Early outcomes of MR-guided SBRT for patients with recurrent pancreatic adenocarcinoma.

BACKGROUND: Local treatment options for locally recurrent pancreatic adenocarcinoma (LR-PAC) are limited, with median survival time (MST) of 9-13 months (mos) following recurrence. MRI-guided stereotactic body radiation therapy (MRgSBRT) provides the ability to dose escalate while sparing normal tissue. Here we report on the early outcomes of MRgSBRT for LR-PAC. METHODS: Patients with prior resection of pancreatic adenocarcinoma with local recurrence treated with MRgSBRT at a single tertiary referral center from 5-2021 to 2-2023 were identified from our prospective database. MRgSBRT was delivered to 40-50 Gy in 4-5 fractions with target and OAR delineation per institutional standards. Endpoints included local control per RECIST v1.1, distant failure, overall survival (OS), and acute and chronic toxicities per Common Terminology Criteria for Adverse Events, v5. RESULTS: Fifteen patients with LR-PAC were identified with median follow-up of 10.6 mos (2.8-26.5 mos) from MRgSBRT. There were 8 females and 7 males, with a median age of 69 years (50-83). One patient underwent neoadjuvant radiation for 50.4 Gy in 28 fractions followed by resection, and one underwent adjuvant radiation for 45 Gy in 25 fractions prior to recurrence. MRgSBRT was delivered a median of 18.8 mos (3.5-52.8 mos) following resection. OS following recurrence at 6 and 12 mos were 87% and 51%, respectively, with a median survival time of 14.1 mos (3.2-27.4 mos). Three patients experienced local failure at 5.9, 7.8, and 16.6 months from MgSBRT with local control of 92.3% and 83.9% at 6 and 12 months. 10 patients experienced distant failure at a median of 2.9 mos (0.3-6.7 mos). Grade 1-2 acute GI toxicity was noted in 47% of patients, and chronic GI toxicity in 31% of patients. No grade > 3 toxicities were noted. CONCLUSIONS: This is the first report on toxicity and outcomes of MRgSBRT for LR-PAC in the literature. MRgSBRT is a safe, feasible treatment modality with the potential for improved local control in this vulnerable population. Future research is necessary to better identify which patients yield the most benefit from MRgSBRT, which should continue to be used with systemic therapy as tolerated. TRIAL REGISTRATION: Jefferson IRB#20976, approved 2/17/21.

Long-Term Outcomes of Surgery and Radiation Treatment for Adult Patients with Craniopharyngioma.

OBJECTIVE: Treatment of craniopharyngioma typically entails gross total resection (GTR) or subtotal resection with adjuvant radiation (STR-RT). We analyzed outcomes in adults with craniopharyngioma undergoing GTR versus STR-RT. METHODS: This retrospective study enrolled 115 patients with craniopharyngioma in 5 institutions. Patients with STR received postoperative RT with stereotactic radiosurgery or fractionated radiation therapy per institutional preference and ability to spare optic structures. RESULTS: Median age was 44 years (range, 19-79 years). GTR was performed in 34 patients and STR-RT was performed in 81 patients with median follow-up of 78.9 months (range, 1-268 months). For GTR, local control was 90.5% at 2 years, 87.2% at 3 years, and 71.9% at 5 years. For STR-RT, local control was 93.6% at 2 years, 90.3% at 3 years, and 88.4% at 5 years. At 5 years following resection, there was no difference in local control (P = 0.08). Differences in rates of visual deterioration or panhypopituitarism were not observed between GTR and STR-RT groups. There was no difference in local control in adamantinomatous and papillary craniopharyngioma regardless of treatment. Additionally, worse local control was found in patients receiving STR-RT who were underdosed with fractionated radiation therapy (P = 0.03) or stereotactic radiosurgery (P = 0.04). CONCLUSIONS: Good long-term control was achieved in adults with craniopharyngioma who underwent STR-RT or GTR with no significant difference in local control. First-line treatment for craniopharyngioma should continue to be maximal safe resection followed by RT as needed to balance optimal local control with long-term morbidity.

Factors influencing local control after MR-guided stereotactic body radiotherapy (MRgSBRT) for adrenal metastases.

Purpose: Stereotactic body radiotherapy (SBRT) is an effective treatment for adrenal gland metastases, but it is technically challenging and there are concerns about toxicity. We performed a multi-institutional pooled retrospective analysis to study clinical outcomes and toxicities after MR-guided SBRT (MRgSBRT) using for adrenal gland metastases. Methods and Materials: Clinical and dosimetric data of patients treated with MRgSBRT on a 0.35 T MR-Linac at 11 institutions between 2016 and 2022 were analyzed. Local control (LC), local progression-free survival (LPFS), distant progression-free survival (DPFS) and overall survival (OS) were estimated using Kaplan-Meier method and log-rank test. Results: A total of 255 patients (269 adrenal metastases) were included. Metastatic pattern was solitary in 25.9 % and oligometastatic in 58.0 % of patients. Median total dose was 45 Gy (range, 16-60 Gy) in a median of 5 fractions, and the median BED10 was 100 Gy (range, 37.5-132.0 Gy). Adaptation was done in 87.4 % of delivered fractions based on the individual clinicians' judgement. The 1- and 2- year LPFS rates were 94.0 % (95 % CI: 90.7-97.3 %) and 88.3 % (95 % CI: 82.4-94.2 %), respectively and only 2 patients (0.8 %) experienced grade 3 + toxicity. No local recurrences were observed after treatment to a total dose of BED10 > 100 Gy, with single fraction or fractional dose of > 10 Gy. Conclusions: This is a large retrospective multi-institutional study to evaluate the treatment outcomes and toxicities with MRgSBRT in over 250 patients, demonstrating the need for frequent adaptation in 87.4 % of delivered fractions to achieve a 1- year LPFS rate of 94 % and less than 1 % rate of grade 3 + toxicity. Outcomes analysis in 269 adrenal lesions revealed improved outcomes with delivery of a BED10 > 100 Gy, use of single fraction SBRT and with fraction doses > 10 Gy, providing benchmarks for future clinical trials.

Differences in clinical outcomes based on molecular markers in glioblastoma patients treated with concurrent tumor-treating fields and chemoradiation: exploratory analysis of the SPARE trial.

BACKGROUND: Glioblastoma (GBM) is the most common primary malignant brain tumor in adults. Despite enormous research efforts, GBM remains a deadly disease. The standard-of-care treatment for patients with newly diagnosed with GBM as per the National Cancer Comprehensive Cancer Network (NCCN) is maximal safe surgical resection followed by concurrent chemoradiation and maintenance temozolomide (TMZ) with adjuvant tumor treating fields (TTF). TTF is a non-pharmacological intervention that delivers low-intensity, intermediate frequency alternating electric fields that arrests cell proliferation by disrupting the mitotic spindle. TTF have been shown in a large clinical trial to improve patient outcomes when added to radiation and chemotherapy. The SPARE trail (Scalp-sparing radiation with concurrent temozolomide and tumor treating fields) evaluated adding TTF concomitantly to radiation and chemotherapy. METHODS: This study is an exploratory analysis of the SPARE trial looking at the prognostic significance of common GBM molecular alterations, namely MGMT, EGFR, TP53, PTEN and telomerase reverse transcriptase (TERT), in this cohort of patients treated with concomitant TTF with radiation and chemotherapy. RESULTS: As expected, MGMT promoter methylation was associated with improved overall survival (OS) and progression-free survival (PFS) in this cohort. In addition, TERT promoter mutation was associated with improved OS and PFS in this cohort as well. CONCLUSIONS: Leveraging the molecular characterization of GBM alongside advancing treatments such as chemoradiation with TTF presents a new opportunity to improve precision oncology and outcomes for GBM patients.

Hemangioblastoma with late leptomeningeal metastasis: a case report.

BACKGROUND: Hemangioblastoma of the central nervous system is an uncommon benign neoplasm, with about 25% of cases in patients with von Hippel-Lindau disease. The incidence of metastasis is rare, particularly in patients without von Hippel-Lindau disease. We report a case of hemangioblastoma with leptomeningeal dissemination as a late recurrence. CASE PRESENTATION: A 65-year-old Caucasian man with a history of World Health Organization grade I hemangioblastoma of the cerebellar vermis underwent gross total resection in 1997. In early 2018, he developed intracranial recurrences with diffuse leptomeningeal disease of the entire spine. The patient underwent resection of intracranial recurrence, followed by palliative craniospinal irradiation. The disease progressed quickly, and he died 8 months after recurrence. CONCLUSIONS: Despite a benign pathology, hemangioblastoma has a low risk of metastasis. The outcome for hemangioblastoma patients with metastasis is poor. Multidisciplinary care for patients with metastatic hemangioblastoma warrants further investigation, and an effective systemic option is urgently needed. Regular lifelong follow-up of at-risk patients is recommended.

Tumor treating fields with radiation for glioblastoma: a narrative review.

BACKGROUND AND OBJECTIVE: With a phase 3 clinical trial (EF-32, ClinicalTrials.gov: NCT04471844) currently underway examining the potential benefit of concurrent chemoradiation and tumor treating fields (TTFields) for patients with glioblastoma (GBM), we present the following narrative review to highlight the current evidence that supports this approach. The current management paradigm for GBM includes maximal safe surgical resection followed by concurrent chemoradiation with further temozolomide (TMZ) and TTFields used as maintenance therapy. Despite several treatment advances over the past few decades, the overall prognosis remains poor and new strategies are currently under investigation, including the use of chemoradiation concurrently with TTFields. METHODS: In this review, we will discuss the preclinical and clinical work that has been performed combining both TTFields with radiation. We performed a narrative review of peer-reviewed articles related to the management of glioblastoma with regard to concurrent chemoradiation and TTFields and synthesized the data in the context of our clinical experience and practice. PubMed, Medline, Embase, Cochrane Library, and various center-specific guidelines were searched for literature regarding concurrent chemoradiation with TTFields for patients with GBM. KEY CONTENT AND FINDINGS: Driven by preclinical studies demonstrating the synergy between TTFields and radiation, more recent clinical work has been performed and has shown that combining treatment is both feasible and tolerable. CONCLUSIONS: In this review, we will discuss the mechanism of action which TTFields and radiation share, as well as discuss the toxicities of combining therapy in patients with GBM. Based on institutional experiences, we will highlight treatment techniques, including scalp sparing methodology and modified computed tomography (CT) simulation workflow, when concurrent TTFields and radiation are given. Lastly, we will provide discuss management considerations, specifically scalp prophylactic interventions and treatments, when using concurrent TTFields with chemoradiation.

Overcoming the cardiac toxicities of cancer therapy immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICIs) have led recent advances in the field of cancer immunotherapy improving overall survival in multiple malignancies with abysmal prognoses prior to their introduction. The remarkable efficacy of ICIs is however limited by their potential for systemic and organ specific immune-related adverse events (irAEs), most of which present with mild to moderate symptoms that can resolve spontaneously, with discontinuation of therapy or glucocorticoid therapy. Cardiac irAEs however are potentially fatal. The understanding of autoimmune cardiotoxicity remains limited due to its rareness. In this paper, we provide an updated review of the literature on the pathologic mechanisms, diagnosis, and management of autoimmune cardiotoxicity resulting from ICIs and their combinations and provide perspective on potential strategies and ongoing research developments to prevent and mitigate their occurrence.

Single-Dose Radiation Therapy Without Additional Surgery as a Treatment for Heterotopic Ossification Developing After Transfemoral Amputation.

ABSTRACT: Heterotopic ossification is the development of mature lamellar bone in soft tissues. Heterotopic ossification can occur in up to 23% of patients after amputation. Heterotopic ossification is often painful, causing significant dysfunction. While radiotherapy is used to prevent heterotopic ossification before formation, there is a dearth of literature on using radiotherapy to treat existing heterotopic ossification. This case report describes the use of late radiotherapy for the management of existing heterotopic ossification that developed after a transfemoral amputation. A 61-yr-old woman with peripheral artery disease of her bilateral lower limbs status post stenting and ultimately left transfemoral amputation was diagnosed with symptomatic heterotopic ossification limiting her function. Another surgery was not felt to be warranted. She was not improving with medical therapy and was prescribed 800 cGy in one fraction. After treatment, she experienced significant relief in her pain, allowing her to resume physical therapy and use of her prosthesis. There are no other published examples of using radiation alone for treatment of heterotopic ossification formation after transfemoral amputation without surgical revision of the bone formation. Our case shows possible utility in single-dose radiation as a treatment to prevent progression of heterotopic ossification, especially when limiting functional progress.

Thermoplastic Mask-Induced Contact Dermatitis: A Case Report.

Thermoplastic masks are commonly used in radiation therapy to immobilize a patient's head and neck during treatment. They are primarily composed of non-toxic polyester compounds that can be manipulated with heat to mold the shape of a patient's head and neck. There is little previously reported evidence of these masks causing allergic contact dermatitis. We present a case of a 44-year-old female with a history of squamous cell carcinoma of the right tonsil with multiple enlarged lymph nodes following surgical excision of the right tonsillar mass and ipsilateral neck dissection elected to undergo adjuvant radiation therapy with volumetric modulated arc therapy (VMAT) technique without concurrent chemotherapy. A thermoplastic mask was issued prior to radiation therapy. Following the mask fitting, the patient developed an allergic contact dermatitis reaction of the head and neck in areas covered by the mask. Her symptoms worsened with continued use of the thermoplastic mask and radiation therapy. As the patient continued and eventually finished the radiation treatment regimen, the dermatologic symptoms failed to respond to topical facial moisturizer and steroid treatment. The contact dermatitis reaction did not completely dissipate until about three months following completion of radiation therapy and contact with the thermoplastic mask. Thermoplastic masks are not known to cause an allergic contact dermatitis reaction. There is only one other reported case documented in the literature. Such reactions can alter the course of radiation therapy if symptoms are severe enough to disrupt treatment or if they cause worsening of the radiation dermatitis. Allergic contact dermatitis to thermoplastic masks should be well documented in the future to better understand the cause and possible risk factors related to the reaction.

Predictive Factors for Return to Driving following Volar Plate Fixation of Distal Radius Fracture.

Background A common query by patients undergoing distal radius fracture (DRF) repair is when (s)he can resume driving postoperatively. A prospective cohort analysis was performed to assess fracture and patient factors on a patient's self-reported ability to return to driving to better inform patients and surgeons. Methods Consecutive patients undergoing DRF repair with locking volar plate were enrolled. Preoperative demographic and radiographic characteristics, and postoperative time to return to driving were collected. Data collected included age, sex, hand dominance, body mass index (BMI), level of education, concomitant ulnar fracture, fracture setting prior to surgery, and AO fracture classification. Results A total of 131 patients were enrolled (108 women, 23 men) with 36 AO type A, 22 AO type B, and 73 AO type C DRFs, with an average age of 59.5 years. Fracture severity by classification did not significantly affect time to return to driving. However, BMI, sex, and age were found to significantly affect time to return to driving. Patients aged 19 to 59 years, 60 to 75 years, and over 75 years returned to driving 13.1, 15.4, and 30.1 days following surgery, respectively ( p < 0.01). Classified by BMI, patients that were normal weight, overweight, and obese returned to driving 11.5, 13.1, and 21.0 days following surgery, respectively ( p < 0.05). Men returned to driving 8.8 days and women 17.3 days postoperatively ( p = 0.001). Conclusion Patients severity of fracture as determined by AO fracture type did not affect time to driving, while increased BMI, female sex, and increased age were found to be significant factors in patients' return to driving time after distal radius fracture repair. Level of Evidence This is a Level II, prospective cohort study.

Splinting after Distal Radius Fracture Fixation: A Prospective Cohort Analysis of Postoperative Plaster Splint versus Soft Dressing.

Background The effect of postoperative dressing and splinting after distal radius fracture (DRF) open reduction internal fixation (ORIF) is not well understood. A prospective cohort analysis was performed to assess differences in functional and radiographic outcomes with the use of plaster splinting or soft dressing following DRF ORIF. Methods All patients undergoing DRF ORIF with locking volar plates were consecutively enrolled. Preoperative demographic and postoperative radiographic and functional outcome data were collected at 2 weeks and 3 months postoperatively. Functional data included range of motion (ROM), pain on visual analog scale (VAS), Patient-Rated Wrist Evaluation (PRWE), and quick Disabilities of the Arm, Shoulder and Hand (DASH) scores. Radiographic data included loss of fracture reduction. Results A total of 139 patients were enrolled (79 plaster splinting, 60 soft dressing). By the first postoperative visit (POV), there was one case of loss of reduction with plaster splinting and one case with soft dressing with no hardware failure or revision surgery in either group, and no difference in DASH, PRWE, or VAS pain scores. By the final POV, the soft dressing group showed greater ROM in extension by 9.6, flexion by 10.9, and supination by 4.8 degrees over plaster splinting. Additionally, the soft dressing group demonstrated statistically significant improvement in PRWE and DASH scores, as well as VAS pain scores as compared with plaster splinting. Conclusions Applying only soft dressing following DRF ORIF demonstrated improvements in ROM, VAS, and functional outcomes by final follow-up, with no significant differences in radiographic outcomes. No benefit of applying a plaster splint was identified.