Summary Twenty-eight patients with advanced life-threatening metastatic malignant melanoma were treated with high dose (140-260mgm-2) intravenous melphalan and autologous bone marrow. Cyclophosphamide "(priming" 300mgm-2 i.v. was given to 19 patients one week previously and this resulted in clinical but not histological evidence of amelioration of gastrointestinal toxicity. In 11 patients (43%) there was evidence of tumour response to treatment and in 2 patients complete remissions were observed. However in most patients, responses were short-lived and no patient lived longer than 17 months from start of treatment or 24 months from first recorded evidence of distant metastatic disease.

Background: Progressive collapsing foot deformity (PCFD) is recognized as a 3-dimensional deformity centered around the talus. Previous studies have described some features of talar motion in the ankle mortise in PCFD, such as sagging in the sagittal plane or valgus tilt in the coronal plane. However, axial plane alignment of the talus in the ankle mortise in PCFD has not been investigated extensively. The purpose of this study was to examine this axial plane alignment of PCFD vs controls using weightbearing computed tomography (WBCT) images and to determine if talar rotation in the axial plane is associated with increased abduction deformity, as well as to assess the medial ankle joint space narrowing in PCFD that may be associated with axial plane talar rotation. Methods: Multiplanar reconstructed WBCT images of 79 patients with PCFD and 35 control patients (39 scans) were retrospectively analyzed. The PCFD group was divided into 2 subgroups depending on preoperative talonavicular coverage angle (TNC): moderate abduction (TNC 20-40 degrees, n=57) and severe abduction (TNC >40 degrees, n=22). Using the transmalleolar (TM) axis as a reference, the axial alignment of the talus (TM-Tal), calcaneus (TM-Calc), and second metatarsal (TM-2MT) were calculated. Difference between TM-Tal and TM-Calc was calculated to examine talocalcaneal subluxation. A second method to assess talar rotation within the mortise utilized an angle between the lateral malleolus and the talus (LM-Tal) in the axial slices of WBCT. In addition, the prevalence of medial tibiotalar joint space narrowing was assessed. These parameters were compared between the control and PCFD groups, and between moderate and severe abduction groups. Results: The talus was significantly more internally rotated with respect to the ankle TM axis and the lateral malleolus in PCFD patients compared to controls, and in the severe abduction group compared with the moderate abduction group, using both measurement methods. Axial calcaneal orientation did not differ between groups. There was significantly greater axial talocalcaneal subluxation in the PCFD group, and this was also greater in the severe abduction group. The prevalence of medial joint space narrowing was higher in PCFD patients. Conclusion: Our findings suggest that talar malrotation in the axial plane should be considered an underlying feature of abduction deformity in PCFD. The malrotation occurs in both the talonavicular and ankle joints. This rotational deformity should be corrected at the time of reconstructive surgery, especially in cases of severe abduction deformity. In addition, medial ankle joint narrowing was observed in PCFD patients, with a higher prevalence of medial ankle joint narrowing in those with severe abduction. Level of Evidence: Level III, case-control study.

ImportanceO6-methylguanine-DNA methyltransferase (MGMT [OMIM 156569]) promoter methylation (mMGMT) is predictive of response to alkylating chemotherapy for glioblastomas and is routinely used to guide treatment decisions. However, the utility of MGMT promoter status for low-grade and anaplastic gliomas remains unclear due to molecular heterogeneity and the lack of sufficiently large data sets.ObjectiveTo evaluate the association of mMGMT for low-grade and anaplastic gliomas with chemotherapy response.Design, Setting, and ParticipantsThis cohort study aggregated grade II and III primary glioma data from 3 prospective cohort studies with patient data collected from August 13, 1995, to August 3, 2022, comprising 411 patients: MSK-IMPACT, EORTC (European Organization of Research and Treatment of Cancer) 26951, and Columbia University. Statistical analysis was performed from April 2022 to January 2023.ExposureMGMT promoter methylation status.Main Outcomes and MeasuresMultivariable Cox proportional hazards regression modeling was used to assess the association of mMGMT status with progression-free survival (PFS) and overall survival (OS) after adjusting for age, sex, molecular class, grade, chemotherapy, and radiotherapy. Subgroups were stratified by treatment status and World Health Organization 2016 molecular classification.ResultsA total of 411 patients (mean [SD] age, 44.1 [14.5] years; 283 men [58%]) met the inclusion criteria, 288 of whom received alkylating chemotherapy. MGMT promoter methylation was observed in 42% of isocitrate dehydrogenase (IDH)–wild-type gliomas (56 of 135), 53% of IDH-mutant and non-codeleted gliomas (79 of 149), and 74% of IDH-mutant and 1p/19q-codeleted gliomas (94 of 127). Among patients who received chemotherapy, mMGMT was associated with improved PFS (median, 68 months [95% CI, 54-132 months] vs 30 months [95% CI, 15-54 months]; log-rank P < .001; adjusted hazard ratio [aHR] for unmethylated MGMT, 1.95 [95% CI, 1.39-2.75]; P < .001) and OS (median, 137 months [95% CI, 104 months to not reached] vs 61 months [95% CI, 47-97 months]; log-rank P < .001; aHR, 1.65 [95% CI, 1.11-2.46]; P = .01). After adjusting for clinical factors, MGMT promoter status was associated with chemotherapy response in IDH–wild-type gliomas (aHR for PFS, 2.15 [95% CI, 1.26-3.66]; P = .005; aHR for OS, 1.69 [95% CI, 0.98-2.91]; P = .06) and IDH-mutant and codeleted gliomas (aHR for PFS, 2.99 [95% CI, 1.44-6.21]; P = .003; aHR for OS, 4.21 [95% CI, 1.25-14.2]; P = .02), but not IDH-mutant and non-codeleted gliomas (aHR for PFS, 1.19 [95% CI, 0.67-2.12]; P = .56; aHR for OS, 1.07 [95% CI, 0.54-2.12]; P = .85). Among patients who did not receive chemotherapy, mMGMT status was not associated with PFS or OS.Conclusions and RelevanceThis study suggests that mMGMT is associated with response to alkylating chemotherapy for low-grade and anaplastic gliomas and may be considered as a stratification factor in future clinical trials of patients with IDH–wild-type and IDH-mutant and codeleted tumors.

Introduction: Solitary fibrous tumor/hemangiopericytoma (SFT/HPC) of the central nervous system (CNS) is a rare meningeal tumor. Given the absence of prospective or randomized data, there are no standard indications for radiotherapy. Recently, the NRG Oncology and EORTC cooperative groups successfully accrued and completed the first prospective trials evaluating risk-adapted adjuvant radiotherapy strategies for meningiomas. Using a similar framework, we sought to develop prognostic risk categories that may predict the survival benefit associated with radiotherapy, using two large national datasets. Methods: We queried the National Cancer Database (NCDB) and the Surveillance, Epidemiology, and End Results (SEER) databases for all newly diagnosed cases of SFT/HPC within the CNS. Risk categories were created, as follows: low risk—grade 1, with any extent of resection (EOR) and grade 2, with gross–total resection; intermediate risk—grade 2, with biopsy/subtotal resection; high risk—grade 3 with any EOR. The Kaplan–Meier method and Cox proportional hazards regressions were used to determine the association of risk categories with overall and cause-specific survival. We then determined the association of radiotherapy with overall survival in the NCDB, stratified by risk group. Results: We identified 866 and 683 patients from the NCDB and SEER databases who were evaluated, respectively. In the NCDB, the 75% survival times for low- (n = 312), intermediate- (n = 239), and high-risk (n = 315) patients were not reached, 86 months (HR 1.60 (95% CI 1.01–2.55)), and 55 months (HR 2.56 (95% CI 1.68–3.89)), respectively. Our risk categories were validated for overall and cause-specific survival in the SEER dataset. Radiotherapy was associated with improved survival in the high- (HR 0.46 (0.29–0.74)) and intermediate-risk groups (HR 0.52 (0.27–0.99)) but not in the low-risk group (HR 1.26 (0.60–2.65)). The association of radiotherapy with overall survival remained significant in the multivariable analysis for the high-risk group (HR 0.55 (0.34–0.89)) but not for the intermediate-risk group (HR 0.74 (0.38–1.47)). Similar results were observed in a time-dependent landmark sensitivity analysis. Conclusion: Risk stratification based on grade and EOR is prognostic of overall and cause-specific survival for SFT/HPCs of the CNS and performs better than any individual clinical factor. These risk categories appear to predict the survival benefit from radiotherapy, which is limited to the high-risk group and, potentially, the intermediate-risk group. These data may serve as the basis for a prospective study evaluating the management of meningeal SFT/HPCs.

Background: Digitally reconstructed radiographs (DRRs) generated from weightbearing computed tomography (WBCT) may potentially substitute for weightbearing plain radiographs (XRs) but have not been clinically validated. This study aims to test the reliability of 6 radiographic parameters of progressive collapsing foot deformity (PCFD) as measured on DRR, to investigate whether DRR represents comparably to XR through the same measurements, and to compare agreement of DRR and XR measurements of a standardized arch height parameter with reference measurements made on WBCT. Methods: DRR generated from preoperative WBCT of 71 patients (72 feet) treated surgically for PCFD were retrospectively compared with preoperative weight-bearing XR after exclusion criteria were applied. Six radiographic measurements were performed, including Meary angle, calcaneal pitch (CPA), medial cuneiform height (MCH), AP talar–first metatarsal angle (T-1MT), talonavicular coverage (TNCA), and talar incongruency (TIA). Arch height was measured on XR, DRR, and WBCT using a validated, standardized, navicular-based index. Intraclass correlation coefficients assessed DRR intraobserver and interobserver reliability. Paired samples t tests tested differences between XR and DRR. Bland-Altman limits of agreement analysis compared DRR and XR agreement with WBCT measurements. Results: Measurements were within standard PCFD ranges on XR and DRR. All measurements demonstrated excellent intrarater reliability and good to excellent interrater agreement, consistent with previous literature on XR. No differences were found for Meary, CPA, or TNCA. Minor differences were observed for MCH, T-1MT, and TIA. DRR measurements demonstrated greater agreement with WBCT than XR measurements. Conclusion: DRR from WBCT may be a promising substitute for XR in the clinical evaluation of PCFD. Radiographic measurements made on DRR demonstrated good to excellent reliability. Although small differences were found between XR and DRR for certain measurements, DRR more accurately represented medial arch anatomy compared to gold standard WBCT data than XR. If validated as a clinical substitute, DRR could eventually obviate XR where WBCT is available. Level of Evidence: Level III, retrospective cohort study.