Patterns of Undertreatment and Overtreatment in Adjuvant Radiotherapy for Early-Stage Endometrial Cancer Based on Molecular Classification.

The quality improvement study examines the use of risk-adaptive adjuvant radiotherapy in women with non­mismatch repair deficiency endometrial cancer.

Associations Between Social Determinants of Health and Psychoneurologic Symptom Clusters in Women With Gynecologic Cancers: A Longitudinal Study.

OBJECTIVES: To evaluate the associations between social determinants of health (SDOH) and psychoneurologic symptom (PNS) clusters in women with gynecologic cancers during cancer treatment. SAMPLE & SETTING: 67 women with gynecologic cancers who received radiation therapy were assessed at baseline, six to eight weeks after treatment, and six months after treatment at oncology clinics in Georgia. METHODS & VARIABLES: Fatigue, pain, sleep disturbances, cognitive impairment, and depressive symptoms were measured to determine a PNS cluster score. Associations between SDOH and PNS cluster scores were assessed using mixed-effect models. RESULTS: Larger mean PNS cluster scores were reported in individuals with less education, lower income, and unemployment, as well as in those living in more disadvantaged neighborhoods. IMPLICATIONS FOR NURSING: Individual- and community-level SDOH and their interactions were associated with more PNS clusters. Studying SDOH at multiple levels depicts how various social disadvantages can exacerbate poor health outcomes.

Incidence and predictors of toxicity in the management of vulvar squamous cell carcinoma treated with radiation therapy.

Purpose/Objective: Given the rarity of vulvar cancer, data on the incidence of acute and late severe toxicity and patients' symptom burden from radiotherapy (RT) are lacking. Materials/Methods: This multi-center, single-institution study included patients with vulvar squamous cell carcinoma treated with curative intent RT between 2009 and 2020. Treatment-related acute and late grade ≥ 3 toxicities and late patient subjective symptoms (PSS) were recorded. Results: Forty-two patients with predominantly stage III/IV disease (n = 25, 59.5 %) were treated with either definitive (n = 25, 59.5 %) or adjuvant (n = 17, 40.5 %) external beam RT to a median dose of 64 Gy and 59.4 Gy, respectively. Five patients received a brachytherapy boost with a median total dose of 84.3 Gy in 2 Gy-equivalent dose (EQD2). Intensity-modulated RT was used in 37 (88.1 %) of patients, and 25 patients (59.5 %) received concurrent chemotherapy. Median follow-up was 27 months. Acute grade ≥ 3 toxicity occurred in 17 patients (40.5 %), including 13 (31.0 %) acute grade 3 skin events. No factors, including total RT dose (p = 0.951), were associated with acute skin toxicity. Eleven (27.5 %) patients developed late grade ≥ 3 toxicity events, including 10 (23.8 %) late grade ≥ 3 skin toxicity events. Patients with late grade ≥ 3 skin toxicity had a higher mean body-mass index (33.0 vs 28.2 kg/m2; p = 0.009). Common late PSS included vaginal pain (n = 15, 35.7 %), skin fibrosis (n = 10, 23.8 %), and requirement of long-term opiates (n = 12, 28.6 %). Conclusion: RT for vulvar cancer is associated with considerable rates of severe acute and late toxicity and PSS burden. Larger studies are needed to identify risk factors, explore toxicity mitigation strategies, and assess patient-reported outcomes.

"Did you wash your hands?": a prospective study of patient empowerment to prompt hand washing by healthcare providers.

BACKGROUND: Hand hygiene is paramount in preventing the spread of healthcare-associated infections especially during disease epidemics. Compliance rates with hand hygiene policies remain below 50% internationally and may be lower in the outpatient care setting. This study assessed the impact of the patient empowerment model on hand hygiene compliance among healthcare providers. METHODS: From October 2016 to May 2017, patients from a large ambulatory oncology centre were prospectively enrolled. Patients were instructed to observe healthcare providers for hand hygiene compliance and to remind healthcare providers where it was not observed during at least three consecutive encounters. Healthcare provider reactions to this intervention were rated by patients. Patients' hand hygiene knowledge and beliefs were objectively elicited pre and post-study. RESULTS: Thirty patients with a median age of 52 years (range 5-91) completed the study for a total of 190 healthcare provider encounters. When initial hand hygiene was not observed, patients offered a reminder in 71 (37.4%) encounters, did not offer a reminder in 73 (38.4%) encounters and forgot to offer a reminder in 24 (14.2%) encounters. Patients perceived positive or neutral reactions in 76.8% of encounters and negative or surprised reactions in 23.2% of encounters. Healthcare provider compliance improved from 11.6% to 48.9% with intervention. Patient hand hygiene knowledge improved by 16% following the study. CONCLUSIONS: Patient-empowered hand hygiene may be a useful adjunct for improving hand hygiene compliance among healthcare providers and improving patient hand hygiene knowledge, although it may confer an emotional burden on patients.

Whole-lung low-dose radiation therapy (LD-RT) for non-intubated oxygen-dependent patients with COVID-19-related pneumonia receiving dexamethasone and/or remdesevir.

BACKGROUND: Low-dose radiotherapy (LD-RT) has produced anti-inflammatory effects in both animal models and early human trials of COVID-19-related pneumonia. The role of whole-lung LD-RT within existing treatment paradigms merits further study. METHODS: A phase II prospective trial studied the addition of LD-RT to standard drug treatments. Hospitalized and oxygen-dependent patients receiving dexamethasone and/or remdesevir were treated with 1.5 Gy whole-lung LD-RT and compared to a blindly-matched contemporaneous control cohort. RESULTS: Of 40 patients evaluated, 20 received drug therapy combined with whole-lung LD-RT and 20 without LD-RT. Intubation rates were 14% with LD-RT compared to 32% without (p = 0.09). Intubation-free survival was 77% vs. 68% (p = 0.17). Biomarkers of inflammation (C-reactive protein, p = 0.02) and cardiac injury (creatine kinase, p < 0.01) declined following LD-RT compared to controls. Mean time febrile was 1.4 vs 3.3 days, respectively (p = 0.14). Significant differences in clinical recovery (7.5 vs. 7 days, p = 0.37) and radiographic improvement (p = 0.72) were not detected. On subset analysis, CRP decline following LD-RT was predictive of recovery without intubation compared to controls (0% vs. 31%, p = 0.04), freedom from prolonged hospitalizations (21+ days) (0% vs. 31%, p = 0.04), and decline in oxygenation burden (56% reduction, p = 0.06). CRP decline following 1st drug therapy was not similarly predictive of outcome in controls (p = 0.36). CONCLUSIONS: Adding LD-RT to standard drug treatments reduced biomarkers of inflammation and cardiac injury in COVID-19 patients and may have reduced intubation. Durable CRP decline following LD-RT predicted especially favorable recovery, freedom from intubation, reduction in prolonged hospitalization, and reduced oxygenation burden. A confirmatory randomized trial is now ongoing. CLINICAL TRIAL REGISTRATION: NCT04366791.

The Effect of Adjuvant Pelvic Radiotherapy on Distant Metastasis for Uterine Carcinosarcoma.

BACKGROUND: Uterine carcinosarcomas (UCS) are rare tumors that carry a poor prognosis and high recurrence rate. Standard treatment consists of surgical resection and chemotherapy, though the benefit of adjuvant radiotherapy (RT) has yet to be determined. This study assessed survival rates between patients with UCS who underwent surgical resection alone and patients who underwent combinations of surgery, chemotherapy, and RT. MATERIALS AND METHODS: We conducted a retrospective review of all patients who underwent surgical resection for UCS between 1993 and 2011 at a single institution. We assessed 3-year disease-free survival, locoregional recurrence-free survival, distant metastases-free survival (DMFS), and overall survival rates and utilized Kaplan-Meier modeling to analyze differences between UCS treatment modalities. RESULTS: Twenty-four patients underwent UCS surgical resection between 1993 and 2011. The mean age was 61 (range: 39 to 75 y). Of these patients, 100% (n=24) underwent surgical resection, 25% (n=6) underwent surgery and adjuvant chemotherapy, 29% (n=7) underwent surgery and adjuvant RT, and 33% (n=8) underwent surgery and adjuvant chemotherapy and RT. At 3 years median follow, there was no significant difference in overall survival between treatment modalities. The addition of radiation therapy conferred increased DMFS in patients undergoing surgery irrespective of adjuvant chemotherapy (44% vs. 83%, P=0.0211).In patients receiving adjuvant chemotherapy, the significant increase in DMFS persisted with the addition of RT (P=0.0310). Lymph node involvement (n=8) was associated with a lower locoregional recurrence-free survival (38% vs. 92%, P=0.0029). CONCLUSIONS: RT may offer a potential benefit in reducing the rate of distant metastases, though there were no statistically significant improvements in survival metrics.

A Multi-atlas Approach for Active Bone Marrow Sparing Radiation Therapy: Implementation in the NRG-GY006 Trial.

PURPOSE: Sparing active bone marrow (ABM) can reduce acute hematologic toxicity in patients undergoing chemoradiotherapy for cervical cancer, but ABM segmentation based on positron emission tomography/computed tomography (PET/CT) is costly. We sought to develop an atlas-based ABM segmentation method for implementation in a prospective clinical trial. METHODS AND MATERIALS: A multiatlas was built on a training set of 144 patients and validated in 32 patients from the NRG-GY006 clinical trial. ABM for individual patients was defined as the subvolume of pelvic bone greater than the individual mean standardized uptake value on registered 18F-fluorodeoxyglucose PET/CT images. Atlas-based and custom ABM segmentations were compared using the Dice similarity coefficient and mean distance to agreement and used to generate ABM-sparing intensity modulated radiation therapy plans. Dose-volume metrics and normal tissue complication probabilities of the two approaches were compared using linear regression. RESULTS: Atlas-based ABM volumes (mean [standard deviation], 548.4 [88.3] cm3) were slightly larger than custom ABM volumes (535.1 [93.2] cm3), with a Dice similarity coefficient of 0.73. Total pelvic bone marrow V20 and Dmean were systematically higher and custom ABM V10 was systematically lower with custom-based plans (slope: 1.021 [95% confidence interval (CI), 1.005-1.037], 1.014 [95% CI, 1.006-1.022], and 0.98 [95% CI, 0.97-0.99], respectively). We found no significant differences between atlas-based and custom-based plans in bowel, rectum, bladder, femoral heads, or target dose-volume metrics. CONCLUSIONS: Atlas-based ABM segmentation can reduce pelvic bone marrow dose while achieving comparable target and other normal tissue dosimetry. This approach may allow ABM sparing in settings where PET/CT is unavailable.

Comparison of vaginal microbiota in gynecologic cancer patients pre- and post-radiation therapy and healthy women.

BACKGROUND: While the importance of commensal microbes in vaginal health is well appreciated, little is known about the effects of gynecological cancer (GynCa) and radiation therapy (RT) on the vaginal microbiome (VM) of postmenopausal women. METHODS: We studied women with GynCa, pre- (N = 65) and post-RT (N = 25) and a group of healthy controls (N = 67) by sequencing the V4 region of the 16S rRNA gene from vaginal swabs and compared the diversity and composition of VMs between the three groups accounting for potential confounding factors in multivariate analysis of variance. RESULTS: Comparisons of cancer vs healthy groups revealed that Lactobacillus and Bifidobacterium have significantly higher relative abundance in the healthy group, while the cancer group was enriched in 16 phylogroups associated with bacterial vaginosis (BV) and inflammation, including Sneathia, Prevotella, Peptoniphilus, Fusobacterium, Anaerococcus, Dialister, Moryella, and Peptostreptococcus. In our sample, RT affected the α-diversity and correlated with higher abundance of typically rare VM species, including several members of the Lacnospiraceae family, a taxon previously linked to vaginal dysbiosis. In addition to cancer and treatment modalities, age and vaginal pH were identified as significant parameters that structure the VM. CONCLUSIONS: This is among the first reports identifying VM changes among postmenopausal women with cancer. RT alone seems to affect several phylogroups (12 bacterial genera), while gynecological cancer and its treatment modalities are associated with even greater significant shifts in the vaginal microbiota including the enrichment of opportunistic bacterial pathogens, which warrants further attention.

Radiation Therapy for Benign Disease: Arteriovenous Malformations, Desmoid Tumor, Dupuytren Contracture, Graves Ophthalmopathy, Gynecomastia, Heterotopic Ossification, Histiocytosis.

Although the use of ionizing radiation in malignant conditions has been well established, its application in benign conditions has not been fully accepted and has been inadequately recognized by health care providers outside of radiation therapy. Most frequently, radiation therapy in these benign conditions is used along with other treatment modalities, such as surgery, in instances where the condition causes significant disability or could even lead to death. Radiation therapy can be helpful for inflammatory/proliferative disorders. This article discusses the current use of radiation therapy in some of the more common benign conditions.

Radiation Therapy for Benign Disease: Keloids, Macular Degeneration, Orbital Pseudotumor, Pterygium, Peyronie Disease, Trigeminal Neuralgia.

Although the use of ionizing radiation on malignant conditions has been well established, its application on benign conditions has not been fully accepted and has been inadequately recognized by health care providers outside of radiation therapy. Most frequently, radiation therapy in these benign conditions is used along with other treatment modalities, such as surgery, when the condition causes significant disability or could even lead to death. Radiation therapy can be helpful for inflammatory/proliferative disorders. This article discusses the present use of radiation therapy for some of the most common benign conditions.

Clinical Outcomes of Spatially Fractionated GRID Radiotherapy in the Treatment of Bulky Tumors of the Head and Neck.

Objectives The clinical outcomes of patients treated with spatially fractionated GRID radiotherapy (SFGRT) for bulky tumors of the head and neck at a single institution were evaluated retrospectively. Endpoints of interest included tumor response, symptom improvement, treatment tolerance, and adverse events. Methods Institutional review board approval was obtained prior to study initiation. The institutional database was queried for patients with tumors of the head and neck treated with SFGRT between August 2007 and April 2015. Medical records of identified patients were reviewed for treatment details and clinical endpoints of interest. SFGRT was delivered in one fraction of 15 gray (Gy) or 20 Gy; 6 megavolt (MV) or 18 MV photon beams were passed through a multileaf collimator (MLC)-based or brass GRID template. All patients had a planned course of conventionally-fractionated external beam radiotherapy (EBRT) to begin on the day following SFGRT delivery. Results Twenty-one consecutive patients meeting study criteria were identified. The most common tumor histology was squamous cell carcinoma. Median patient age was 59 years (range 13 - 83 years); median maximum tumor dimension was 9.5 centimeters (cm) (range 5.0 - 25.0 cm). Fifteen patients (71.4%) completed their full course of EBRT. Twelve patients were treated with palliative intent for local tumor symptoms, of which 54.5% experienced some degree of symptom improvement. Of nine patients treated with curative intent, 44.4% achieved a clinical complete response (CR). Concurrent chemotherapy was administered in 12 patients, with all patients being treated having definitively received chemotherapy. Radiation Therapy Oncology Group (RTOG) grade three or higher skin toxicity occurred in five patients; no grade five events were reported. Conclusions Our institutional experience suggests that SFGRT is a feasible treatment option for the palliative or definitive management of large tumors of the head and neck. In combination with EBRT, SFGRT can provide timely symptom management and improve patient quality of life in the palliative setting. In the definitive setting, the addition of chemotherapy to SFGRT and EBRT can result in an excellent clinical response. Treatment toxicity was found to be within an acceptable range. When considering SFGRT for patients with these challenging presentations, careful patient selection is needed to identify those who will likely tolerate a full course of EBRT following SFGRT, as these patients are most likely to receive maximal benefit from SFGRT treatment. More data on the feasibility and efficacy of this radiation modality will be helpful for continued optimization of SFGRT delivery and patient selection.

Treatment and Outcomes of Primary Urethra Cancer.

BACKGROUND: Urethral cancer is a rare malignancy, representing <1% of all malignancies. Optimal management, due to its rarity, presents as a treatment dilemma for physicians. There is a lack of consensus regarding treatment as large randomized trials cannot be performed; thus, optimal management decisions rely on study of retrospective cases. This is a review of our institutional experience with urethral cancer treated with various treatment modalities. METHODS: A retrospective chart review was performed on 31 patients treated for primary cancer of the urethra from 1958 to 2008. The patients were stratified by sex, histologic type, stage, date of diagnosis, type of treatment, and last follow-up. Early stage cases were designated as Tis-T2N0M0 and advanced cases were designated as T3-4, N+ or M+. Analysis was performed based on clinical stage, treatment modalities and outcomes. RESULTS: Fourteen early stage cases and 17 advanced stage cases of urethral cancer were analyzed. The majority of early stage cases occurred in men (M:F=8:6) and the majority of advanced stage cases occurred in women (M:F=5:12). The most common histology was squamous cell carcinoma for both early and advanced stage cases. Surgery was the preferred modality of treatment for early stage cases (surgery used in 13 cases vs. chemo/radiotherapy used in 1 case) while for advanced cases, radiation ±chemotherapy was commonly used. Overall survival for this series was 45% at mean follow-up of 7 years. Eight of the 14 cases of early stage cancer remained disease free at last follow-up. Comparatively, only 5 of 17 with advanced cancers had no apparent disease at last follow-up. All but one of those patients were treated with combined modality therapy. CONCLUSIONS: Patients with early stage urethral cancers do well with single modality therapy, whereas patients who present with advanced cancers may benefit from combined modality therapy. More extensive study is required to recommend a particular treatment protocol. However, in this rare malignancy, institutional experiences provide the best evidence currently due to the lack of multi-institutional trials.

Persistent Disparities in Hispanics with Cervical Cancer in a Major City.

OBJECTIVES: Despite an overall improvement in cervical cancer screening, incidence, and mortality rates for minorities in the USA, regional differences in screening and stage at presentation have been observed. This study evaluated cervical cancer disparities in a predominately Hispanic population treated in a major treatment center in San Antonio, Texas. METHODS AND MATERIALS: Data on 446 patients with cervical cancer treated between 2000 and 2011 at the Cancer Therapy and Research Center in San Antonio, Texas, were reviewed. Sufficient information was obtained on 319 patients and was compared with the Surveillance, Epidemiology, and End Results (SEER) data. RESULTS: Of 319 patients treated for cervical cancer between 2000 and 2011, 209 were Hispanics and 110 were Whites (82), Blacks (20), Asians (7), and others (1). The median and mean ages at diagnosis were 47 and 49, respectively. Only 36 % were known to have screening Pap tests prior to diagnosis, of which only 24 had yearly Pap tests. Forty-two patients (20 %) of those with no known screening Pap tests presented with stage IV disease at diagnosis (vs. 3 % of those with known Pap tests). Among the Hispanics, 68 % presented with regional disease (vs. 37 % SEER) and 46 % were stage III or higher disease, with stage IIIB accounting for 30 % of total. Although the overall age-adjusted death rates were higher in Hispanics due to a higher percentage of more advanced disease, survival rates appear similar, stage for stage, to the SEER data. CONCLUSION: Even in a major city, Hispanics often present with more advanced cervical cancer than the general population. In order to minimize the cervical cancer disparities, efforts and strategies are needed to study the cultural and locale effects and to implement preventive measures and adaptive health education.

Prescribed and Measured Dose Differences for an AP-PA TBI Protocol with Compensation Filter and Ergonomic Patient Support.

INTRODUCTION: A treatment scheme is presented for clinical applications of total body radiation using 6 MV photons. METHODS: The two-field technique, anteroposterior (AP) and posteroanterior (PA), was applied. In vivo dose verification with TLD-100 dosimeters was developed during the first treatment sessions. Dosimetry was performed in several anatomical regions such as head, shoulder, thorax, abdomen, hip, thigh, knee, and ankle in 13 patients as preconditioning for bone marrow transplantation. A prescribed dose of 100 cGy was considered at the level of the patient's coronal plane. Values with least differences between measured and prescribed dose were obtained for the shoulder. RESULTS: Standard deviation percentages of 0.3% and 2.6% were recorded between these doses for AP and PA, respectively. There were larger differences for other contours. In general, a measured dose less than the prescribed dose was observed in all the contours. CONCLUSION: Differences between prescribed and measured doses showed in this study can contribute to a required understanding about the accurate doses in AP-PA total body irradiation (TBI) treatments.

p53-based strategy to reduce hematological toxicity of chemotherapy: A proof of principle study.

p53 activation is a primary mechanism underlying pathological responses to DNA damaging agents such as chemotherapy and radiotherapy. Our recent animal studies showed that low dose arsenic (LDA)-induced transient p53 inhibition selectively protected normal tissues from chemotherapy-induced toxicity. Study objectives were to: 1) define the lowest safe dose of arsenic trioxide that transiently blocks p53 activation in patients and 2) assess the potential of LDA to decrease hematological toxicity from chemotherapy. Patients scheduled to receive minimum 4 cycles of myelosuppressive chemotherapy were eligible. For objective 1, dose escalation of LDA started at 0.005 mg/kg/day for 3 days. This dose satisfied objective 1 and was administered before chemotherapy cycles 2, 4, and 6 for objective 2. p53 level in peripheral lymphocytes was measured on day 1 of each cycle by ELISA assay. Chemotherapy cycles 1, 3, and 5 served as the baseline for the subsequent cycles of 2, 4, and 6 respectively. If p53 level for the subsequent cycle was lower (or higher) than the baseline cycle, p53 was defined as "suppressed" (or "activated") for the pair of cycles. Repeated measures linear models of CBC in terms of day, cycle, p53 activity and interaction terms were used. Twenty-six patients treated with 3 week cycle regimens form the base of analyses. The mean white blood cell, hemoglobin and absolute neutrophil counts were significantly higher in the "suppressed" relative to the "activated" group. These data support the proof of principle that suppression of p53 could lead to protection of bone marrow in patients receiving chemotherapy. This trial is registered in ClinicalTrials.gov. Identifier: NCT01428128.

Measurement of neutron dose equivalent outside and inside of the treatment vault of GRID therapy.

PURPOSE: To evaluate the neutron and photon dose equivalent rates at the treatment vault entrance (Hn,D and HG), and to study the secondary radiation to the patient in GRID therapy. The radiation activation on the grid was studied. METHODS: A Varian Clinac 23EX accelerator was working at 18 MV mode with a grid manufactured by .decimal, Inc. The Hn,D and HG were measured using an Andersson-Braun neutron REM meter, and a Geiger Müller counter. The radiation activation on the grid was measured after the irradiation with an ion chamber γ-ray survey meter. The secondary radiation dose equivalent to patient was evaluated by etched track detectors and OSL detectors on a RANDO(®) phantom. RESULTS: Within the measurement uncertainty, there is no significant difference between the Hn,D and HG with and without a grid. However, the neutron dose equivalent to the patient with the grid is, on average, 35.3% lower than that without the grid when using the same field size and the same amount of monitor unit. The photon dose equivalent to the patient with the grid is, on average, 44.9% lower. The measured average half-life of the radiation activation in the grid is 12.0 (± 0.9) min. The activation can be categorized into a fast decay component and a slow decay component with half-lives of 3.4 (± 1.6) min and 15.3 (± 4.0) min, respectively. There was no detectable radioactive contamination found on the surface of the grid through a wipe test. CONCLUSIONS: This work indicates that there is no significant change of the Hn,D and HG in GRID therapy, compared with a conventional external beam therapy. However, the neutron and scattered photon dose equivalent to the patient decrease dramatically with the grid and can be clinical irrelevant. Meanwhile, the users of a grid should be aware of the possible high dose to the radiation worker from the radiation activation on the surface of the grid. A delay in handling the grid after the beam delivery is suggested.

Merkel cell carcinoma.

Merkel cell carcinoma (MCC) is a rare, clinically aggressive cutaneous neuroendocrine neoplasm with a high mortality rate. Though the etiology is not precisely known, Merkel cell polyomavirus DNA has been found recently in a large percentage of MCC tumors. Other suggested risk factors include sun exposure, immunosuppression, and a history of prior malignancy. Work up of patients with MCC most notably includes nodal staging via clinical examination or sentinel lymph node biopsy. The prognosis for most patients with MCC is poor, and the rarity of MCC precludes the prospective, randomized clinical trials necessary to elucidate optimum treatment protocols. Most published data support the use of a multimodality approach centered around surgical excision with negative margins, sentinel lymph node biopsy to establish the presence or absence of nodal metastases, adjuvant radiothearpy to decrease the risk of recurrence, and systemic chemotherapy in the case of widespread disease.

Radiotherapy for thymic neoplasms.

The role of radiotherapy in the treatment of thymoma and thymic carcinoma has been evaluated by many investigators over the past two decades. The low incidence of these neoplasms has limited most published studies to small series spanning long time intervals or population-based studies. The exact indications and protocols for the use of radiotherapy as a part of the multidisciplinary approach to thymoma and thymic carcinoma are still unclear. However, a review of recent literature shows potential benefits for certain patients based on stage and grade of disease as well as the extent of surgical resection.