The object of this study was to assess outcomes in patients with arteriovenous malformations (AVMs) treated by Gamma Knife stereotactic radiosurgery (SRS); lesions were stratified by size, ...symptomatology, and Spetzler-Martin (S-M) grade.
The authors performed a retrospective analysis of 102 patients treated for an AVM with single-dose or staged-dose SRS between 1993 and 2004. Lesions were grouped by S-M grade, as hemorrhagic or nonhemorrhagic, and as small (< 3 cm) or large (≥ 3 cm). Outcomes included death, morbidity (new neurological deficit, new-onset seizure, or hemorrhage/rehemorrhage), nidus obliteration, and Karnofsky Performance Scale score.
The mean follow-up was 8.5 years (range 5-16 years). Overall nidus obliteration (achieved in 75% of patients) and morbidity (19%) correlated with lesion size and S-M grade. For S-M Grade I-III AVMs, nonhemorrhagic and hemorrhagic combined, treatment yielded obliteration rates of 100%, 89%, and 86%, respectively; high functional status (Karnofsky Performance Scale Score ≥ 80); and 1% mortality. For S-M Grade IV and V AVMs, outcomes were less favorable, with obliteration rates of 54% and 0%, respectively. The AVMs that were not obliterated had a mean reduction in nidus volume of 69% (range 35%-96%). On long-term follow-up, 10% of patients experienced hemorrhage/rehemorrhage (6% mortality rate), which correlated with lesion size and S-M grade; the mean interval to hemorrhage was 81 months.
For patients with S-M Grade I-III AVMs, SRS offers outcomes that are favorable and that, except for the timing of obliteration, appear to be comparable to surgical outcomes reported for the same S-M grades. Staged-dose SRS results in lesion obliteration in half of patients with S-M Grade IV lesions.
Weekly paclitaxel, concurrent radiation, and androgen deprivation (ADT) were evaluated in patients with high-risk prostate cancer (PC) with or without prior prostatectomy (RP).
Eligible post-RP ...patients included: pathological T3 disease, or rising prostate-specific antigen (PSA) ≥ 0.5 ng/mL post-RP. Eligible locally advanced PC (LAPC) patients included: 1) cT2b-4N0N+, M0; 2) Gleason score (GS) 8-10; 3) GS 7 + PSA 10-20 ng/mL; or 4) PSA 20-150 ng/mL. Treatment included ADT (4 or 24 months), weekly paclitaxel (40, 50, or 60 mg/m(2)/wk), and pelvic radiation therapy (total dose: RP = 64.8 Gy; LAPC = 70.2 Gy).
Fifty-nine patients were enrolled (LAPC, n = 29; RP, n = 30; ADT 4 months, n = 29; 24 months, n = 30; whites n = 29, African Americans AA, n = 28). Baseline characteristics (median range) were: age 67 (45-86 years), PSA 5.9 (0.1-92.1 ng/mL), GS 8 (6-9). At escalating doses of paclitaxel, 99%, 98%, and 95% of doses were given with radiation and ADT, respectively, with dose modifications required primarily in RP patients. No acute Grade 4 toxicities occurred. Grade 3 toxicities were diarrhea 15%, urinary urgency/incontinence 10%, tenesmus 5%, and leukopenia 3%. Median follow-up was 75.3 months (95% CI: 66.8-82.3). Biochemical progression occurred in 24 (41%) patients and clinical progression in 11 (19%) patients. The 5- and 7-year OS rates were 83% and 67%. There were no differences in OS between RP and LAPC, 4- and 24-month ADT, white and AA patient categories.
In addition to LAPC, to our knowledge, this is the first study to evaluate concurrent chemoradiation with ADT in high-risk RP patients. With a median follow-up of 75.3 months, this trial also represents the longest follow-up of patients treated with taxane-based chemotherapy with EBRT in high-risk prostate cancer. Concurrent ADT, radiation, and weekly paclitaxel at 40 mg/m(2)/week in RP patients and 60 mg/m(2)/week in LAPC patients is feasible and well-tolerated.
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Summary
Marizomib, a natural marine product, is an irreversible proteasome inhibitor currently under investigation in relapsed‐refractory multiple myeloma (RRMM) and malignant glioma. Central nervous ...system‐multiple myeloma (CNS‐MM) is a rare manifestation of extra‐medullary disease with few therapeutic options, highlighting the unmet clinical need in these patients. Marizomib demonstrated encouraging activity in RRMM and has emerging clinical activity in glioma, making it a potential CNS‐MM therapeutic intervention. Herein, we present two patients with RRMM and CNS involvement who benefited from marizomib‐based therapy. These cases provide the first proof of principle for further exploring marizomib in CNS‐MM patients.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Stereotactic radiosurgery (SRS) has become a minimally invasive treatment modality for patients with refractory trigeminal neuralgia. It is unclear, however, how best to treat patients with pain that ...is refractory or recurrent after initial SRS. We report on treatment outcomes and quality of life for patients treated with repeated SRS for refractory or recurrent trigeminal neuralgia.
Between June 1996 and June 2001, 112 patients with trigeminal neuralgia were treated with SRS at the University of Maryland Medical Center. Eighteen patients underwent repeat SRS 3–42 months (median, 8 months) after initial radiosurgery because of unsatisfactory or unsustained pain relief. Patients received a median prescription dose of 75 and 70 Gy, respectively, for the first and second treatments. Self-reports of pain control were assessed with a standard questionnaire containing the complete Barrow Neurologic Institute Pain Scale.
The median follow-up was 37.5 months (range, 12–68 months) after initial SRS and 24.5 months (range, 6–65 months) after repeat SRS. For the 18 patients in this series, the percentage of patients reporting excellent, good, fair, and poor responses after the initial and repeat SRS was 50%, 28%, 6%, and 16% and 45%, 33%, 0%, and 22%, respectively. None of the 3 patients with pain refractory to initial SRS responded to repeat SRS. Among those with recurrent pain after initial SRS, 14 patients (93%) achieved excellent or good pain outcomes after repeat SRS. The actuarial analysis revealed a 1-year recurrence rate of 22%, with no patients reporting recurrent pain after 9 months of follow-up. Two patients (11%) reported new or increased facial numbness after retreatment, which was described as bothersome by one. Repeat SRS resulted in a median 60% improvement in quality of life, and 56% of patients believed that the procedure was successful.
Despite a modest dose reduction, repeat SRS provided similar rates of complete pain control as the initial procedure, but was not effective for patients with no response to initial treatment. Repeat SRS was more efficacious for those patients who experienced longer periods of pain relief after the initial SRS. The incidence of complications was not significantly different from that observed for initial SRS. In this series, most patients had significant improvements in quality of life.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
To assess efficacy and quality of life (QOL) outcomes associated with gamma-knife radiosurgery (GK-RS) in treating atypical trigeminal neuralgia (ATN) compared with classic trigeminal neuralgia ...(CTN).
Between September 1996 and September 2004, 35 cases of ATN were treated with GK-RS. Patients were categorized into two groups: Group I comprised patients presenting with ATN (57%); Group II consisted of patients presenting with CTN then progressing to ATN (43%). Median prescription dose 75 Gy (range, 70-80 Gy) was delivered to trigeminal nerve root entry zone. Treatment efficacy and QOL improvements were assessed with a standardized questionnaire.
With median follow-up of 29 months (range, 3-74 months), 72% reported excellent/good outcomes, with mean time to relief of 5.8 weeks (range, 0-24 weeks) and mean duration of relief of 62 weeks (range, 1-163 weeks). This rate of pain relief is similar to rate achieved in our previously reported experience treating CTN with GK-RS (p = 0.36). There was a trend toward longer time to relief (p = 0.059), and shorter duration of relief (p = 0.067) in patients with ATN. There was no difference in rate of, time to, or duration of pain relief between Groups I and II. Of the patients with ATN, 88% discontinued or decreased the use of pain medications. Among the patients with sustained pain relief, QOL improved an average of 85%.
This is the largest reported GK-RS experience for the treatment of ATN. Patients with ATN can achieve rates of pain relief similar to those in patients with CTN. Further follow-up is necessary to assess adequately the durability of response.
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26.
Radiation Oncology Emergencies Narang, Mannat; Mohindra, Pranshu; Mishra, Mark ...
Hematology/oncology clinics of North America,
02/2020, Volume:
34, Issue:
1
Journal Article
Peer reviewed
This article reviews the most common oncologic emergencies encountered by the radiation oncologist, including malignant spinal cord compression, intramedullary spinal cord metastasis, superior vena ...cava syndrome, hemoptysis, and airway compromise caused by tumor. Important trials evaluating different treatments for these emergencies are reviewed. The role of corticosteroids, surgery, chemotherapy, and radiation therapy in these patients is discussed and patient-specific treatment guidelines are suggested.
Phase 2 cooperative group meningioma trial assessing the safety and efficacy of risk-adaptive management strategies. This is the initial analysis of the high-risk cohort.
High-risk patients were ...those with a new or recurrent World Health Organization (WHO) grade III meningioma of any resection extent, recurrent WHO grade II of any resection extent, or new WHO grade II after subtotal resection. Patients received intensity-modulated radiotherapy (IMRT) using a simultaneous integrated boost technique (60 Gy high dose and 54 Gy low dose in 30 fractions). Three-year progression-free survival (PFS) was the primary endpoint. Adverse events (AEs) were scored per NCI Common Terminology Criteria for Adverse Events version 3.
Of 57 enrolled patients, 53 received protocol treatment. Median follow-up was 4.0 years (4.8 years for living patients). Two patients withdrew without progression before year 3; for the remaining 51 patients, 3-year PFS was 58.8%. Among all 53 protocol-treated patients, 3-year PFS was 59.2%. Three-year local control was 68.9%, and overall survival was 78.6%. Of 51 patients, 1 patient (1.9%) experienced a late grade-5 necrosis-related AE. All other acute (23 of 53 patients) and late (21 of 51 patients) AEs were grades 1 to 3.
Patients with high-risk meningioma treated with IMRT (60 Gy/30) experienced 3-year PFS of 58.8%. Combined acute and late AEs were limited to grades 1 to 3, except for a single necrosis-related grade 5 event. These results support postoperative IMRT for high-risk meningioma and invite ongoing investigations to improve outcomes further.
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TPS4615
Background: While a standard approach to muscle-invasive bladder cancer (MIBC) management involves neoadjuvant cisplatin-based chemotherapy (NAC) followed by radical cystectomy (RC), up to ...50% of pts recur with metastatic disease. Moreover, removal of the bladder has a significant impact on pts’ quality of life. Pathologic downstaging to non-muscle-invasive disease (<pT2) or complete response (pT0) at RC is associated with long-term survival benefit. Somatic DDR gene alterations were shown to be enriched in pts who were pT0 at RC following NAC in multiple retrospective analyses. We hypothesize that MIBC pts with somatic loss-of-function alterations within specific DDR genes and clinical responses to NAC can be uniquely managed with a bladder-sparing approach consisting of close cystoscopic and radiographic surveillance, avoiding the toxicities of definitive local therapy. Methods: A031701 is a multicenter phase II trial that will enroll 271 pts with T2-T4aN0/xM0 MIBC diagnosed within 60 days prior to enrollment. Multifocal MIBC, tumors >5 cm by cystoscopic assessment, and Bacillus Calmette-Guérin (BCG)-refractory disease (beyond standard induction and maintenance) are not allowed. Intravesical chemotherapy is allowed. Pts must be eligible for cisplatin chemotherapy. Eligible pts will receive either standard dose or dose dense gemcitabine and cisplatin chemotherapy (investigator’s choice) with simultaneous genetic sequencing of pre-treatment transurethral resection specimens. Pts whose tumors contain deleterious alterations in any 1 of 9 pre-selected DDR genes ( ERCC2, ERCC5, BRCA1, BRCA2, RECQL4, RAD51C, ATM, ATR, and FANCC) and who exhibit <T1 response on clinical restaging are eligible for organ-sparing management. Pts without deleterious DDR gene alterations or with >T1 disease after NAC will undergo RC or chemoradiation therapy (investigator/patient choice). The primary endpoint is 3-year event-free survival in DDR-altered pts who undergo bladder sparing, defined as the proportion of pts without BCG-unresponsive non-muscle invasive recurrences, any >T2 recurrences, or any metastatic recurrences. Secondary endpoints include clinical response rate (<cT1) in patients with deleterious DDR gene alterations following NAC, bladder-intact survival, overall survival, pT0 rate in DDR-altered pts who elect to undergo RC, pT0 rate in pts without DDR gene alterations, 3-year RC rate in pts with DDR gene alterations, and proportion of pts undergoing intravesical management for in-bladder recurrences. The study opened for enrollment in September 2018. Support: U10CA180821, U10CA180882. Clinical trial information: NCT03609216.
Histopathology and clinical staging have historically formed the backbone for allocation of treatment decisions in oncology. Although this has provided an extremely practical and fruitful approach ...for decades, it has long been evident that these data alone do not adequately capture the heterogeneity and breadth of disease trajectories experienced by patients. As efficient and affordable DNA and RNA sequencing have become available, the ability to provide precision therapy has become within grasp. This has been realized with systemic oncologic therapy, as targeted therapies have demonstrated immense promise for subsets of patients with oncogene-driver mutations. Further, several studies have evaluated predictive biomarkers for response to systemic therapy within a variety of malignancies. Within radiation oncology, the use of genomics/transcriptomics to guide the use, dose, and fractionation of radiation therapy is rapidly evolving but still in its infancy. The genomic adjusted radiation dose/radiation sensitivity index is one such early and exciting effort to provide genomically guided radiation dosing with a pan-cancer approach. In addition to this broad method, a histology specific approach to precision radiation therapy is also underway. Herein we review select literature surrounding the use of histology specific, molecular biomarkers to allow for precision radiotherapy with the greatest emphasis on commercially available and prospectively validated biomarkers.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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