The Role of Local Therapy for Oligo-Progressive Disease in Oncogene-Addicted Non-Small-Cell Lung Cancer.

Purpose: We first described the role of local radiation therapy (LT) for oligoprogressive disease (OPD) on targeted therapy in 2012. Here, we present an updated and larger data set and extend the analysis beyond EGFR and ALK. Methods: A retrospective review of patients with metastatic NSCLC harboring EGFR/BRAF V600E mutations, or ALK/ROS1/RET rearrangements, who had OPD on respective tyrosine-kinase inhibitor (TKI) and treated with LT was performed. OPD was defined as disease progression on therapy in ≤5 sites. PFS1 (progression-free survival 1) was defined as time from initiation of TKI-containing regimen to the first course of LT for OPD. Subsequent PFS times (eg, PFS2, PFS3) were defined as time from prior LT to subsequent LT, switch of systemic therapy, death, or loss to follow-up, whichever occurred first. Extended-PFS was defined as time from the first day of the first LT course to the day of change in systemic therapy, death, or loss to follow-up, whichever came first. Results: Eighty-nine patients were identified. In 75.4% of the LT courses, a single lesion was treated. Median PFS1 was 10.2 months (95% CI, 8.7-13.1) and median Extended-PFS was 6.7 months (95% CI, 4.9-8.3). Extended-PFS was similar across different oncogenic drivers; 51.4% of patients who underwent LT to a single site had only 1 site on next disease progression. Conclusions: LT is effective in prolonging treatment duration on TKI in oncogene-addicted NSCLC across multiple oncogenes.

Pilot Curriculum for Continued Professional Development of Radiation Oncology Nurses.

Purpose: Limited structured educational programs are available for the continued professional development of radiation oncology nurses. In this study, we evaluated a pilot curriculum focusing on clinical workflow and toxicity management for radiation oncology nurses at a single university-affiliated medical center network. Methods and Materials: Based on a previous multi-institutional needs assessment, a targeted curriculum on clinical workflow and toxicity management was developed, including didactic lectures, written disease-specific toxicity management guidelines, and standardized medication/laboratory order preference lists in the electronic health record. An anonymized survey was circulated to all participants pre- and postcurriculum. The survey was composed of Likert-type subjective questions and 11 objective knowledge-based questions (KBQs). Paired Likert-type data were analyzed using Wilcoxon signed ranks test. Objective question data were compared with the McNamar's mid P test. Results: Thirteen nurses participated in the pilot curriculum and 100% completed pre- and post curriculum surveys. After the didactics, nurses reported a significant increase in their understanding of the responsibilities of a nurse and overall process of care and their ability to explain computed tomography simulation, as well as their ability to assess, manage, and grade radiation-related toxicities (P < .01). There was significant improvement in the percent of correct answers on objective KBQs from a baseline of 52% to 80% after the curriculum (P < .01). Qualitatively, 70% (9/13) of nurses rated the curriculum as "extremely useful" and 30% (4/13) as "quite useful." Conclusions: Our pilot curriculum using a combination of in-person formal didactics, toxicity management guidelines, and electronic health record based order preference lists was well-received and showed promising results on KBQ assessment. This work may be used to guide the development of larger curricula for nurse onboarding and continuing education in a multicenter setting.

The Kelowna template for combined intracavitary and interstitial brachytherapy for gynecologic malignancies: Design, application, treatment planning, dosimetric and treatment outcomes.

PURPOSE: We report the feasibility, experience, and early outcomes of the combined intracavitary and interstitial dedicated applicator using the Kelowna GYN template (Varian, Palo Alto, CA). METHODS AND MATERIALS: The Kelowna GYN template is CT compatible and used for the treatment of gynecologic cancers. In cases with patients that have an intact uterus, a modified applicator system using the Kelowna GYN template and a 3D printed adapter piece allows for compatibility with an intrautaerine tandem. RESULTS: We reviewed the treatment course of 23 patients comprising of 86 fractions of HDR treatment. Median D90 for cervical tumors (n = 7) was 82.4 Gy (range 77.7-92.6); for postoperative cervical tumors (n = 2) was 73.9 Gy (range 72.0-5.8); for vaginal tumors (n = 4) was 85.8 Gy (range 79.8-88.1); for recurrent endometrial (n = 10) was 86.9 Gy (range 74.8-103.2). Median EQD2 D2cc for bladder was 72.4 Gy (range 47.7-99.4), for rectum was 61.2 Gy (range 52.4-80.6), and for sigmoid colon of 50.5 Gy (44.3-66.9). At a median follow-up of 12 months, 2 patients had a local recurrence. Two patients had distant recurrence: one with carcinomatosis at 6 months, and one with pulmonary metastases at 3 months. No patients had late grade three toxicities. CONCLUSIONS: Our single institutional experience supports the use of the Kelowna template as a robust system as a combined IC-IS applicator resulting in versatile and reproducible implants for a variety of gynecologic malignancies.

Gynecologic interstitial brachytherapy curriculum using a low-cost phantom with ultrasound workshop and a treatment planning workshop is effective.

PURPOSE/OBJECTIVE(S): Standardized simulation training geared towards interstitial brachytherapy (IS BT) for gynecologic malignancies is lacking in radiation oncology resident education. We developed and implemented a curriculum for IS BT training with (1) lecture on equipment, workflow, and guidelines, (2) hands-on ultrasound-guided IS BT workshop, and (3) treatment planning workshop. METHODS AND MATERIAL: The cost in materials of each phantom was approximately $66. After a lecture, two alternating workshops were performed. The first session consisted of a hands-on ultrasound-guided IS BT workshop with one resident imaging the phantom with a transabdominal ultrasound probe and the other resident implanting the phantom with needles. A second session consisted of a hands-on treatment planning workshop using BrachyVision and an l-Q spreadsheet with the following objectives: coverage goal, meeting D2cc constraints, and minimizing V200. The primary outcome was improvement in knowledge assessed with Likert-style questions and objective knowledge-based questions (KBQs). RESULTS: Four of the seven medical residents that participated in this curriculum had prior IS BT experience. Residents reported significantly improved knowledge regarding gynecologic IS BT equipment and procedure, evaluating gynecologic anatomy using ultrasound, CT simulation, contouring, and plan review (overall median pre-session subjective score 2 (1) -(3) versus post-session score 4 (3) -(4, p < 0.01). Residents demonstrated improvement in answering KBQs correctly from 44% correct at baseline to 88% after completion of the curriculum (p < 0.01). All residents "Agree" and "Strongly Agree" the session was an effective learning experience. CONCLUSIONS: Residents participating in phantom training with an ultrasound curriculum and a treatment planning session is effective for improving knowledge and skills in IS BT for radiation oncology residents.

Improving the Pediatric Patient Experience During Radiation Therapy-A Children's Oncology Group Study.

PURPOSE: Treatment with radiation therapy (RT) can cause anxiety and distress for pediatric patients and their families. Radiation oncology teams have developed strategies to reduce the negative psychological impact. This survey study aimed to characterize these methods. METHODS AND MATERIALS: A 37-item questionnaire was sent to all radiation oncology members of the Children's Oncology Group to explore strategies to improve the pediatric patient experience. The Wilcoxon rank-sum test was used to assess factors associated with use of anesthesia for older children. RESULTS: Surveys were completed by 106 individuals from 84/210 institutions (40%). Respondents included 89 radiation oncologists and 17 supportive staff. Sixty-one percent of centers treated ≤50 children per year. Respondents described heterogenous interventions. The median age at which most children no longer required anesthesia was 6 years (range: ≤3 years to ≥8 years). Routine anesthesia use at an older age was associated with physicians' lack of awareness of these strategies (P = .04) and <10 years of pediatric radiation oncology experience (P = .04). Fifty-two percent of respondents reported anesthesia use added >45 minutes in the radiation oncology department daily. Twenty-six percent of respondents planned to implement new strategies, with 65% focusing on video-based distraction therapy and/or augmented reality/virtual reality. CONCLUSIONS: Many strategies are used to improve children's experience during RT. Lack of awareness of these interventions is a barrier to their implementation and is associated with increased anesthesia use. This study aims to disseminate these methods with the goal of raising awareness, facilitating implementation, and, ultimately, improving the experience of pediatric cancer patients and their caregivers.

Impact of neoadjuvant chemotherapy and stereotactic body radiation therapy (SBRT) on R0 resection rate for borderline resectable and locally advanced pancreatic cancer.

BACKGROUND: The role of neoadjuvant stereotactic body radiation therapy (SBRT) in patients with borderline resectable pancreas cancer (BRPC) and locally advanced pancreas cancer (LAPC) remains controversial. METHODS: We retrospectively evaluated BRPC and LAPC patients treated at our institution who underwent 2-3 months of chemotherapy followed by SBRT to a dose of 30-33 Gy. Overall survival (OS) and recurrence-free survival (RFS) were estimated and compared by Kaplan-Meier and log-rank methods. RESULTS: We identified 103 (85 BRPC and 18 LAPC) patients treated per our neoadjuvant paradigm between 2011 and 2018, with resectability based on NCCN definitions. Median follow up was 25 months. Of patients completing neoadjuvant therapy, 73 (71%) underwent definitive resection. Seventy-one (97%) patients with definitively resected tumors had R0 resection and 5 (7%) had a complete pathologic response CR to neoadjuvant therapy. The median overall survival (OS) of the cohort was 24 months. Those with a complete or marked pathologic response had significantly better OS than those with a moderate response (41 vs 24 months, p < 0.02) and patients unable to undergo definitive surgery (17 months, p < 0.0003). Six resected patients experienced grade ≥3 surgical complications. CONCLUSIONS: Neoadjuvant chemotherapy and SBRT are associated with promising pathologic response rates and R0 resection rates, with acceptable perioperative morbidity.

TMEM16A/ANO1 suppression improves response to antibody-mediated targeted therapy of EGFR and HER2/ERBB2.

TMEM16A, a Ca2+ -activated Cl- channel, contributes to tumor growth in breast cancer and head and neck squamous cell carcinoma (HNSCC). Here, we investigated whether TMEM16A influences the response to EGFR/HER family-targeting biological therapies. Inhibition of TMEM16A Cl- channel activity in breast cancer cells with HER2 amplification induced a loss of viability. Cells resistant to trastuzumab, a monoclonal antibody targeting HER2, showed an increase in TMEM16A expression and heightened sensitivity to Cl- channel inhibition. Treatment of HNSCC cells with cetuximab, a monoclonal antibody targeting EGFR, and simultaneous TMEM16A suppression led to a pronounced loss of viability. Biochemical analyses of cells subjected to TMEM16A inhibitors or expressing chloride-deficient forms of TMEM16A provide further evidence that TMEM16A channel function may play a role in regulating EGFR/HER2 signaling. These data demonstrate that TMEM16A regulates EGFR and HER2 in growth and survival pathways. Furthermore, in the absence of TMEM16A cotargeting, tumor cells may acquire resistance to EGFR/HER inhibitors. Finally, targeting TMEM16A improves response to biological therapies targeting EGFR/HER family members.

Salvage stereotactic radiosurgery for recurrent glioblastoma multiforme with prior radiation therapy.

BACKGROUND: Glioblastoma multiforme (GBM) carries a poor prognosis with high recurrence rates. Salvage stereotactic radiosurgery (SRS) may be an effective treatment option. METHODS: We retrospectively reviewed 34 patients (41 lesions) treated with salvage SRS for recurrent GBM between 2004 and 2012. Initial surgical treatments were gross total resection (58%), subtotal resection (STR) (24%), and biopsy (18%). All patients were treated with prior radiation therapy. Recurrent disease was treated with salvage SRS with a median dose and fractions of 23.4 Gy (range, 12-30) and 3 (range, 1-3), respectively. Cox proportional hazards regression was conducted to establish predictive factors (P ≤ 0.05) Results: Median follow-up from salvage SRS was 10.8 months (interquartile range [IQR], 7.0-15.6). The median time from initial radiation therapy to salvage SRS was 13.7 months (IQR, 2.9-25.0). The 6- and 12-month overall survival from salvage SRS were 84.9% and 42.5%, respectively. On univariate analysis, STR was associated with inferior survival from salvage SRS (P ≤ 0.05). The 6- and 12-month local control (LC) estimates were 63.1% and 16.4%, respectively. On univariate analysis, higher biological effective dose and prior temozolomide were associated with superior LC. Concerning toxicity, there were 4 (12%) grade 2 and 1 (3%) grade 3 adverse events within this patient series. No grade 4 or grade 5 toxicities were observed. CONCLUSION: Our outcomes suggest that SRS is a feasible treatment option with acceptable salvage survival rates, given the poor prognosis of this disease.