Received Radiation Therapy Research Articles

Clinical Profile and Treatment Outcomes of Malignant Mixed Mullerian Tumors of the Uterus: A Single-Center Experience.

Background A malignant mixed Mullerian tumor (MMMT), otherwise known as carcinosarcoma, is a rare and aggressive malignancy involving the uterus. Despite aggressive treatment, they have poor outcomes. We performed this study to analyze the clinical profile, prognostic features, and treatment outcomes of patients treated for MMMT of the uterine corpus in our center. Methodology A study sample from a database of patients treated at a tertiary care center in South India between January 2015 and December 2019 was analyzed retrospectively. A total of 29 non-metastatic patients were included in the study. The diagnosis of MMMT was confirmed by a pre-operative biopsy specimen or endometrial curettage. Information regarding the patient, tumor characteristics, details of the surgery, adjuvant therapy, and follow-up details were collected retrospectively. Disease-free survival (DFS) and overall survival (OS) were plotted using the Kaplan-Meier method, and the log-rank test was used to identify any significant prognostic factor. Statistical analyses were performed using IBM SPSS software, version 21 (IBM Corp., Armonk, NY). Results The population's median age was 60 years (interquartile range (IQR): 52-65). The homologous type was the most common pathology seen in 21 patients. The median size of the tumor was 7 centimeters (cm) (IQR: 6-10). Around two-thirds of the patients received adjuvant radiation therapy. Paclitaxel and carboplatin-based adjuvant chemotherapy were used in 60% of the patients. Nearly 90% of the recurrences were distant recurrences. During the follow-up, 17 patients developed a recurrence. The median DFS was 12 months (95% CI: 7.7-16.2). The median OS was 26 months (95% CI: 10.6-41.3). The three-year OS rate was 42%. Patients with an age >60 years had a median overall survival of 11 months, compared to 37 months for patients <60 years (p = 0.026). The median overall survival of patients with tumor sizes >10 cm was 12.5 months, and it was 35 months when the tumor size was less than 10 cm (p = 0.03). Patients receiving radiotherapy (RT) had an improved survival (39 months) compared to those who did not receive RT (12.5 months) (p = 0.046). The median overall survival for patients after the recurrence was 12 months. As most patients were elderly with an Eastern Cooperative Oncology Group (ECOG) performance status of two at baseline, only a few patients were fit for second-line chemotherapy. Conclusion A malignant mixed Mullerian tumor is an aggressive tumor of the uterine corpus with poor survival rates. Surgical resection remains the mainstay of treatment. Adjuvant radiation therapy improves survival. The age of the patient, myometrium invasion, tumor size, and positive peritoneal cytology were found to be prognostic factors.

RNA N6-methyladenosine modification-based biomarkers for absorbed ionizing radiation dose estimation

Radiation triage and biological dosimetry are critical for the medical management of massive potentially exposed individuals following radiological accidents. Here, we performed a genome-wide screening of radiation-responding mRNAs, whose N6-methyladenosine (m6A) levels showed significant alteration after acute irradiation. The m6A levels of three genes, Ncoa4, Ate1 and Fgf22, in peripheral blood mononuclear cells (PBMCs) of mice showed excellent dose-response relationships and could serve as biomarkers of radiation exposure. Especially, the RNA m6A of Ncoa4 maintained a high level as long as 28 days after irradiation. We demonstrated its responsive specificity to radiation, conservation across the mice, monkeys and humans, and the dose-response relationship in PBMCs from cancer patients receiving radiation therapy. Finally, NOCA4 m6A-based biodosimetric models were constructed for estimating absorbed radiation doses in mice or humans. Collectively, this study demonstrated the potential feasibility of RNA m6A in radiation accidents management and clinical applications.

Economic Evaluation of a Nonmedical Financial Assistance Program on Missed Treatment Appointments Among Adults With Cancer.

We retrospectively evaluated the clinical and economic impact of a program providing nonmedical financial assistance on missed treatment appointments among patients receiving cancer treatment at a large, Southeastern public hospital system. We used patient electronic health records, program records, and cancer registry data to examine the impact of the program on rates of missed (or no-show) radiation therapy and infusion chemotherapy/immunotherapy appointments in the 180 days after treatment initiation. We used propensity weighting to estimate the effect of the program, stratified by treatment appointment type (radiation therapy, infusion chemotherapy/immunotherapy). We developed a decision tree-based economic model to conduct a cost-consequence analysis from the health system perspective in a hypothetical cohort over a 6-month time horizon. Of 1,347 patients receiving radiation therapy between 2015 and 2019, 53% (n = 715) had ≥1 no-shows and 28% (n = 378) received program assistance. Receipt of any assistance was associated with a 2.1 percentage point (95% CI, 0.6 to 3.5) decrease in the proportion of no-shows, corresponding to a 51% decrease in the overall mean no-show proportion. Under the current funding model, the program is estimated to save the health system $153 in US dollars per missed appointment averted, relative to not providing nonmedical financial assistance. Of the 1,641 patients receiving infusion chemotherapy/immunotherapy, 33% (n = 541) received program assistance, and only 14% (n = 223) had ≥1 no-shows. The financial assistance program did not have a significant effect on no-show proportions among infusion visits. This study used a novel approach to retrospectively evaluate a nonmedical financial assistance program for patients undergoing active cancer treatment. Findings support investment in programs that address patients' nonmedical financial needs, particularly for those undergoing intensive radiation therapy.

Comparison of the Efficacy of Different Doses of Intensity-modulated Radiation Therapy After Breast-conserving Surgery for Early-stage Breast Cancer

Objective — To investigate the efficacy of different doses of intensity modulated radiation therapy in patients with early breast cancer after breast conserving surgery in order to provide more accurate treatment guidelines for clinical practice to further improve treatment outcomes and quality of life in breast cancer patients. Methods — The main objective of this study was to evaluate the effects of different radiotherapy regimens after breast conserving surgery for early stage breast cancer. The study included 96 patients with early-stage breast cancer who were treated in our oncology department between January 2020 and May 2021. Patients were self-divided into group A and Group B by double-blind method, with 48 patients in each group. Group A received radiation therapy of 50Gy/25Fx for the whole breast after surgery, and an additional dose of 60Gy/25Fx was added to irradiate the tumor bed. Group B received whole breast radiation therapy of 50Gy/25Fx and tumor bed push of 10Gy/5Fx at the same time. The study will compare the differences between the two groups in treatment outcomes, three-year survival, and various adverse events that occur within six months of radiotherapy. Results — When comparing the two groups with different doses of IMRT, the authors focused on the difference in the percentage of the combined volume of prescription dose exposure above the percentage measurement line and the target dose uniformity index. The results showed very significant statistical differences between the two groups for both measures. In addition, it is worth noting that the probability of adverse reactions in group B patients exceeded that in group A, with a statistically significant difference. Conclusion — For patients undergoing breast conserving surgery for early stage breast cancer, receiving radiation therapy with a total dose of 60Gy can significantly improve treatment outcomes. Compared with other dosing regimens, the use of 60Gy intensity modulated radiation therapy can significantly reduce the incidence of adverse reactions while achieving the same therapeutic effect.

Probability of a high recurrence score for breast cancer on the Oncotype DX test in males: a case series

Abstract Introduction: Male breast cancer (MBC) is a rare disease that accounts for 1% of breast cancers. The Oncotype DX test (a genomic signature that assesses the expression of 21 genes to estimate the recurrence score [RS]) has been widely used in MBC to select patients for adjuvant chemotherapy. Objective: To describe 5 cases of MBC in which a nomogram was used to predict the probability of having a high Oncotype DX score for breast cancer and the need to perform genomic signature. Materials and methods: Case series study in which five patients with MBC treated between 2007 and 2020 at a cancer institution in Teresina (Brazil) were included. A nomogram was performed to evaluate five clinical and pathological variables (age, body size, tumor size, grade, recurrence score status, and histologic type of carcinoma). Case series: The mean age of the patients at diagnosis was 69 years (mean tumor size: 2.6cm). All patients received hormone therapy with tamoxifen, three received chemotherapy, and one received radiation therapy after breast surgery (mastectomy). During a median follow-up period of 88 months, one case had a recurrence (bone metastasis). Based on the nomogram results, two patients had a high probability of a high RS (36% and 45%) and only one patient (case 3) underwent Oncotype DX testing (RS: 20). Conclusions: In the present series of five cases, based on the nomogram results, only two patients (cases 3 and 4) had a high probability of a high Oncotype DX recurrence score; however, due to financial constraints, this test was only performed on one of these two patients. The patient who underwent the test (case 3) did not receive adjuvant chemotherapy and remained alive with bone metastases until the end of the follow-up period. Conversely, the patient who could not undergo the examination (case 4) received adjuvant chemotherapy and was alive without any signs of disease.

Severe Oral Mucositis After Intensity-Modulated Radiation Therapy for Head and Neck Cancer

Oral mucositis (OM) is a common and debilitating adverse effect observed in patients with head and neck cancer (HNC) receiving radiation therapy (RT). Previous studies examining associations between OM and clinical outcomes were performed in the era of 3-dimensional conformal RT planning with low rates of concurrent chemotherapy, and thus may not reflect current practice. To prospectively assess patient-reported OM and identify its associations with clinical outcomes and quality of life. This cohort study performed at a single institution included 702 consecutive patients who underwent definitive or adjuvant intensity-modulated RT (IMRT) for primary HNC from February 9, 2015, to May 27, 2022. Data were analyzed from November 28, 2022, to August 18, 2023. Severity of OM was assessed based on highest reported mouth and throat soreness (MTS) score during radiotherapy according to the Oral Mucositis Weekly Questionnaire-Head and Neck Cancer survey, which was administered weekly during IMRT. Linear mixed models were used to compare mean MTS scores grouped by disease site and chemotherapy regimen. Fisher exact tests and 1-way analysis of variance tests were performed to identify associations between severity of OM and clinical outcomes. Among 576 eligible patients, the median age was 62.5 (IQR, 56.3-69.1) years, and 451 patients (78.3%) were men. In terms of race and ethnicity, 6 patients (1.0%) were American Indian or Alaska Native; 2 (0.3%), Asian; 31 (5.4%), Black; 8 (1.4%), Hispanic or Latino; 509 (88.4%), White; and 28 (4.9%), unknown. The most common treatment site was oropharynx (268 [46.5%]), and most patients received concurrent chemotherapy (464 [80.6%]). By the end of treatment, 360 patients (62.5%) developed severe OM and 568 (98.6%) developed some degree of OM. Linear mixed models found no significant differences in OM between HNC disease sites. Groups with greater highest severity of OM reported had higher rates of measured outcomes (listed respectively by MTS score 0, 1, 2, 3, and 4): feeding tube placement (0%, 3.6% [2 of 56], 6.6% [10 of 152], 14.7% [40 of 272], and 21.6% [19 of 88]; P = .001), hospitalization (12.5% [1 of 8], 10.7% [6 of 56], 15.1% [23 of 152], 23.9% [65 of 272], and 28.4% [25 of 88]; P = .02), opiate use (0%, 19.6% [11 of 56], 42.8%[65 of 152], 61.4% [167 of 272], and 64.8% [57 of 88]; P < .001) and experienced greater weight loss (median, -0.7 [IQR, -1.7 to -0.4] kg; median, 3.9 [IQR, 1.1 to 6.1] kg; median, 5.0 [IQR, 2.2 to 7.7] kg; median, 4.7 [IQR, 2.1 to 7.7] kg; and median, 7.7 [IQR, 2.8 to 10.6] kg; P < .001). In this cohort study of patients with HNC, 62.5% developed severe OM. Higher severity of OM was associated with feeding tube placement, hospitalization, opiate use, and weight loss. Improvements in OM prevention and management are needed.

SAT572 Concomitant Metastatic Hurthle Cell Carcinoma And Rectal Cancer, Challenges In Diagnosis And Management

Abstract Disclosure: D. Khurram: None. R. Pansare: None. S.L. Mokshagundam: None. Hurthle cell carcinomas (HCC) are aggressive tumors and account for 5% of follicular cell thyroid malignancies. Tumor size, extra-thyroid extension and distant metastases indicate poor prognosis. 20-30% of HCCs have mets at initial diagnosis, frequent sites being lungs and bones. Metastatic HCCs are exceedingly difficult to manage. Detecting two primary cancers concomitantly is uncommon and poses additional challenges in diagnosis and management. We present an interesting case of HCC with mets to the manubrium, vertebrae, lungs and concomitant rectal adenocarcinoma. A 69-year-old male had MRI spine for back pain which showed multiple lytic osseous lesions within T3 and L1 vertebrae. Further imaging revealed a large lesion in the manubrium. Manubrial mass biopsy was positive for poorly differentiated carcinoma, immunohistochemical staining for CAM5.2, cytokeratin, CD 138, CD56 and TTF-1 (weak). He underwent 6 cycles of palliative chemotherapy with carboplatin and Taxol for carcinoma of unknown origin. PET scan following chemotherapy showed a large heterogenous thyroid mass with intense FDG uptake, along with a suspicious rectal mass. Left thyroid nodule FNA reported Bethesda IV follicular neoplasm, Hurthle cell type. Rectal mass biopsy reported moderately differentiated adenocarcinoma. Histology after total thyroidectomy showed unifocal oncocytic HCC, with lymphovascular invasion but no extrathyroidal extension. Molecular markers showed low TMB, stable microsatellite status, negative PDL-1, negative NTRK fusion and positive ATM E839. He received suppressive dose levothyroxine. Radio-iodine ablation was postponed owing to prioritization of radiation therapy for rectal cancer. Thyroglobulin level increased from 53 ng/ML to 216 ng/ML. He received 149 milli Curies of I131 after Thyrogen stimulation. There was mild radioiodine uptake in the thyroid bed, but the metastatic lesions were not radioiodine avid. Follow-up scans showed multiple bilateral pulmonary nodules with worsening osseous mets. Endoscopic biopsy was consistent with HCC, TTF-1 and PAX8 positive. He was started on Lenvatinib but developed diarrhea, hence switched to Pembrolizumab. Thyroglobulin level improved on Pembrolizumab but was complicated by adrenal insufficiency. For rectal cancer, he received radiation therapy and capecitabine. Our case is interesting for several reasons. Firstly, although bone mets are commonly seen in HCC, manubrial mets, especially as the presenting feature is rare. Secondly, concomitant rectal cancer delayed the treatment of the thyroid cancer. Thirdly, there is no major consensus regarding management of HCC, especially metastatic HCC. HCCs are often not radioactive iodine avid. Combination therapy with Lenvatinib and Pembrolizumab is currently under trial for aggressive thyroid malignancy. It will be interesting to follow the clinical outcomes in this individual. Presentation: Saturday, June 17, 2023

SAT563 Follicular Thyroid Cancer Masquerading as Chest Wall Mass With an Aggressive Course

Abstract Disclosure: I. Goyal: None. E. Punni: None. L. Adhikari: None. Introduction:Follicular thyroid cancers (FTC) are more aggressive than papillary thyroid cancer and usually have more advanced tumor stage at the time of presentation. Musculoskeletal metastases are rare though, but when present can cause various complications like pathological fractures and nerve compression. Clinical case:A 75-year-old female was seen in orthopedics clinic for a left infraclavicular chest wall mass. MRI chest showed a large destructive mass invading the manubrium. Biopsy showed follicular cells consistent with ectopic thyroid tissue. CT neck/chest showed 2x1.8 cm right thyroid lobe nodule and left sternoclavicular joint metastasis. She underwent total thyroidectomy and resection of portions of manubrium, left clavicle and left 1st and 2nd rib. Pathology showed FTC in right thyroid lobe, measuring 2.6 cm in greatest dimension with angioinvasion, and FTC of manubrium, adjacent connective tissue and sternoclavicular joint and ribs, measuring 6.3 cm in greatest dimension. Pathological TNM staging was pT2N0M1. Her 6-week post-op thyroglobulin (Tg) level was 28.7 ng/mL (Beckman Coulter Immunometric Assay, reference value &amp;lt;0.1 athyrotic). She was started on levothyroxine supplementation to achieve a TSH &amp;lt;0.01 uIu/mL. She was subsequently treated with 200 mCi of radio-active iodine (RAI) as adjuvant therapy. Post-therapy whole body scan showed increased activity in the right strap muscle and iodine-avid osseous metastasis in right hemisacrum. She further received radiation therapy to neck and sternal regions, and the right sacroiliac joint. Following this, patient was monitored with serial Tg panel and neck ultrasound (US). Her initial post-op US neck showed a soft tissue fullness in right thyroidectomy bed, concerning for residual disease but this was no longer seen after 3 months. Her Tg level downtrended from 28.7 ng/mL to 12.6 ng/mL and further to 1.8 ng/mL at 1-year follow-up. However, her course was complicated by development of several oral ulcers resulting from high-dose RAI therapy which were treated symptomatically with hydration, topical analgesics and Listerine mouth washes. The patient reported ongoing bowel incontinence since her initial cancer diagnosis. MRI pelvis showed rim-enhancing 4.5cm lesion centered at right sacral ala and extending into adjacent S1/S2 neural foramina. She was re-referred for palliative radiation therapy.Conclusion:This case of FTC is unique due to its uncommon initial presentation. Skeletal metastases to sacrum resulted in bowel incontinence in our patient. When present, skeletal metastases need treatment with high-dose (200 mCi) RAI. RAI therapy can cause xerostomia, hypogeusia and sialadenitis due to reductions in salivary flow. Clinicians should be aware of the early and late-onset complications of RAI therapy, discuss these with the patient before therapy and manage the complications adequately if these occur. Presentation Date: Saturday, June 17, 2023

AGE, EDUCATIONAL LEVEL, ANXIETY LEVEL, AND SLEEP PATTERNS OF CERVICAL CANCER PATIENTS UNDERGOING EXTERNAL RADIOTHERAPY TREATMENT

Background: Treatment for cervical cancer includes surgery, radiotherapy or chemotherapy. Quite a lot of cancer sufferers who go to hospitals receive radiation therapy. The diagnosis and treatment of cervical cancer is always accompanied by psychological challenges, namely anxiety, which causes sleep pattern disturbances in the patient. Objective: This study aimed to determine the relationship between age, education level, anxiety level, and sleep patterns in cervical cancer patients undergoing external radiotherapy treatment. Method: The research method used a cross sectional approach design by collecting data on independent variables and dependent variables. The sampling technique in this research used Total Sampling. The sample consisted of 20 cervical cancer respondents who underwent external radiation, then the data collected was processed using the Spearmen Rho test. Results: Based on the research results, it was found that only anxiety level was related to sleep pattern (r = .519, p &lt; .05). Meanwhile, age and education level have no relationship with sleep patterns. Conclusion: The anxiety level of cervical cancer patients in facing external radiotherapy treatment can affect their sleep patterns, so understanding is needed by a health worker to reduce the patient's anxiety.

Designing Patient-Centered Health Education Materials for Radiation Dermatitis in Breast Cancer Patients: A Pilot Study and Single-Center Clinical Trial.

For breast cancer patients receiving radiotherapy (RT), radiation dermatitis is the most commonly experienced discomfort. However, patients usually do not participate in the design of health education materials regarding radiation dermatitis. We designed a pilot study to investigate the unmet need of breast cancer patients who would be receiving RT at our department and created a patient-centered educational video. We initiated a single-arm clinical trial to evaluate the effectiveness of the video in improving patient and their family's knowledge of radiation dermatitis, alleviating their anxiety, and helping patients improve self-care skills during RT course. The pilot study was executed in a radiation oncology department of a tertiary medical center in Taiwan. We designed a questionnaire to explore new breast cancer patients' idea of a comprehensive pre-RT health education. Enrolled patients would fill out an electronic questionnaire during their first visit at our outpatient clinic. They were asked to select at most two of the following items they considered most important for pre-RT health education: (1) The mechanism behind RT; (2) Self-care skills for irradiated skin; (3) Activities to be avoided during RT course; (4) The toxicity grading of radiation dermatitis. Given the above information, we created a 4-minute video set in a clinical scenario of a patient receiving pre-RT health education from a nurse. A single-arm clinical trial (IRB approval number: CMUH111-REC2-121) is currently recruiting. The video was launched on YouTube (Link: https://youtu.be/O1uTXpS_ed0) to give patients easy access to the video. Enrolled patients would complete Skindex-16 survey (translated into Chinese) at 3 timepoints: during their first visit at our clinic, in the middle of RT course, and at the first post-RT follow-up visit. Cronbach's alpha test was applied to determine the internal consistency of the questionnaires. The pilot study included 19 patients with an average age of 46.6 (range: 34 to 69) years old. All patients' primary language was Chinese Mandarin. Most patients (84%) received at least secondary education. We found by surprise that RTOG skin toxicity grading was considered very important for most patients (79%), while less than half (42%) found the mechanism behind RT important. The internal validity of the Chinese version of Skindex-16 was good (Cronbach's alpha score = 0.87). For the recruiting trial, we have enrolled 10 patients and planned to close the trial upon enrolling 50 participants. The study result should be available before August 2023. We suggest to actively involve patients in designing health education materials for patient-centered care. Toxicity grading of radiation dermatitis should be included in pre-RT health education for breast cancer patients. Whether the educational video helps reduce patients' anxiety and the incidence of severe radiation dermatitis will soon be answered by our ongoing clinical trial.

Analysis of Artificial Intelligence-Based Automated Phenotyping of Coronary Artery Disease Diagnoses for Patients who Received Radiotherapy for Thoracic Malignancies.

Coronary artery disease (CAD) is a critical risk factor and toxicity endpoint in thoracic radiation oncology. The recent advent of artificial intelligence (AI) algorithms - specifically natural language processing (NLP) - allows for automated extraction of this data from electronic health records (EHR) more efficiently and at scale. We report on the application and performance characteristics of an EHR-based automated phenotyping tool to a cohort of lung cancer patients receiving radiation therapy (RT). We applied to this radiation oncology use-case an AI-based disease phenotyping tool developed by other researchers for phenotyping CAD from the EHR. The CAD model was trained on 191,187 patients with at least one ICD code and validated with 158 gold-standard patients (Sensitivity: 73%, Specificity: 93%, PPV: 90%). NLP disease definitions were determined by UMLS and were employed with ICD codes through PheNorm classification method to create the phenotype algorithm (Yue et al., J Am Med Inform Assoc. 2018 Jan 1; 25(1):54-60). We applied the CAD phenotyping tool to two independent cohorts of RT treated lung cancer patients: 1) an annotated set of 677 patients who received RT from 1998 to 2014 and were studied in prior cardiac toxicity research; 2) an independent set of 209 patients who received RT from 1998 to 2018 and were annotated separately. Only 7.7% of the AI training population had a CAD diagnosis code, compared to 32.5% and 65.0% in the 677 patient and 209 patient cohorts, respectively. Validation of the AI predicted CAD is shown in the table below. Performance on the 209 patient cohort best matched the AI training set. The 677-patient cohort differed from the 209-patient cohort in that its CAD definition included patients with radiographic coronary artery calcifications, which accounted for the difference in cohort sensitivities, F-scores, and NPVs. The AI calculated CAD was somewhat accurate in detecting whether a patient had CAD and was very accurate in confirming no CAD. The differences in sensitivity and NPV reflect differences in defining CAD, but this study demonstrates the potential for automated AI-phenotyping to detect pre-treatment risk factors and cardiac toxicity events from the EHR.

The Role of Pre-bone Marrow Transplantation Pulmonary Function Test in Predicting Post-transplant Noninfectious Pulmonary Complications

Background: Pulmonary function test (PFT) is used as a tool for pre-transplant risk assessment and as a predictor of post-transplant outcomes. As there are currently few studies that discuss the role of PFT in bone marrow transplantation (BMT) patients in Saudi settings, and as the number of transplant patients with benign and malignant conditions continues to increase, this study was conducted with the aim of assessing the local practice. Methods: This retrospective cohort study included all adult patients who underwent BMT at Princess Noorah Oncology Center, King Abdulaziz Medical City, Jeddah, between 2014 and 2020. The association between established patient-related risk factors and the incidence of pulmonary complications among autologous and allogeneic groups was assessed. Results: A total of 186 patients were included (autologous = 143; allogenic = 43), of which 115 (61.8%) were male. At the pre-BMT phase, about 30% of the patients had comorbidities and 51% had received two rounds of salvage chemotherapy, while 16.1% had received radiation therapy. In the autologous group, the only PFT parameter that was a significant predictor of post-BMT pulmonary complications was forced vital capacity &lt;80% (P = 0.012), while in the allogenic group, no parameter was significantly associated with pulmonary complications. The patient-related factors that were associated with respiratory distress in the autologous group were lung involvement (P = 0.03) and pre-transplant radiation (P = 0.044). Conclusion: The findings of this study indicated that forced vital capacity &lt;80% was a significant factor in predicting non-infectious complications in the autologous group. Furthermore, lung involvement and pre-transplant radiation were the patient-related factors associated with pulmonary complications.

Coping Strategies among Filipino Cancer Patients Undergoing Radiation Therapy in Two Tertiary Care Hospitals in the Philippines: An Analytical Cross-Sectional Study.

The process of coping is central in the lives and experiences of cancer patients. Foreign literature on coping strategies among cancer patients is largely qualitative in nature, in the form of thematic, grounded theory, and phenomenological analyses. Of the quantitative research that has been done, many have found varying degrees of association between certain coping strategies and improved quality of life and decreased emotional distress. However, knowledge on how coping varies and is associated with the patient's demographics, disease characteristics, among other factors remains in its infancy. This is especially true in the Philippines. A total of 210 Filipino patients more than 18 years of age, with histologically confirmed diagnosis of cancer, receiving radiation therapy at St. Luke's Medical Center-Quezon City or St. Luke's Medical Center-Bonifacio Global City from April 2022 to December 2022, were made to answer the Filipino Coping Strategies Scale (FCSS). The FCSS is a self-administered, 37-item, 4-point scale that measures the degree to which the respondent uses particular coping strategies categorized into one of nine domains: cognitive reappraisal, social support, problem-solving, religiosity, tolerance, emotional release, overactivity, relaxation and recreation, and substance use. Religiosity is the primary coping strategy in this patient population, with a composite score of 3.9214 out of 4 (SD = 0.1688). The second most utilized coping strategy is problem-solving (composite score = 3.6310; SD = 0.3162). The third most common coping strategy is cognitive reappraisal (composite score = 3.5524; SD = 0.4062). This is closely followed by relaxation and recreation (composite score = 3.5343; SD = 0.3734). The fifth most utilized coping strategy is social support (composite score = 3.3140; SD = 0.5790). Calculation of independent samples t-test revealed no statistically significant difference between the coping strategies in terms of hospital (i.e., St. Luke's Quezon City or St. Luke's Bonifacio Global City), sex, metastatic status, and intent of radiotherapy. Calculation of analysis of variance (ANOVA) likewise revealed no statistically significant difference in terms of age, marital status, religion, educational attainment, estimated monthly income, primary cancer diagnosis, days elapsed since primary cancer diagnosis, Wong-Baker Faces (WBF) pain rating, and Eastern Cooperative Oncology Group (ECOG) performance status. The most commonly utilized coping strategies in our patient cohort are religiosity, problem-solving, cognitive reappraisal, relaxation and recreation, and social support, regardless of demographic and disease-related characteristics. To the proponents' knowledge, our research is the first to study the coping strategies of Filipino cancer patients in a quantitative manner. Doubtless, further research is needed to shed light on this crucial but barely yet untouched aspect of cancer care.

INDIVIDUAL ARTICLE: NECOM 3: A Practical Algorithm for the Management of Radiation Therapy-Related Acute Radiation Dermatitis.

In the Nordic European countries in 2020, cancer diagnoses accounted for 175,925 patients. About 50% of cancer patients receive radiation therapy (RT), which may lead to radiation dermatitis (RD). Notably, patients with breast, head, neck, and anal cancers may be prone to developing RD. However, few algorithms exist for the prevention and treatment of RD. The Nordic European Cutaneous Oncodermatology Management (NECOM) project aims to improve cancer patient outcomes by offering tools to prevent and treat cancer therapy-related cutaneous adverse events (cAEs). The first 2 NECOM papers presented various cAEs and skincare regimens involving hygiene, moisturization, sun protection, and camouflage products for preventing and managing cAEs. The NECOM 3 practical algorithm for preventing and managing acute RD (ARD) is intended to promote healthy skin and reduce RT-related ARD, improving cancer patient outcomes.&nbsp; Results: The NECOM advisors discussed the results of a systematic literature review and obtained consensus on the evidence and opinion-based practical algorithm for ARD to support all stakeholders in the Nordic European healthcare setting. The algorithm starts with skin-preserving therapy, followed by skin condition assessment and patient-specific interventions based on the grade of RD present.&nbsp; Conclusion: ARD may lead to symptoms of pruritus and pain, decreased QoL and morbidity, and treatment interruptions. Patient education on the prevention of RD and treatment recommendations given in the NECOM 3 algorithm may help prevent and manage RD and improve the overall care of patients receiving RT. J Drugs Dermatol. 2023;22:11(Suppl 2):s3-s10.

Development and Validation of MRI Imaging Biomarkers for Prostate Cancer Using Deep Learning.

Given the increasing number of treatment options for patients with localized prostate cancer (PCa), there is a need for biomarkers to aid in risk stratification. Specifically, novel biomarkers can aid in the identification of high-risk phenotypes among similar patients in traditional NCCN risk groupings. One promising area for development is using pre-treatment prostate MRI to identify imaging biomarkers to identify prostate cancer patients at highest risk for recurrence. We hypothesized that deep learning could be leveraged to identify imaging biomarkers of aggressive PCa from pre-treatment prostate MRIs. Our study included 1,020 patients treated at our institution between 2010-2022. Given pathologic extraprostatic extension (EPE) and seminal vesicle invasion (SVI) are associated with higher risk of treatment failure, we hypothesized that deep learning models which identified radiographic EPE and SVI would provide non-invasive imaging biomarkers associated with PCa prognosis. We trained two separate deep learning models using convolutional neural networks to predict SVI and EPE respectively. The model inputs were T2W prostate MRIs (n = 894) and models consisted of 8 convolutional layers. Dropout, L2 regularization, and data augmentation were used to improve model generalizability and reduce overfitting. Discriminatory ability of each model was measured using AUC on a blinded external test set of 221 patients. To assess the clinical utility of our imaging biomarkers, log-rank tests were used to evaluate biochemical free survival (BFS) for patients classified as high risk to patients classified as low risk. Biochemical failure was defined as post-treatment PSA >0.1 for patients who underwent radical prostatectomy (RP) or PSA >2ng/ml above nadir for patients receiving radiation therapy. Within our cohort of 1,020 patients the median age was 66 with a median follow up of 4 years. 49.3% (n = 503) underwent RP and 50.7% (n = 517) received EBRT. 4% (n = 41) were low risk, 62.4% (n = 636) were intermediate risk, and 33% (n = 337) were high risk based on NCCN criteria. Deep learning models showed good discriminatory ability for both EPE (AUC 0.66) and SVI (AUC 0.74). Both imaging biomarkers showed prognostic ability to identify high risk prostate phenotypes. Patients deemed high risk based on EPE classifier had worse BFS (median 5 vs 9 years, p<.001). Similarly, patients classified as high risk based on SVI also showed worse BFS (median 5 vs 9 years, p = 0.024). Among intermediate risk patients, EPE biomarker showed an ability to identify high risk phenotypes (median 6 vs 9 years, p = 0.024). Deep learning classifiers of prostate MRIs demonstrated the ability to stratify high-risk prostate cancer phenotypes beyond traditional risk paradigms. Imaging biomarkers represent a non-invasive method to help aid in the personalization of treatment for patients with localized prostate cancer and identify patients who potentially require treatment escalation.

A Systematic Review and Network Meta-Analysis Assessing the Impact of Adding First Generation Non-Steroidal Anti-Androgens (NSAA) to LHRH Agonists (LHRHa) in Men Receiving Radiotherapy for Localized Prostate Cancer.

Randomized clinical trials consistently demonstrate that the addition of androgen deprivation therapy (ADT) to prostate radiation therapy improves overall survival (OS). However, there is substantial heterogeneity regarding the type of ADT: LHRHa alone, first generation NSAA alone (e.g., bicalutamide) or combination androgen blockade (CAB) with NSAA and LHRHa. There are no published randomized trials in localized disease that specifically compare the efficacy of NSAA to LHRHa, nor the utility of CAB over monotherapy ADT. We herein performed a systematic review and network meta-analysis to assess the impact of NSAA in relation to LHRHa in men receiving radiotherapy for localized prostate cancer. We performed a systematic literature search in PubMed to identify clinical trials of patients with localized prostate cancer for which ADT duration was the primary randomization variable. Both definitive and salvage radiation trials were included. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated from data extracted from published survival curves. A network meta-analysis was performed to compare OS by ADT regimens. We defined NSAA toxicity as early discontinuation of any ADT agent due to side effects given the inconsistent reporting of specific related toxicity. A meta-regression was performed to assess association with NSAA toxicity, adjusted for study year, patient age, T stage, Gleason score and total ADT duration. NSAA duration was assessed as a continuous variable. Of the 11 trials (8,169 patients) with OS data, the median duration of any ADT was 3 months (range 0-36 months) and the median duration of NSAA specifically was 3.5 months (range 0-24 months). There was no significant difference in OS between those treated with LHRHa (n = 369) vs. CAB (n = 4,792; HR 1.10, 95% CI 0.78-1.55). Among those receiving CAB, increased NSAA duration did not improve OS (versus 0 months; 1-6 months HR 1.41, 95% CI 0.94-2.13; 7-12 months HR 1.43, 95% CI 0.87-2.34) when controlling for total ADT duration. Of the 19 trials (15,067 patients) with toxicity data, patients on NSAA (n = 503) appeared more likely to discontinue treatment early compared to those receiving LHRHa (n = 902), though this was not statistically significant (odds ratio [OR] 4.20, 95% CI 0.16-109.19). A longer duration of NSAA did not adversely affect ADT compliance. Patients were more likely to discontinue ADT prematurely, regardless of type, if the planned duration was longer (OR 1.08, 95% CI 1.07-1.09). We did not detect an overall survival benefit to adding NSAA to LHRHa, and NSAA appeared less well tolerated than LHRHa in men receiving radiation therapy for localized prostate cancer. These data suggest that providers should consider LHRHa without the addition of a NSAA as optimal when clinically appropriate.

The efficacy of the TRK inhibitor entrectinib in patients with extracranial &lt;i&gt;NTRK&lt;/i&gt; fusion-positive tumors

Somatic translocations involving the NTRK genes occur in 0.34–2.2% of all malignant neoplasms in children. TRK inhibitors whose efficacy has been demonstrated in prospective clinical studies expand treatment options for patients with solid tumors harboring NTRK gene rearrangements. The aim of our study was to summarize the first Russian experience with the use of the TRK inhibitor entrectinib in patients with extracranial NTRK fusion-positive solid tumors included in the compassionate use program. This study was approved by the Independent Ethics Committee and the Academic Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. The study included 8 patients who had been treated at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology and the N.N. Blokhin National Medical Research Center of Oncology. The main criteria for inclusion in the compassionate use program were a confirmed rearrangement of either NTRK1/2/3 genes in a solid tumor in patients with unresectable disease for whom no effective standard systemic therapy was available, progressive or recurrent disease during therapy prescribed according to the established diagnosis, risk group and risk stratification criteria, and the infeasibility of non-mutilating radical surgery. The median age at diagnosis was 4.3 months (range 1.2–83.6). The male to female ratio was 1:1. The primary site distribution was as follows: head and neck (n = 6; 75%), chest wall (n = 1; 12.5%), pelvis (n = 1; 12.5%). None of the patients had regional lymph node involvement or distant metastases at diagnosis. The distribution by histology (according to histopathology reports) was as follows: infantile fibrosarcoma (n = 4; 50%), undifferentiated round cell sarcoma, low-grade (n = 1; 12.5%), undifferentiated spindle cell sarcoma, high-grade (n = 1; 12.5%), NTRK-rearranged spindle cell sarcoma, low-grade (n = 1; 12.5%), spindle cell tumor associated with an NTRK rearrangement (n = 1; 12.5%). Immunohistochemistry (IHC) with a pan-Trk monoclonal antibody was performed in 7/8 (87.5%) patients. Pan-Trk IHC was positive in 4/7 (57%) patients. Rearrangements in the NTRK1 and NTRK3 genes were confirmed in all the patients. The final methods used for the detection of fusion transcripts were as follows: reverse transcription polymerase chain reaction (n = 4; 50%) and RNA-based next-generation sequencing (n = 4; 50%). NTRK1 and NTRK3 gene translocations were detected in 3/8 (37.5%) and 5/8 (62.5%) patients, respectively. The following fusion transcripts were identified: ETV6::NTRK3 (n = 4), DIP2C::NTRK3 (n = 1), TPR::NTRK1 (n = 1), TPM3::NTRK1 (n = 1), MYH10::NTRK1 (n = 1). One (12.5%) patient received entrectinib as first-line therapy, other patients (7/8, 87.5%) received entrectinib as secondor subsequent-line therapy. Three (37.5%) patients had undergone surgery before treatment with entrectinib: 2 had R2 resection, 1 had R0/R1 resection (resection margins were not evaluated). None of the patients received radiation therapy. The median duration of entrectinib therapy at the time of analysis was 11.8 months (range 2.3–20.1). Delayed surgery was performed in 2/8 patients; according to the histopathology reports, they achieved grade IV pathomorphosis. Three patients experienced adverse events during treatment with entrectinib. The median time to adverse events was 0.23 months (range 0.2–7.96). Three patients required temporary interruption in treatment to relieve symptoms, a subsequent dose reduction by one dose level was necessary when resuming therapy in two patients. The median follow-up since diagnosis was 19.5 months (range 14.9–75.0). All the patients included in our analysis were alive, three of them had no radiologic evidence of disease. Fifty percent of the patients completed targeted therapy, another 50% of the patients continued treatment with entrectinib. Complete and very good partial response was achieved in 3/8 and 2/8 patients, respectively. Partial response, minor partial response and stable disease were observed in one patient each. These results indicate high efficacy and safety of entrectinib in pediatric patients with extracranial NTRK fusion-positive solid tumors. Further studies are needed to determine the therapeutic potential of TRK inhibitors in the treatment of different solid malignant neoplasms in children and to assess long-term treatment results.

Limitations in the Application of Clinicopathologic Factors Alone in Predicting Radiation Benefit for Women with Low-Risk DCIS after Breast Conserving Surgery: The Impact of a 7-Gene Biosignature Based on 10-Year Ipsilateral Breast Recurrence (IBR) Rates

Most women diagnosed with ductal carcinoma in situ (DCIS) receive radiotherapy (RT) after breast conserving surgery (BCS); however, clinical trials show that over 70% of women with BCS alone will not have a recurrence and therefore not benefit from RT. Traditionally, clinicopathologic (CP) factors have been used to select for whom to de-escalate treatment, but prospective trials have failed to identify a low risk CP group that did not benefit from RT with respect to local control. This study assessed the re-classification of patients with low-risk CP into Risk groups defined by the 7-gene biosignature and compared to 10-yr IBR rates. Women (n = 926) from four international DCIS cohorts treated with BCS had formalin-fixed paraffin embedded tissue samples analyzed at a CLIA lab (Laguna Hills, CA). CP low-risk patients were identified using a) RTOG-9804-like criteria [Nuclear Grade 1 or 2 & Size ≤2.5 cm & non-Palpable & Screen Detected & margin negative (no-ink on tumor)] and b) MSKCC-like criteria [low-risk score<220, determined using nomogram weighted factors (excluding: number of re-excisions and RT treatment), and using no-ink-on-tumor instead of close margin]. The 7-gene DCIS biosignature combined biomarkers with CP factors (age, size, palpability, and margin status) using an algorithm reporting a Decision Score (DS) and Residual Risk subtype (RRt). Women with low-risk CP were classified into biosignature Low Risk (DS≤2.8, no RRt) or High Risk (DS>2.8 +/- RRt) groups. 10yr in-breast event (IBR) rates with and without RT were assessed by Kaplan-Meier rates and Cox proportional hazard analyses. Overall, 37% of all women were classified into the biosignature Low Risk group, while 51% and 34% were classified into CP low-risk groups (RTOG-9804-like, MSKCC-like, respectively). The biosignature Low Risk group (n = 338) had a 10-yr IBR risk of 5.6% after BCS and no significant RT benefit (absolute RT benefit = 0.8%, p = 0.70), 99% negative predictive value (NPV) for RT benefit. CP low-risk groups had 10-yr IBR rates of 12% and 8% after BCS without RT with absolute 6% (p = 0.04) and 4% (p = 0.1) IBR rate reductions with RT. The biosignature reclassified 51% and 63% of CP low-risk patients into the biosignature High Risk group. Importantly, these patients had higher IBR rates without RT (20% and 12%) and significant 13% (p = 0.005) and 8% (p = 0.01) absolute IBR rate reductions from RT. CP low-risk patients with concordant biosignature Low Risk demonstrated no significant RT benefit. The 7-gene predictive biosignature more reliably identified patients with low 10-yr IBR rates and no significant RT benefit than the traditional CP low-risk criteria (RTOG-9804-like, MSKCC-like). Importantly, those CP low-risk patients who were re-classified as biosignature High Risk had increased 10-year IBR rates and significant RT benefit.

Risk of Subsequent Neoplasms in Childhood Cancer Survivors After Radiation Therapy: A PENTEC Comprehensive Review

A Pediatric Normal Tissue Effects in the Clinic (PENTEC) analysis of published investigations of central nervous system (CNS) subsequent neoplasms (SNs), subsequent sarcomas, and subsequent lung cancers in childhood cancer survivors who received radiation therapy (RT) was performed to estimate the effect of RT dose on the risk of SNs and the modification of this risk by host and treatment factors. A systematic literature review was performed to identify data published from 1975 to 2022 on SNs after prior RT in childhood cancer survivors. After abstract review, usable quantitative and qualitative data were extracted from 83 studies for CNS SNs, 118 for subsequent sarcomas, and 10 for lung SNs with 4 additional studies (3 for CNS SNs and 1 for lung SNs) later added. The incidences of SNs, RT dose, age, sex, primary cancer diagnosis, chemotherapy exposure, and latent time from primary diagnosis to SNs were extracted to assess the factors influencing risk for SNs. The excess relative ratio (ERR) for developing SNs as a function of dose was analyzed using inverse-variance weighted linear regression, and the ERR/Gy was estimated. Excess absolute risks were also calculated. The ERR/Gy for subsequent meningiomas was estimated at 0.44 (95% CI, 0.19-0.68); for malignant CNS neoplasms, 0.15 (95% CI, 0.11-0.18); for sarcomas, 0.045 (95% CI, 0.023-0.067); and for lung cancer, 0.068 (95% CI, 0.03-0.11). Younger age at time of primary diagnosis was associated with higher risk of subsequent meningioma and sarcoma, whereas no significant effect was observed for age at exposure for risk of malignant CNS neoplasm, and insufficient data were available regarding age for lung cancer. Females had a higher risk of subsequent meningioma (odds ratio, 1.46; 95% CI, 1.22-1.76; P < .0001) relative to males, whereas no statistically significant sex difference was seen in risk of malignant CNS neoplasms, sarcoma SNs, or lung SNs. There was an association between chemotherapy receipt (specifically alkylating agents and anthracyclines) and subsequent sarcoma risk, whereas there was no clear association between specific chemotherapeutic agents and risk of CNS SNs and lung SNs. This PENTEC systematic review shows a significant radiation dose-response relationship for CNS SNs, sarcomas, and lung SNs. Given the linear dose response, improved conformality around the target volume that limits the high dose volume might be a promising strategy for reducing the risk of SNs after RT. Other host- and treatment-related factors such as age and chemotherapy play a significant contributory role in the development of SNs and should be considered when estimating the risk of SNs after RT among childhood cancer survivors.

Skin Microbiome Composition is Associated with Radiation Dermatitis in Breast Cancer Patients Undergoing Radiation after Reconstructive Surgery: A Prospective, Longitudinal Study

Approximately 95% of breast cancer (BC) patients receiving radiotherapy (RT) develop varying degrees of radiation dermatitis (RD), which can greatly affect the patient's quality of life and aesthetics. Severe acute RD can lead to interruption or delay of RT. Currently, there is no consensus on the prevention and management of RD. The skin microbiota (SM), which are mainly composed of bacteria and fungi, are essential for skin homeostasis and microbial dysbiosis is correlated with the onset and progression of many common skin diseases. However, to date, research on the role of the SM in RD remains scarce. This prospective, longitudinal study aims to analyze the association of SM with RD. We collected 200 SM samples both before and after RT from the region in the irradiated chest wall of 100 BC patients receiving RT after reconstructive surgery and samples from the corresponding region in the contralateral breast for bacterial 16S and fungal ITS (internal transcribed spacer) rRNA sequencing. Acute RD was graded according to the Toxicity Criteria of the Radiation Therapy Oncology Group (RTOG). Patients were divided into no or mild dermatitis (N/MD, RTOG grade 0 or 1) and severe dermatitis (SD, RTOG grade 2 and above). The compositional differences across groups were compared using STAMP and high-dimensional class comparisons by linear discriminant analysis of effect size (LEfSe). Differences in metabolic function between groups were predicted by the Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) method. Significant differences were observed in the diversity and composition of the SM between N/MD and SD both before and after RT. Analysis of bacterial 16S sequencing (n = 89, 63 N/MD, 26 SD) showed significantly higher relative abundance of particular taxa such as Ralstonia, Truepera, Methyloversatilis genera and lower abundance of particular taxa including Staphylococcus, Corynebacterium genera in N/MD patients. Besides, analysis of fungal ITS sequencing (n = 71, 53 N/MD, 18 SD) showed significantly higher relative abundance of particular taxa such as Hypocreaceae family and lower abundance of particular taxa such as Sporidiobolus genus in N/MD patients. Pathways including fatty acid synthesis were predicted to be enriched in N/MD patients. The SM and pathway markers were identified in this study to be associated with the severity of acute RD in BC patients undergoing RT after reconstructive surgery. More patient data is needed to verify the current findings and the results of metagenomic, metatranscriptomic, and metabolomic analyses will further mine key biomarkers at the compositional and functional level.