over 720 tweets contributing to the campaign with over 2000 messages, representing 3,365,444 "potential impacts", or the number of times someone saw the hashtag. Conclusions: Through this campaign we aim to celebrate the incredible women, gender minorities, and allies who are "Curie-ing" patients with cancer and conducting cutting edge research to improve cancer care across the globe. As an organization we believe adding our voices to the masses will foster a culture of inclusion for everyone. Afterall, what good is the practice of radiation oncology if all are not equally welcome?

Localized prostate cancer disparities in risk group at presentation and access to treatment for Hispanic men.

BACKGROUND: Despite great heterogeneity amongst Hispanic groups, prostate cancer studies often report Hispanic patients in aggregate. We sought to identify differences in prostate cancer risk group at presentation and treatment status among Hispanic subgroup populations. METHODS: Patients with localized prostate adenocarcinoma diagnosed from 2004-2017 were identified in the National Cancer Database (NCDB) and disaggregated by racial subgroup and Hispanic country of origin. Ordinal logistic regression defined adjusted odds ratios (AORs) with 95% CI of (1) presenting at progressively higher risk group and (2) receiving treatment with intermediate-unfavorable or high-risk disease. RESULTS: In our sample (n = 895,087), Hispanic men had greater odds of presenting with higher-risk localized prostate cancer compared with non-Hispanic White men (AOR = 1.18 95% CI 1.16-1.21, p < 0.001). Additionally, Hispanic Black men were less likely to present with higher-risk disease than non-Hispanic Black men. Disparities also existed when disaggregated by country of origin, particularly for Mexican men. Amongst men with unfavorable-risk disease, Hispanic men were less likely to receive treatment than non-Hispanic White men (95% CI 0.57-0.67, p < 0.001). The odds of Hispanic Black patients receiving treatment was 2.00 times the odds (95% CI 1.17-3.41 p = 0.011) of non-Hispanic Black patients receiving treatment. Upon disaggregation by country of origin, disparities persisted, particularly for Mexican men. CONCLUSION: We found marked heterogeneity when risk group at presentation and treatment for higher-risk disease were disaggregated by racial subgroup and country of origin. Our findings support further collection of disaggregated data in Hispanic communities and study of potential mechanisms underlying the observed differences.

Chromosome 8q arm overexpression is associated with worse prostate cancer prognosis.

OBJECTIVE: Chromosome 8q arm (chr8q) is the most amplified chromosomal segment in advanced metastatic castration-resistant prostate cancer after chXq12. These regions harbor important oncogenes driving prostate cancer progression, including MYC that plays a role in various hallmarks of cancer, including cell cycle progression and immune surveillance. Herein we characterize the co-expression patterns of chr8q genes and their clinical utility in more than 7,000 radical prostatectomy samples. MATERIALS AND METHODS: Copy Number alterations of 336 genes on chr8q21 to chr8q24 were extracted from 2 primary prostate cancer cohorts (TCGA, n = 492; MSK-primary, n = 856) and 3 metastatic prostate cancer cohorts (MSK-met, N = 432; MSK-mCSPC, N = 424; SU2CPNAS, n = 444) from cBioPortal. Expression data for the 336 genes was extracted from 6,135 radical prostatectomy samples from Decipher GRID registry. For survival analysis, patients were grouped into top 10% and top 25% by band expression and were compared with the remaining cohort. Hazard ratios were calculated using Cox proportional hazards models. RESULTS: Genes on chr8q were highly co-amplified and co-expressed. Copy number alterations and overexpression of chr8q genes in primary disease were associated with higher Gleason scores, increased risk of metastases, and increased prostate cancer specific mortality. Additionally, our data demonstrated high expression of MYC alone was not associated with differences in metastases free survival while high expression of other chr8q bands was associated with decreased metastases free survival. By combining chr8q data with an established genomic classifier like Decipher, we were able to develop a new model that was better at predicting metastases than Decipher alone. CONCLUSIONS: Our findings highlight the clinical utility of chr8q data, which can be used to improve prognostication and risk prediction in localized prostate cancer.

Factors associated with the use of salvage whole brain radiation therapy versus salvage stereotactic radiosurgery after initial stereotactic radiosurgery for brain metastases.

Objectives: Patients undergoing stereotactic radiosurgery (SRS) for brain metastases require additional radiation for relapse. Our objective is to determine the factors associated with salvage SRS versus whole brain radiation therapy (WBRT) for salvage of first intracranial failure (ICF) after upfront SRS. Method: We identified a cohort of 110 patients with brain metastases treated with SRS in the definitive or postoperative setting followed by subsequent salvage WBRT or SRS at least one month after initial SRS. Clinical and demographic characteristics were retrospectively recorded. Results: 78 Patients received SRS and 32 patients received WBRT at the time of first ICF. On multivariate analysis (MVA) factors associated with decreased use of salvage SRS were male gender (p=0.044) and local progression (p<0.001). Conclusions: Local progression and male gender were the strongest factors associated with selection of salvage WBRT. Possible etiologies of this difference could be provider or patient driven, but warrant further exploration.

Genomic alterations predictive of poor clinical outcomes in pan-cancer.

BACKGROUND: Genomic alterations are highly frequent across cancers, but their prognostic impact is not well characterized in pan-cancer cohorts. Here, we use pan-cancer cohorts from TCGA and MSK-IMPACT to evaluate the associations of common genomic alterations with poor clinical outcome. MATERIALS AND METHODS: Genomic alterations in commonly altered genes were extracted from Pan-Cancer TCGA and MSK-IMPACT cohorts. Multivariable Cox regression analyses stratified by cancer type defined adjusted hazard ratios (AHRs) for disease-specific survival (DSS), progression-free survival (PFS) and overall survival (OS). RESULTS: Using TCGA we identified 32 mutated genes, and 15 copy number (CN) genes with frequency >= 4% in 9,104 patients across 28 cancers. On UVA, having a TP53-mutations or any mutation in the 31 genes (mut31) were associated with worse PFS (HR: 1.22, p < 0.0001 and HR: 1.1, p = 0.04, respectively) and DSS (HR: 1.38, p < 0.0001, and HR: 1.16, p = 0.03, respectively). CDKN2A, PTEN deletions, and MYC-amplifications were associated with PFS and DSS (p < 0.05 for all). On MVA, including TP53-mutations, mut31, CDKN2A-deletion, PTEN-deletion, and MYC-amplification, all five alterations were independently prognostic of poor PFS and DSS. Similar results were observed in an independent cohort from MSK-IMPACT (n = 7,051) where TP53 was associated with poor OS independent of mut31 and CN alterations in CDKN2A, PTEN, and MYC in primary tumors (p < 0.0001). CONCLUSIONS: TP53-mutations, CDKN2A-deletion, PTEN-deletion, and MYC-amplification are independent pan-cancer prognostic genomic alterations.

A Review of Boron Neutron Capture Therapy: Its History and Current Challenges.

Mechanism of Action: External beam, whether with photons or particles, remains as the most common type of radiation therapy. The main drawback is that radiation deposits dose in healthy tissue before reaching its target. Boron neutron capture therapy (BNCT) is based on the nuclear capture and fission reactions that occur when 10B is irradiated with low-energy (0.0025 eV) thermal neutrons. The resulting 10B(n,α)7Li capture reaction produces high linear energy transfer (LET) α particles, helium nuclei (4He), and recoiling lithium-7 (7Li) atoms. The short range (5-9 µm) of the α particles limits the destructive effects within the boron-containing cells. In theory, BNCT can selectively destroy malignant cells while sparing adjacent normal tissue at the cellular levels by delivering a single fraction of radiation with high LET particles. History: BNCT has been around for many decades. Early studies were promising for patients with malignant brain tumors, recurrent tumors of the head and neck, and cutaneous melanomas; however, there were certain limitations to its widespread adoption and use. Current Limitations and Prospects: Recently, BNCT re-emerged owing to several developments: (1) small footprint accelerator-based neutron sources; (2) high specificity third-generation boron carriers based on monoclonal antibodies, nanoparticles, among others; and (3) treatment planning software and patient positioning devices that optimize treatment delivery and consistency.

Prophylactic Radiotherapy for Prevention of Heterotopic Ossification After Periacetabular Fractures: A Review of Efficacy and Associated Conditions.

Prophylactic radiotherapy (XRT) is a commonly used treatment to decrease heterotopic ossification (HO) in patients with traumatic hip injuries. We conducted a retrospective review of patients at risk for HO who underwent XRT. Of the patients reviewed, 27.3% developed radiographic HO, 11.2% developed symptoms, and 2.0% required resection surgery. Patients were divided into primary (n = 71) and secondary prophylaxis (n = 27) cohorts. In the primary group, 25.0% developed radiographic HO, 5.6% developed symptoms, and 0 required surgery. In the secondary cohort, 33.3% of patients developed new radiographic HO, and 25.9% were symptomatic: four had a Brooker score of 3, and three had a score of 4 (p = 0.03), and 7.4% required surgical resection. (Journal of Surgical Orthopaedic Advances 31(2):113-118, 2022).

Musculoskeletal Metastasis From Soft-tissue Sarcomas: A Review of the Literature.

Soft-tissue sarcomas are a rare and extremely heterogeneous group of cancers, representing <1% of all human malignancies. The lungs are the most common site of distant metastasis, followed by the bone, lymph nodes, liver, brain, and subcutaneous tissue. Clinical experience suggests that skeletal metastasis is part of the natural history affecting the prognosis and quality of life in these patients. Approximately 2.2% of patients have skeletal metastasis at diagnosis. However, up to 10% will develop skeletal metastasis after a mean interval of 21.3 months. Although systemic therapy with conventional chemotherapy remains the primary treatment modality for those with metastatic sarcoma, increased survival has been achieved in selected patients who receive multimodality therapy, including surgery, for their metastatic disease. The 5-year overall survival of patients with isolated bone metastases was 41.2% (26.9% to 54.9%), which decreased to 32.9% (21.2% to 45.1%) in the setting of combined bone and lung metastases. Moreover, the resection of the primary soft-tissue sarcoma is a predictor of survival, resulting in a 58% decrease in mortality after surgery (hazard ratio, 0.42, P = 0.013). Understanding the effect of these metastases on patient survival may influence imaging, surveillance, and treatment decisions.

Bone Marrow Suppression during Postoperative Radiation for Bladder Cancer and Comparative Benefit of Proton Therapy-Phase 2 Trial Secondary Analysis.

PURPOSE: For patients with high-risk bladder cancer (pT3+ or N+), local regional failure remains a challenge after chemotherapy and cystectomy. An ongoing prospective phase 2 trial (NCT01954173) is examining the role of postoperative photon radiation therapy for high-risk patients using volumetric modulated arc therapy. Proton beam therapy (PBT) may be beneficial in this setting to reduce hematologic toxicity. We evaluated for dosimetric relationships with pelvic bone marrow (PBM) and changes in hematologic counts before and after pelvic radiation therapy and explored the potential of PBT treatment plans to achieve reductions in PBM dose. MATERIALS AND METHODS: All enrolled patients were retrospectively analyzed after pelvic radiation per protocol with 50.4 to 55.8 Gy in 28 to 31 fractions. Comparative PBT plans were generated using pencil-beam scanning and a 3-beam multifield optimization technique. Changes in hematologic nadirs were assessed using paired t test. Correlation of mean nadirs and relative PBM dose levels were assessed using the Pearson correlation coefficient (CC). RESULTS: Eighteen patients with a median age of 70 were analyzed. Mean cell count values after radiation therapy decreased compared with preradiation therapy values for white blood cells (WBCs), absolute neutrophil count (ANC), absolute lymphocyte count (all P < .001), and platelets (P = .03). Increased mean PBM dose was associated with lower nadirs in WBC (Pearson CC -0.593, P = .02), ANC (Pearson CC -0.597, P = .02), and hemoglobin (Pearson CC -0.506, P = .046), whereas the PBM V30 to V40 correlated with lower WBC (Pearson CC -0.512 to -0.618, P < .05), and V20 to V30 correlated with lower ANC (Pearson CC -0.569 to -0.598, P < .04). Comparative proton therapy plans decreased the mean PBM dose from 26.5 Gy to 16.1 Gy (P < .001) and had significant reductions in the volume of PBM receiving doses from 5 to 40 Gy (P < .001). CONCLUSION: Increased PBM mean dose and V20 to V40 were associated with lower hematologic nadirs. PBT plans reduced PBM dose and may be a valuable strategy to reduce the risk of hematologic toxicity in these patients.

Clinicogenomic characterization of prostate cancer liver metastases.

BACKGROUND: The site of prostate cancer metastasis is an important predictor of oncologic outcomes, however, the clinicogenomic characteristics associated with the site are not well-defined. Herein, we characterize the genomic alterations associated with the metastatic site of prostate cancer. METHODS: We analyzed clinical and genomic data from prostate cancer patients with metastatic disease and known metastatic sites from publicly available targeted sequencing data. RESULTS: Prostate cancer metastasis to the liver versus other sites of metastasis conferred a high hazard for death in patients with metastatic prostate cancer (HR: 3.96, 95% CI: 2.4-6.5, p < 0.0001). Genomic analysis of metastatic tissues of prostate cancer-specific genes demonstrated that liver metastases were more enriched with MYC amplification (29.5% vs. 9.8%, FDR = 0.001), PTEN deletion (42% vs. 20.8%, FDR = 0.005), and PIK3CB amplification (8.2% vs. 0.9, FDR = 0.005) compared to other sites. No point mutations were significantly associated with liver metastasis compared to other metastatic sites. CONCLUSION: Liver metastases in prostate cancer are associated with poor survival and aggressive genomic features, including MYC-amplification, PTEN-deletion, and PIK3CB-amplification. These findings could have prognostic, treatment, and trial implications.

Primary Versus Secondary Radiotherapy for Heterotopic Ossification Prevention About the Elbow.

OBJECTIVES: To examine the efficacy and safety of radiotherapy for the prevention of heterotopic ossification (HO) about the elbow. DESIGN: Retrospective chart review. SETTING: Level 1 trauma center. PATIENTS/PARTICIPANTS: Two hundred and twenty-nine patients who received prophylactic radiotherapy (XRT) over a 15-year period were identified. Patients were included if they received XRT to the elbow joint and had at least 12 weeks of follow-up after XRT. Fifty-four patients were ultimately included. INTERVENTION: All patients were treated with a single dose of 7 Gy. Ninety-eight percentage of patients received XRT within 24 hours after surgery, and all patients received XRT within 72 hours after surgery. MAIN OUTCOMES MEASUREMENTS: The primary study measures evaluated were the presence or absence of clinically symptomatic HO and the presence of radiographic HO after XRT to the elbow joint. RESULTS: Eighteen patients were treated with XRT after a traumatic injury requiring surgery (primary prophylaxis), and 36 were treated with XRT after excision surgery to remove HO which had already formed (secondary prophylaxis). In the primary cohort, 16.7% developed symptomatic HO after XRT and 11.1% required surgery to resect the heterotopic bone. In the secondary cohort, 11.1% developed symptomatic HO after surgery and XRT and 5.5% required resection surgery. No secondary malignancies were identified. CONCLUSIONS: Our findings suggest that XRT for elbow HO may be safe and effective for both primary and secondary HO. XRT for HO was not shown to be associated with radiation-induced sarcoma in this series, at least in the short term. Further study in a large patient population with extended follow-up is required to better characterize populations at high risk for development of HO and secondary malignancy. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.