Prognostic Effect of Mismatch Repair Status in Early-Stage Endometrial Cancer Treated With Adjuvant Radiation: A Multi-institutional Analysis.

PURPOSE: The aim of this work was to report the effect of mismatch repair (MMR) status on outcomes of patients with stage I-II endometrioid endometrial adenocarcinoma (EEC) who receive adjuvant radiation therapy. METHODS AND MATERIALS: This is a multi-institutional retrospective cohort study across 11 institutions in North America. Patients with known MMR status and stage I-II EEC status postsurgical staging were included. Overall survival (OS) and recurrence-free survival (RFS) rates were estimated via the Kaplan-Meier method. Univariable and multivariable analyses were performed via Cox proportional hazard models for RFS and OS. Statistical analyses were conducted using SPSS version 27. RESULTS: In total, 744 patients with a median age at diagnosis of 65 years (IQR, 58-71) were included. Most patients were White (69.4%) and had Federation of Obstetrics and Gynecology 2009 stage I (84%) and Federation of Obstetrics and Gynecology grade 1 to 2 (73%). MMR deficiency was reported in 234 patients (31.5%), whereas 510 patients (68.5%) had preserved MMR. External beam radiation therapy with or without vaginal brachytherapy was delivered to 186 patients (25%), whereas 558 patients (75%) received vaginal brachytherapy alone. At a median follow-up of 43.5 months, the estimated crude OS and RFS rates for the entire cohort were 92.5% and 84%, respectively. MMR status was significantly correlated with RFS. RFS was inferior for MMR deficiency compared with preserved MMR (74.3% vs 88.6%, P < .001). However, no difference in OS was seen (90.8% vs 93.2%, P = .5). On multivariable analysis, MMR deficiency status was associated with worse RFS (hazard ratio, 1.86; P = .001) but not OS. CONCLUSIONS: MMR status was independently associated with RFS but not OS in patients with early-stage EEC who were treated with adjuvant radiation therapy. These findings suggest that differential approaches to surveillance and/or treatment based on MMR status could be warranted.

Cancer Center Staff Satisfaction: Descriptive Results of a Canadian Study.

Caring for cancer patients is generally considered very rewarding work, but it can also be stressful and demanding. Therefore, it is important for oncology healthcare professionals to feel satisfied with their work environment in order to provide the best care possible. An ethics-approved 61-item staff satisfaction survey was developed in-house to gain insights regarding workplace satisfaction among all staff at The Ottawa Hospital Cancer Center. Descriptive statistics were used to analyze the responses. A total of 478 individuals completed the online survey, with 75.1% women, 23.2% men, and 1.7% preferring not to say. This represented the vast majority (>75%) of cancer center staff. The approximate breakdown according to healthcare professional type was as follows: 21% nurses, 20% radiation therapists, 18% physicians, 13% clerical staff, and 28% other types of staff. Almost all (97.4%) generally enjoyed their work, with 60% stating "very much" and 37.4% stating "a little bit", and 93.3% found working with cancer patients rewarding. The overall satisfaction level at work was high, with 30.1% reporting "very satisfied" and 54.2% "somewhat satisfied". However, in terms of their work being stressful, 18.6% stated it was "very much" and 62.1% "a little bit". Also, in terms of their workload, 61.3% stated it was "very busy" and 10% stated it was "excessively busy". The most enjoyable aspects of work were listed as interactions with colleagues, interactions with patients, and learning new things. The least enjoyable aspects of work were excessive workload, a perceived unsupportive work environment, and technology problems. Levels of satisfaction and stress at work varied according to role at the cancer center. Most cancer center staff seem to enjoy their work and find it rewarding. However, the work environment can be challenging and stressful. Areas for improvement include managing workloads, ensuring staff feel supported, and improving the user-friendliness of technology.

Cranial Radiation Therapy as Salvage in the Treatment of Relapsed Primary CNS Lymphoma.

Primary central nervous system lymphoma (PCNSL) is a rare malignancy. Standard of care is upfront high-dose methotrexate (HD-MTX) chemotherapy, while cranial radiation is more commonly used in the salvage setting. In this retrospective study, we aimed to investigate the safety and efficacy of salvage cranial radiation in PCNSL. PCNSL patients who received upfront HD-MTX chemotherapy and salvage cranial radiation after treatment failure between 1995 and 2018 were selected. Radiological response to cranial radiation was assessed as per Response Assessment in Neuro-Oncology Criteria. Twenty one patients were selected (median age 59.9 years), with median follow-up of 19.9 months. Fourteen patients (66.7%) received a boost to the gross tumour volume (GTV). Four patients (19.0%) sustained grade ≥2 treatment-related neurotoxicity post-completion of cranial radiation. Of the 19 patients who had requisite MRI with gadolinium imaging available for Response Assessment in Neuro-Oncology (RANO) criteria assessment, 47.4% achieved complete response, 47.4% achieved partial response, and 5.3% of patients exhibited stable disease. Higher dose to the whole brain (>30 Gy) was associated with higher rate of complete response (63.6%) than lower dose (≤30 Gy, 37.5%), while boost dose to the gross disease was also associated with higher rate of complete response (61.5%) compared with no boost dose (33.3%). Median overall survival was 20.0 months. PCNSL patients who relapsed following upfront chemotherapy showed a high rate of response to salvage cranial radiation, especially in those receiving greater than 30 Gy to the whole brain and boost to gross disease.

Cost-Utility Analysis of Radiation Treatment Modalities for Intermediate-Risk Prostate Cancer.

INTRODUCTION: Variable costs of different radiation treatment modalities have played an important factor in selecting the most appropriate treatment for patients with intermediate-risk prostate cancer. METHODS: Analysis using a Markov model was conducted to simulate 20-year disease trajectory, quality-adjusted life years (QALYs) and health system costs of a cohort of intermediate-risk prostate cancer patients with mean age of 60 years. Clinical outcomes on toxicity and disease recurrence were measured and a probabilistic sensitivity analysis was performed, varying input parameters simultaneously according to their distributions. RESULTS: Among the six radiation treatment modalities, including conventionally fractionated intensity-modulated radiation therapy (IMRT), hypofractionated IMRT, IMRT combined with high-dose-rate (HDR) brachytherapy, HDR brachytherapy monotherapy, low-dose-rate brachytherapy monotherapy, and stereotactic body radiotherapy (SBRT), SBRT was found to be more cost-effective when compared with LDR-b and other treatment modalities, resulting in an incremental cost-utility ratio of $2985 per QALY. CONCLUSIONS: Stereotactic body radiotherapy is the most cost-effective radiation treatment modality in treatment of intermediate-risk prostate cancer, while treatment toxicity and cost data are the key drivers of the cost-utility. Further work is required with long-term follow-up for SBRT.

Radiation-induced brain injury in patients with meningioma treated with proton or photon therapy.

INTRODUCTION: Radiation therapy is often used to treat meningioma with adverse features or when unresectable. Proton therapy has advantages over photon therapy in reducing integral dose to the brain. This study compared the incidence of radiological and clinical adverse events after photon versus proton therapy in the treatment of meningioma. METHODS: A retrospective review was conducted on patients with meningioma treated with proton or photon therapy at two high-volume tertiary cancer centers. Patients with a history of prior radiation therapy (RT) or less than 3 months of follow-up were excluded. Post-RT imaging changes were categorized into abnormal T2 signal intensities (T2 changes) or abnormal T1 post-contrast and T2 signal intensities (T1c+T2 changes) on magnetic resonance imaging (MRI). Clinical outcomes of adverse events and survival were compared between the proton and photon therapies. RESULTS: Among the total of 77 patients, 38 patients received proton therapy and 39 patients received photon therapy. The median age at diagnosis was 55 years and median follow-up was 2.2 years. No significant differences in symptomatic adverse events were observed between the two groups: grade ≥ 2 adverse events were seen in 4 (10.5%) patients in the proton group and 3 (7.7%) patients in the photon group (p = 0.67). The 2-year cumulative incidences of T2 changes were 38.3% after proton therapy and 47.7% after photon therapy (p = 0.53) and the 2-year cumulative incidences of T1c+T2 changes were 26.8% after proton therapy and 5.3% after photon therapy (p = 0.02). One patient experienced grade ≥ 4 adverse event in each group (p = 0.99). Estimated 2-year progression-free survival was 79.5% (proton therapy 76.0% vs. photon therapy 81.3%, p = 0.66) and 2-year overall survival was 89.7% (proton therapy 86.6% vs. photon therapy 89.3%, p = 0.65). CONCLUSIONS: Following RT, high rates of T2 changes were seen in meningioma patients regardless of treatment modality. Proton therapy was associated with significantly higher rates of T1c+T2 changes compared with photon therapy, but severe adverse events were uncommon in both groups and survival outcomes were comparable between the two groups. Future studies will aim at correlating the MRI changes with models that can be incorporated into RT planning to avoid toxicity.

Can we rely on surgical clips placed during oncoplastic breast surgery to accurately delineate the tumor bed for targeted breast radiotherapy?

PURPOSE: Oncoplastic breast surgery (OBS) is gaining popularity among surgeons for breast-conserving surgery treatments. OBS relies on complex relocation and deformation of breast tissue involving the tumor bed (TB). In this study, we investigate the validity of using surgical clips with OBS for accurate TB delineation in adjuvant, targeted breast radiotherapy. METHODS: Different OBS techniques were simulated on realistic breast phantoms. Surgical clips were used to demarcate the TB. Following tumor resection and closure, the true TB (TBTrue) was extracted. Each phantom was CT imaged at several phases of surgery in order to record pre- and post-OBS closure surgical clip displacements. Two senior radiation oncologists (ROs) were asked to delineate TBs on CTs by relying on surgical clips placed as per standard protocol, and by referring to operative notes. Their original contours, as well as those expanded using 5-15 mm margins, were compared with the accurate TBTrue using the dice similarity coefficient (DSC), Hausdorff Distance (HD), and over- and under-contoured volumes. Inter- and intra-RO contour agreements were also evaluated. RESULTS: Post-OBS surgical clips were significantly displaced outside the original breast quadrant. Inter- and Intra-RO TB contours were consistent, yet systematically differed from TBTrue (DSC values range = 0.38 to 0.69, and maximum HD range = 17.8 mm to 38.0 mm). Using expansion margins did not improve contour congruence and caused significant over-contoured volumes. CONCLUSION: Following OBS, surgical clips alone are not reliable radiographic surrogates of TB locations and accurate TB delineation is challenging. For complex OBS cases, indication of any type of partial breast irradiation is very questionable.

Dose-sparing effect of deep inspiration breath hold technique on coronary artery and left ventricle segments in treatment of breast cancer.

BACKGROUND AND PURPOSE: The risk of radiation-induced cardiac injury remains a challenging problem in the treatment of breast cancer. Certain cardiac structures receive higher doses than others, which results in variable frequencies of radiation-induced injuries across these structures. Radiation dose can be reduced using the deep inspiration breath hold (DIBH) technique. We aimed to investigate the dose reductions from DIBH in individual cardiac segments. MATERIALS AND METHODS: A dosimetric analysis was performed on left-sided breast cancer patients who underwent breast-conserving surgery and whole breast irradiation. Radiation doses to the cardiac structures were compared between the DIBH and free-breathing (FB) techniques and the dose reductions with DIBH were correlated to the lung expansion. RESULTS: For the 75 patients included in our study, DIBH effectively reduced doses to the heart, left lung, left anterior descending coronary artery (LAD) and left ventricle (LV), but the degree of dose reductions was variable across different structures. The absolute dose reductions were greatest in the distal LAD (14.4 Gy) and apical LV (12.1 Gy) segments, compared with the other LAD (middle 9.7 Gy, proximal 1.6 Gy) and LV (anterior 5.3 Gy, lateral 2.9 Gy, septal 2.0 Gy, inferior 0.2 Gy) segments. Left lung expansion was significantly correlated with the dose reductions in the LAD (Spearman's rank correlation coefficient, ρ, 0.304) and LV (ρ, 0.420) segments. CONCLUSIONS: Our study demonstrates the dose-sparing effects of DIBH in various cardiac structures, especially the distal LAD and apical LV segments. The large dose reductions seen in the distal LAD and apical LV segments could potentially translate into clinical benefit of reduced cardiac toxicity, as these structures have been previously shown to receive the highest doses and are associated with radiation-induced injury.

Treatment of Early Stage High-Risk Endometrioid-Type Endometrial Cancer and Patterns of Disease Relapse: A Retrospective Analysis.

PURPOSE: A recently published randomized controlled trial has demonstrated that in patients with endometrial cancer with high-risk features, the addition of chemotherapy to radiation therapy, compared with radiation therapy alone, resulted in a significant improvement in failure-free survival. However, in the study, the effect of chemotherapy was limited to stage III patients, and the benefit was less pronounced in stage I and II patients. Our study aims to investigate the current practice of treatment and clinical outcomes in stage I high-risk endometrioid-type endometrial cancer. METHODS AND MATERIALS: A single-center retrospective study was conducted on patients with stage I high-risk endometrioid-type endometrial cancer without serous or clear cell features who have undergone hysterectomy between 1998 and 2015. Data on patients, tumor, and treatments were collected and correlated with clinical outcomes. RESULTS: A total of 1,572 patients with stage I disease were identified and 46 patients who met the inclusion criteria were selected for final analysis. The median age at diagnosis was 63 years (range, 49-86 years) and median follow-up was 5.9 years. Among the entire cohort, 40 (87.0%) patients underwent adjuvant radiation therapy, of which 36 (78.2%) patients underwent external beam radiation therapy and 4 (8.7%) patients underwent vaginal brachytherapy. Two of the 40 patients who received adjuvant radiation therapy also received adjuvant chemotherapy. Six (13.0%) patients received no adjuvant treatment. Of the 46 patients, the cumulative risk of distant recurrence was 19.6%, and only 1 patient (2.2%) recurred within pelvis (perirectal lymph node). Five-year disease-free survival and overall survival rates were 73.1% and 80.1%, respectively. CONCLUSIONS: Adjuvant radiation therapy in stage I endometrioid-type endometrial cancer patients with high-risk features resulted in high rates of locoregional disease control, and most recurrences occurred at distant sites. Effective systemic therapy may be indicated in this patient population to further reduce the risk of distant relapses and improve survival.

The Impact of High-Dose-Rate Brachytherapy: Measuring Clinical Outcomes in the Primary Treatment of Cervical Cancer.

PURPOSE: Radical concurrent chemoradiotherapy with combined external beam radiotherapy (EBRT) and brachytherapy is used to treat locally advanced cervical cancer. Our institution has transitioned to high-dose-rate (HDR) intracavitary brachytherapy (ICBT) from low-dose-rate (LDR) brachytherapy in 2008, and a review was conducted on the effect of this change on patient outcomes. METHODS AND MATERIALS: A single-arm retrospective chart review was performed on locally advanced (Fédération Internationale de Gynécologie et d'Obstétrique stage IB-IVA) patients with cervical cancer treated with combined external beam radiation therapy and HDR-ICBT with curative intent between 2008 and 2014. Clinical outcomes were evaluated, and multivariate analysis was performed to identify prognostic factors. RESULTS: Of the 76 patients selected, median age was 47.9 years and median follow-up was 5.2 years. Thirteen patients (17.1%) developed locoregional recurrence and 23 patients (30.3%) patients developed distant recurrence. Five-year progression-free survival and overall survival were 63.7% and 69.3%, respectively. A significant survival difference was found between stages (P < .001). Multivariate analysis found nodal involvement was strongly associated with poorer survival (P = .007). CONCLUSIONS: Our experience with the transition to HDR-ICBT as part of concurrent chemoradiotherapy in treatment of locally advanced cervical cancer resulted in acceptable long-term outcomes and toxicity to that of LDR brachytherapy. Potential further improvement of treatment outcomes for patients may be possible with image guided brachytherapy and the addition of effective systemic therapy.

Whole brain radiotherapy improves survival outcomes in primary CNS lymphoma patients ineligible for systemic therapy.

PURPOSE: Primary central nervous system lymphoma (PCNSL) is a very rare type of malignancy with a poor prognosis. The role of whole brain radiotherapy (WBRT) in PCNSL has been questioned due to the significant neurotoxicity and lack of convincing data for survival benefit. Even its role in a palliative setting remains to be clearly elucidated. Our study aims to investigate the benefit of WBRT in patients who are ineligible for systemic therapy. METHODS: A single-institution retrospective study was conducted on patients diagnosed with PCNSL between 2002 and 2017. Patients were excluded if they received systemic therapy or focal radiation only. Data on patient demographics and WBRT were collected and correlated with clinical outcomes. RESULTS: A total of 48 patients were selected for analysis, among which 31 (64.6%) patients received WBRT and 17 (35.4%) patients received supportive care only. Patient baseline characteristics were similar between the two groups. Median overall survival (OS) was 4.3 months among the entire cohort. WBRT was associated with improved median OS (8.0 months, range 1.4-62.3 months) compared with supportive care only (3.3 months, range 0.7-18.3 months) (HR 0.39, 95% CI 0.20-0.75, p = 0.005). Among patients who received WBRT, higher radiation dose to the whole brain was not associated with survival (p = 0.10), but higher radiation dose to the gross tumor was associated with improved survival (p = 0.007). CONCLUSION: Patients with PCNSL who are ineligible for systemic therapy may still benefit from WBRT with improvement in survival, compared with the best supportive care. Dose escalation through the addition of a gross tumor boost in these patients was associated with improved overall survival. Further studies in the prospective setting are necessary to confirm the findings from the study.

A comparison of disease recurrence between robotic versus laparotomy approach in patients with intermediate-risk endometrial cancer.

OBJECTIVE: Advances in minimally invasive surgery, particularly with robotic surgery, have resulted in improved peri-operative outcomes in patients with endometrial cancer. In addition, randomized trials have shown that addition of adjuvant radiotherapy following surgery improves loco-regional disease control among stage I intermediate-risk endometrial cancer patients. We aimed to investigate the efficacy and safety of combined treatment of robotic surgery and adjuvant radiotherapy in this patient population. METHODS: A single-center retrospective study was conducted on stage I endometrioid-type endometrial cancer patients with intermediate-risk features (<50% myometrial involvement and grade 2-3 histopathology, or >50% myometrial involvement and grade 1-2 histopathology) treated with hysterectomy and adjuvant radiotherapy between January 2010 and December 2015. Data on surgery and radiotherapy were collected and correlated with clinical and surgical outcomes using log-rank. Oncologic outcomes were then compared between robotic surgery and laparotomy. RESULTS: A total of 179 intermediate-risk endometrial cancer patients were identified, of whom 135 (75.4%) received adjuvant radiotherapy and were included in the final analysis. Median age at diagnosis was 63 years (range 40-89) and median follow-up was 4.7 years (range 1.1-8.8). Seventy-seven patients (57%) underwent robotic surgery and 58 patients (43%) underwent laparotomy. Surgical staging with lymph node dissection was performed on 79.3% of the patients. The majority of patients (79.3%) received vaginal brachytherapy as part of adjuvant radiotherapy, while 20.7% received external-beam radiotherapy. Among the entire cohort, eight (5.9%) patients recurred and all eight recurrences occurred in the robotic surgery group; no recurrence was found in the laparotomy group. This translated into 5 year disease-free survival of 100% in the laparotomy group, compared with 91.8% in the robotic surgery group (p=0.005). No difference in overall survival was found between the two groups (p=0.51). CONCLUSION: Oncologic outcomes for stage I intermediate-risk endometrial cancer treated with hysterectomy and adjuvant radiotherapy at our institution are comparable to the previously published literature. The higher recurrence rate observed with robotic surgery at our institution has not been observed previously and requires further investigation.