The Right Dose: Results of a Patient Advocate-Led Survey of Individuals With Metastatic Breast Cancer Regarding Treatment-Related Side Effects and Views About Dosage Assessment to Optimize Quality of Life.

PURPOSE: Although patients with metastatic breast cancer (MBC) have been living longer with the advent of more effective treatments such as targeted therapy and immunotherapy, the disease remains incurable, and most patients will undergo therapy indefinitely. When beginning therapy, patients are typically prescribed dose often based upon the maximum tolerated dose identified in phase I clinical trials. However, patients' perspectives about tolerability and willingness to discuss individualized dosing of drugs upon initiation of a new regimen and throughout the course of treatment have not been comprehensively evaluated. METHODS: Patient advocates and medical oncologists from the Patient-Centered Dosing Initiative (PCDI) developed a survey to ascertain the prevalence and severity of MBC patients' treatment-related side effects, the level of patient-physician communication, mitigation strategies, perception about the relative efficacy of higher versus lower doses, and willingness to discuss alternative dosing. The PCDI distributed the anonymous confidential online survey in August 2020 to individuals with self-reported MBC. RESULTS: One thousand and two hundred twenty-one patients with MBC completed the survey. 86.1% (n = 1,051) reported experiencing at least one significant treatment-related side effect, and of these, 20.3% (n = 213) visited the emergency room/hospital and 43.2% (n = 454) missed at least one treatment. Nearly all patients with side effects (97.6%, n = 1,026) informed their doctor and 81.7% (n = 838) received assistance. Of the 556 patients given a dose reduction for side-effect mitigation, 82.6% (n = 459) reported relief. Notably, majority of patients (53.3%, n = 651) do not believe that higher dose is always more effective than lower dose, and 92.3% (n = 1,127) would be willing to discuss flexible dosing options with their physicians based upon personal characteristics to optimize quality of life. CONCLUSION: Given that the majority of patients with MBC experienced at least one substantial treatment-related side effect and most patients given a dose reduction reported improvement, innovative dosage-related strategies are warranted to sustain and improve patients' well-being. Patient-physician discussions in which the patient's unique attributes and circumstances are assessed upon initiation of new treatment and throughout the course of therapy may facilitate the identification of the most favorable dose for each patient, and the majority of patients would be receptive to this approach.

Racial and ethnic disparities in a real-world precision oncology data registry.

Biorepositories enable precision oncology research by sharing clinically annotated genomic data, but it remains unknown whether these data registries reflect the true distribution of cancers in racial and ethnic minorities. Our analysis of Project Genomics Evidence Neoplasia Information Exchange (GENIE), a real-world cancer data registry designed to accelerate precision oncology discovery, indicates that minorities do not have sufficient representation, which may impact the validity of studies directly comparing mutational profiles between racial/ethnic groups and limit generalizability of biomarker discoveries to all populations.

Diversity Trends by Sex and Underrepresented in Medicine Status Among US Radiation and Medical Oncology Faculty Over 5 Decades.

IMPORTANCE: It remains unclear how the historical exclusion of women and racial and ethnic minority groups from medical training, and therefore the oncologic subspecialties, has contributed to rates of faculty diversity among oncology departments over time. Oncologic faculty diversity is an important initiative to help improve care and address health disparities for an increasingly diverse US population with cancer. OBJECTIVES: To report trends in academic faculty representation by sex and by race and ethnicity for radiation oncology (RO) and medical oncology (MO) departments and to describe comparisons with the general US population, medical students, RO and MO trainees, clinical department chairs, and faculty in other departments. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional analysis used data from the Association of American Medical Colleges to analyze trends by sex and by race and ethnicity among full-time US faculty in RO and MO departments from 1970 through 2019. Data were analyzed between October 2020 and April 2021. MAIN OUTCOMES AND MEASURES: Proportions of women and individuals from underrepresented in medicine (URM) racial and ethnic groups (Black, Hispanic, and Indigenous individuals) were calculated among RO and MO academic departments; trends were analyzed over 5 decades. These proportions were compared with cohorts already described. In addition, proportions of women and URM individuals were calculated by faculty rank among RO and MO departments. RESULTS: In 1970, there were 119 total faculty in RO (10 women [8.4%] and 2 URM [1.7%]) and 87 total faculty in MO (11 women [12.6%] and 7 URM [8.0%]). In 2019, there were 2115 total faculty in RO (615 women [29.1%] and 108 URM [5.1%]) and 819 total faculty in MO (312 women [38.1%] and 47 URM [5.7%]). Total faculty numbers increased over time in both RO and MO. Faculty representation of URM women proportionally increased by 0.1% per decade in both RO (95% CI, 0.005%-0.110%; P <. 001 for trend) and MO (95% CI, -0.03% to 0.16%; P = .06 for trend) compared with non-URM women faculty, which increased by 0.4% (95% CI, 0.25%-0.80%) per decade in RO and 0.7% (95% CI, 0.47%-0.87%) per decade in MO (P < .001 for trend for both). Faculty representation of URM men did not significantly change for RO (0.03% per decade [95% CI, -0.008% to 0.065%]; P = .09 for trend) or MO (0.003% per decade [95% CI, -0.13% to 0.14%]; P = .94 for trend). Representation of both women and URM individuals among both specialties was lower than their representation in the US population in both 2009 and 2019. Across all cohorts studied, RO faculty had the lowest URM representation in 2019 at 5.1%. At every rank in 2019, the number of total URM faculty represented among both MO and RO remained low (MO: instructor, 2 of 44 [5%]; assistant professor, 18 of 274 [7%]; associate professor, 13 of 177 [7%]; full professor, 13 of 276 [5%]; and RO: instructor, 9 of 147 [6%]; assistant professor, 57 of 927 [6%]; associate professor, 20 of 510 [4%]; full professor, 18 of 452 [4%]). CONCLUSIONS AND RELEVANCE: This cross-sectional study suggests that RO and MO academic faculty have increased the representation of women over time, while URM representation has lagged. The URM trends over time need further investigation to inform strategies to improve URM representation in RO and MO.

Clinical needs assessment for sexual health among cancer patients receiving pelvic radiation: Implications for development of a radiation oncology sexual health clinic.

BACKGROUND: Cancer patients treated with pelvic radiation therapy (RT) often experience sexual health-related side effects during and following treatment. A clinical needs assessment was used to evaluate sexual health needs and to determine how needs differed between patients receiving and who had completed RT. METHODS AND MATERIALS: A questionnaire was used to evaluate sexual health needs among patients treated with pelvic RT. All answers were rated using a 4-point Likert scale. Convenience sampling was used, and patients were stratified by whether they were on-treatment or in follow-up. Charts were reviewed for demographic, diagnostic, and treatment information. Pearson's χ2 test and logistic regression analysis were used to analyze the associations between sexual health-related topics and clinical variables. RESULTS: A total of 107 of 109 (98%) invited patients completed the questionnaire (46 females, 61 males; 52 undergoing RT, 54 completed RT). Most (75%) reported some degree of change in sexual health from the effects of cancer and/or treatment; 22% and 28% reported "quite a bit" or "very much" change, respectively. Sixty-nine percent reported that they experienced some degree of distress from sexual health changes (28% reported "very much" or "quite a bit" of distress). Seventy-six percent "agreed" or "strongly agreed" that they were interested in access to a multidisciplinary sexual health clinic (MSHC). Compared with patients currently receiving RT, patients in follow-up were significantly more likely to report worsening degrees of "change" (P = .008) and "distress" (P = .04) and to express interest in having access to an MSHC (P = .03). CONCLUSION: The majority of patients receiving pelvic RT reported a change in sexual health with associated distress, with more reports among those in follow-up. Patients undergoing pelvic RT expressed a high interest in attending a radiation oncology MSHC. Our findings emphasize the important role radiation oncologists can play in the quality of life of our patients.

Incidence, Clinicopathological Risk Factors, Management and Outcomes of Nonmuscle Invasive Recurrence after Complete Response to Trimodality Therapy for Muscle Invasive Bladder Cancer.

PURPOSE: We describe the incidence, clinicopathological risk factors, management and outcomes of recurrent nonmuscle invasive bladder cancer after a complete response to trimodality therapy of muscle invasive bladder cancer. MATERIALS AND METHODS: We retrospectively reviewed the records of 342 patients with cT2-4aN0M0 muscle invasive bladder cancer and a complete response after trimodality therapy from 1986 to 2013. Using competing risks analyses we examined the association between baseline clinicopathological variables and nonmuscle invasive bladder cancer outcomes. Kaplan-Meier and the generalized Fleming-Harrington test were used to compare disease specific and overall survival. RESULTS: At a median followup of 9 years nonmuscle invasive bladder cancer recurred in 85 patients (25%) who had had a complete response. On Kaplan-Meier analysis baseline carcinoma in situ was associated with recurrent nonmuscle invasive bladder cancer (p = 0.02). However, on multivariate analysis carcinoma in situ and other baseline clinicopathological characteristics did not predict such recurrence. Patients with recurrent nonmuscle invasive bladder cancer had worse 10-year disease specific survival than those without recurrence (72.1% vs 78.4%, p = 0.002), although overall survival was similar (p = 0.66). Of the 39 patients (46%) who received adjuvant intravesical bacillus Calmette-Guérin 29 (74%) completed induction therapy and 19 (49%) reported bacillus Calmette-Guérin toxicity. Three-year recurrence-free and progression-free survival after induction bacillus Calmette-Guérin was 59% and 63%, respectively. CONCLUSIONS: After a complete response to trimodality therapy nonmuscle invasive bladder cancer recurred in 25% of patients, developing in some of them more than a decade after trimodality therapy. No baseline clinicopathological characteristics were associated with such recurrence after a complete response. Patients with nonmuscle invasive bladder cancer recurrence had worse disease specific survival than those without such recurrence but similar overall survival. Adjuvant intravesical bacillus Calmette-Guérin had a reasonable toxicity profile and efficacy in this population. Properly selected patients with recurrent nonmuscle invasive bladder cancer after a complete response may avoid immediate salvage cystectomy.

Outcomes of proton therapy for the treatment of uveal metastases.

PURPOSE/OBJECTIVE(S): Radiation therapy can be used to treat uveal metastases with the goal of local control and improvement of quality of life. Proton therapy can be used to treat uveal tumors efficiently and with expectant minimization of normal tissue injury. Here, we report the use of proton beam therapy for the management of uveal metastases. METHODS AND MATERIALS: A retrospective chart review was made of all patients with uveal metastases treated at our institution with proton therapy between June 2002 and June 2012. Patient and tumor characteristics, fractionation and dose schemes, local control, and toxicities are reported. RESULTS: Ninety patients were identified. Of those, 13 were excluded because of missing information. We report on 77 patients with 99 affected eyes with available data. Patients were 68% female, and the most common primary tumor was breast carcinoma (49%). The median age at diagnosis of uveal metastasis was 57.9 years. Serous retinal detachment was seen in 38% of treated eyes. The median follow-up time was 7.7 months. The median dose delivered to either eye was 20 Gy(relative biological effectiveness [RBE]) in 2 fractions. Local control was 94%. The median survival after diagnosis of uveal metastases was 12.3 months (95% confidence interval, 7.7-16.8). Death in all cases was secondary to systemic disease. Radiation vasculopathy, measured decreased visual acuity, or both was observed in 50% of evaluable treated eyes. The actuarial rate of radiation vasculopathy, measured decreased visual acuity, or both was 46% at 6 months and 73% at 1 year. The 6 eyes with documented local failure were successfully salvaged with retreatment. CONCLUSIONS: Proton therapy is an effective and efficient means of treating uveal metastases. Acutely, the majority of patients experience minor adverse effects. For longer-term survivors, the risk of retinal injury with vision loss increases significantly over the first year.

Patterns of failure after proton therapy in medulloblastoma; linear energy transfer distributions and relative biological effectiveness associations for relapses.

PURPOSE: The pattern of failure in medulloblastoma patients treated with proton radiation therapy is unknown. For this increasingly used modality, it is important to ensure that outcomes are comparable to those in modern photon series. It has been suggested this pattern may differ from photons because of variations in linear energy transfer (LET) and relative biological effectiveness (RBE). In addition, the use of matching fields for delivery of craniospinal irradiation (CSI) may influence patterns of relapse. Here we report the patterns of failure after the use of protons, compare it to that in the available photon literature, and determine the LET and RBE values in areas of recurrence. METHODS AND MATERIALS: Retrospective review of patients with medulloblastoma treated with proton radiation therapy at Massachusetts General Hospital (MGH) between 2002 and 2011. We documented the locations of first relapse. Discrete failures were contoured on the original planning computed tomography scan. Monte Carlo calculation methods were used to estimate the proton LET distribution. Models were used to estimate RBE values based on the LET distributions. RESULTS: A total of 109 patients were followed for a median of 38.8 months (range, 1.4-119.2 months). Of the patients, 16 experienced relapse. Relapse involved the supratentorial compartment (n=8), spinal compartment (n=11), and posterior fossa (n=5). Eleven failures were isolated to a single compartment; 6 failures in the spine, 4 failures in the supratentorium, and 1 failure in the posterior fossa. The remaining patients had multiple sites of disease. One isolated spinal failure occurred at the spinal junction of 2 fields. None of the 70 patients treated with an involved-field-only boost failed in the posterior fossa outside of the tumor bed. We found no correlation between Monte Carlo-calculated LET distribution and regions of recurrence. CONCLUSIONS: The most common site of failure in patients treated with protons for medulloblastoma was outside of the posterior fossa. The most common site for isolated local failure was the spine. We recommend consideration of spinal imaging in follow-up and careful attention to dose distribution in the spinal junction regions. Development of techniques that do not require field matching may be of benefit. We did not identify a direct correlation between lower LET values and recurrence in medulloblastoma patients treated with proton therapy. Patterns of failure do not appear to differ from those in patients treated with photon therapy.

Linear energy transfer-guided optimization in intensity modulated proton therapy: feasibility study and clinical potential.

PURPOSE: To investigate the feasibility and potential clinical benefit of linear energy transfer (LET) guided plan optimization in intensity modulated proton therapy (IMPT). METHODS AND MATERIALS: A multicriteria optimization (MCO) module was used to generate a series of Pareto-optimal IMPT base plans (BPs), corresponding to defined objectives, for 5 patients with head-and-neck cancer and 2 with pancreatic cancer. A Monte Carlo platform was used to calculate dose and LET distributions for each BP. A custom-designed MCO navigation module allowed the user to interpolate between BPs to produce deliverable Pareto-optimal solutions. Differences among the BPs were evaluated for each patient, based on dose-volume and LET-volume histograms and 3-dimensional distributions. An LET-based relative biological effectiveness (RBE) model was used to evaluate the potential clinical benefit when navigating the space of Pareto-optimal BPs. RESULTS: The mean LET values for the target varied up to 30% among the BPs for the head-and-neck patients and up to 14% for the pancreatic cancer patients. Variations were more prominent in organs at risk (OARs), where mean LET values differed by a factor of up to 2 among the BPs for the same patient. An inverse relation between dose and LET distributions for the OARs was typically observed. Accounting for LET-dependent variable RBE values, a potential improvement on RBE-weighted dose of up to 40%, averaged over several structures under study, was noticed during MCO navigation. CONCLUSIONS: We present a novel strategy for optimizing proton therapy to maximize dose-averaged LET in tumor targets while simultaneously minimizing dose-averaged LET in normal tissue structures. MCO BPs show substantial LET variations, leading to potentially significant differences in RBE-weighted doses. Pareto-surface navigation, using both dose and LET distributions for guidance, provides the means for evaluating a large variety of deliverable plans and aids in identifying the clinically optimal solution.

The use and QA of biologically related models for treatment planning: short report of the TG-166 of the therapy physics committee of the AAPM.

Treatment planning tools that use biologically related models for plan optimization and/or evaluation are being introduced for clinical use. A variety of dose-response models and quantities along with a series of organ-specific model parameters are included in these tools. However, due to various limitations, such as the limitations of models and available model parameters, the incomplete understanding of dose responses, and the inadequate clinical data, the use of biologically based treatment planning system (BBTPS) represents a paradigm shift and can be potentially dangerous. There will be a steep learning curve for most planners. The purpose of this task group is to address some of these relevant issues before the use of BBTPS becomes widely spread. In this report, the authors (1) discuss strategies, limitations, conditions, and cautions for using biologically based models and parameters in clinical treatment planning; (2) demonstrate the practical use of the three most commonly used commercially available BBTPS and potential dosimetric differences between biologically model based and dose-volume based treatment plan optimization and evaluation; (3) identify the desirable features and future directions in developing BBTPS; and (4) provide general guidelines and methodology for the acceptance testing, commissioning, and routine quality assurance (QA) of BBTPS.

Proton beams to replace photon beams in radical dose treatments.

With proton beam radiation therapy a smaller volume of normal tissues is irradiated at high dose levels for most anatomic sites than is feasible with any photon technique. This is due to the Laws of Physics, which determine the absorption of energy from photons and protons. In other words, the dose from a photon beam decreases exponentially with depth in the irradiated material. In contrast, protons have a finite range and that range is energy dependent. Accordingly, by appropriate distribution of proton energies, the dose can be uniform across the target and essentially zero deep to the target and the atomic composition of the irradiated material. The dose proximal to the target is lower compared with that in photon techniques, for all except superficial targets This resultant closer approximation of the planning treatment volume (PTV) to the CTV/GTV (grossly evident tumor volume/subclinical tumor extensions) constitutes a clinical gain by definition; i.e. a smaller treatment volume that covers the target three dimensionally for the entirety of each treatment session provides a clinical advantage. Several illustrative clinical dose distributions are presented and the clinical outcome results are reviewed briefly. An important technical advance will be the use of intensity modulated proton radiation therapy, which achieves contouring of the proximal edge of the SOBP (spread out Bragg peak) as well as the distal edge. This technique uses pencil beam scanning. To permit further progressive reductions of the PTV, 4-D treatment planning and delivery is required. The fourth dimension is time, as the position and contours of the tumor and the adjacent critical normal tissues are not constant. A potentially valuable new method for assessing the clinical merits of each of a large number of treatment plans is the evaluation of multidimensional plots of the complication probabilities for each of 'n' critical normal tissues/ structures for a specified tumor control probability. The cost of proton therapy compared with that of very high technology photon therapy is estimated and evaluated. The differential is estimated to be approximately 1.5 provided there were to be no charge for the original facility and that there were sufficient patients for operating on an extended schedule (6-7 days of 14-16 h) with > or = two gantries and one fixed horizontal beam.