Actuarial Progression-free Survival Research Articles

Stereotactic Body Radiation Therapy for Oligoprogressive Ovarian Cancer Patients Treated During Poly(ADP‐Ribose)‐Polymerase Inhibitor Maintenance: Efficacy and Adverse Events From the Epimetheo Retrospective Study

The aim of this observational, retrospective, multicenter study (Epimetheo) was to analyze the activity and the safety of stereotactic body radiation therapy (SBRT) during poly(ADP-ribose)-polymerase inhibitor (PARPi) maintenance in a series of oligometastatic ovarian cancer (OC) patients. Patients treated with PARPi in maintenance setting received SBRT if oligometastatic progression occurred. Maintenance treatment was continued until the extensive progression of the disease. The primary endpoints of the study were as follows: next systemic treatment change-free survival (NEST-FS) and acute and late toxicity; the secondary endpoints were as follows: the rate of clinical complete response (CR), the 2-year actuarial local control (LC, progression of disease inside SBRT field) rate on "per lesion" basis, the 2-year actuarial progression-free survival, and 2-year overall survival (OS). From April 2018 to September 2023, SBRT was used to treat 74 OC patients with a total of 158 lesions (98 lymph nodes and 60 parenchymal lesions) under PARPi maintenance. Olaparib, niraparib, and rucaparib were administered to 41.9%, 48.6%, and 9.5% of patients, respectively. CR, partial response, stable disease, and progressive disease were observed in 115 (72.8%), 32 (20.3%), 9 (5.7%), and 2 lesions (1.3%), respectively. Severe toxicities were reported in less than 3% of patients. The actuarial median NEST-FS was 10 months, with a range of 6.7-13.3 months. The 12- and 24-month actuarial NEST-FS rates were 44.9% and 31.4%, respectively. The 2-year actuarial LC, progression-free survival, and OS were 68.1%, 22.5%, and 77%, respectively with differences in figures between complete and incomplete responders. The achievement of CR was found to be correlated with an improvement in LC and OS. This study reports the activity and the low toxicity profile of SBRT in association with PARPi in oligometastatic OC patients. A rapid, minimally invasive, and cost-effective treatment such as SBRT may be proposed as a means of prolonging NEST-FS and maintaining an effective treatment regimen involving PARPi.

Use of Different Anti-PD-1 Checkpoint Combination Strategies for First-Line Advanced NSCLC Treatment-The Experience of Ion Chiricuță Oncology Institute.

Different combination modalities between an anti-PD-1/PD-L1 agent and a platinum-based chemotherapy or another checkpoint inhibitor (with or without a short course or full course of a platinum doublet) proved superior to chemotherapy alone in multiple clinical trials, but these strategies were not directly compared. The aim of this study is to report the real-world data results with different immunotherapy combinations in a series of patients treated in consecutive cohorts at the Ion Chiricuță Oncology Institute. A total of 122 patients were successively enrolled in three cohorts: (1A) nivolumab + ipilimumab (18 patients), (1B) nivolumab + ipilimumab + short-course chemotherapy (33 patients), and (2) pembrolizumab plus full-course chemotherapy (71 patients). Endpoints included overall survival (OS), progression-free survival (PFS), objective response (ORR), and univariate and multivariate exploratory analysis of prognostic factors. Median follow-up in the consecutive cohorts 1A, 1B, and 2 was 83 versus 59 versus 14.2 months. Median OS and PFS for all patients were 22.2 and 11.5 months, respectively, and 2-year actuarial OS and PFS were 49% and 35%, respectively. For the nivolumab + ipilimumab (cohorts 1A and 1B) versus pembrolizumab combinations (cohort 2), median OS was 14 vs. 24.8 months (p = 0.18) and 2-year actuarial survival 42% vs. 53%; median PFS was 8.6 vs. 12.7 months (p = 0.41) and 2-year actuarial PFS 34% vs. 35%; response rates were 33.3% vs. 47.9% (p = 0.22). Older age, impaired PS (2 versus 0-1), corticotherapy in the first month of immunotherapy, and >3.81 neutrophils to lymphocytes ratio were independent unfavorable prognostic factors in the multivariate analysis of survival (limited to 2 years follow-up). The 5-year long-term survival was 30.5% and 18.8% for cohorts 1A and 1B, respectively (not enough follow-up for cohort 2). Efficacy results using different immunotherapy combination strategies were promising and not significantly different between protocols at 2 years. Real-world efficacy and long-term results in our series were in line with those reported in the corresponding registration trials.

Long term follow-up of patients with newly diagnosed glioblastoma treated by intraoperative photodynamic therapy: an update from the INDYGO trial (NCT03048240)

PurposeGlioblastoma remains incurable despite optimal multimodal management. The interim analysis of open label, single arm INDYGO pilot trial showed actuarial 12-months progression-free survival (PFS) of 60% (median 17.1 months), actuarial 12-months overall survival (OS) of 80% (median 23.1 months). We report updated, exploratory analyses of OS, PFS, and health-related quality of life (HRQOL) for patients receiving intraoperative photodynamic therapy (PDT) with 5-aminolevulinic acid hydrochloride (5-ALA HCl).MethodsTen patients were included (May 2017 – April 2021) for standardized therapeutic approach including 5-ALA HCl fluorescence-guided surgery (FGS), followed by intraoperative PDT with a single 200 J/cm2 dose of light. Postoperatively, patients received adjuvant therapy (Stupp protocol) then followed every 3 months (clinical and cerebral MRI) and until disease progression and/or death. Procedure safety and toxicity occurring during the first four weeks after PDT were assessed. Data concerning relapse, HRQOL and survival were prospectively collected and analyzed.ResultsAt the cut-off date (i.e., November 1st 2023), median follow-up was 23 months (9,7–71,4). No unacceptable or unexpected toxicities and no treatment-related deaths occurred during the study. Kaplan–Meier estimated 23.4 months median OS, actuarial 12-month PFS rate 60%, actuarial 12-month, 24-month, and 5-year OS rates 80%, 50% and 40%, respectively. Four patients were still alive (1 patient free of recurrence).ConclusionAt 5 years-follow-up, intraoperative PDT with surgical maximal excision as initial therapy and standard adjuvant treatment suggests an increase of time to recurrence and overall survival in a high proportion of patients. Quality of life was maintained without any severe side effects.Trial registration NCT numberNCT03048240. EudraCT number: 2016–002706-39.

Real-world assessment of treatment multiple myeloma patients on the example of one hematology center

Relevance. Despite significant improvements in therapeutic options, patients with multiple myeloma (MM) experience a series of remissions and relapses requiring further lines of therapy, which requires the prescription of new lines of therapy. Methods. We analyzed the types and outcomes of treatment, attrition rates (AR) — the proportion of patients who dropped out of program therapy, and refractoriness to different lines of therapy (LOT) in 447 patients with MM between 2010 and 2022. Resalts. The AR was 17% between LOT-1 and LOT-2, 15% between LOT-2 and LOT-3, and 25% between LOT-3 and LOT- 4. In multivariate regression analysis, only high MM risk significantly increased AR risk. Each new progression of MM increased the number of patients with refractory to bortezomib, lenalidomide, or daratumumab. After LOT-1, LOT-2, and LOT-6%, 26%, and 53% of patients were double-refractory, respectively, and 54% were triple-refractory. Bortezomib- or lenalidomide-refractory patients had a 2.6-fold lower chance of achieving a very good partial response or better (VGPR+). From LOT-1 to LOT-4, the overall response rate and VGPR+ decreased from 74% and 53% to 25% and 15%, respectively. Overall survival (OS) in the entire population was 7.6 years, with an actuarial 5-year OS of 67% and a 10-year OS of 44%. The median of progression-free survival (PFS) was 20 months on LOT-1, 19 months on LOT-2, and 7 months on LOT-3, and the actuarial 5-year PFS was 25%, 18%, and 10%, respectively. Conclusions: In this regard, we observe a continuing trend in the use of cisplatin-containing "rescue" chemotherapy regimens, especially in patients with an aggressive course, including extramedullary forms of MM. These patients could be candidates for bispecific antibody therapy and CAR T-cell therapy, but these options are not yet available in Russia.

Dosimetric Analysis of Local Failure Outcomes and Vertebral Compression Fracture Risk in Single-Fraction Spine Stereotactic Radiosurgery for Metastatic Sarcoma

Sarcoma spinal metastases (SSM) are particularly difficult to manage given their poor response rates to chemotherapy and their inherent radioresistance. We sought to analyze dosimetric parameters impacting local failure and vertebral compression fracture outcomes in a homogenously treated cohort of patients with SSM treated with single-fraction spine stereotactic radiosurgery (SSRS). A retrospective review was conducted on a cohort of patients with SSM treated with definitive SSRS at a single tertiary institution. 16-24 Gy was delivered to the GTV and 16 Gy uniformly to the CTV. Kaplan-Meier analysis was conducted to assess time to local failure (LF). The log-rank test was utilized to examine group differences. Patients were censored at time of last follow-up or death. Cox proportionate hazards modeling was used to determine hazard ratios (HR) and their respective 95% confidence intervals (CI). A total of 66 patients with 96 lesions underwent SSRS for SSM. Median follow-up was 17 months (IQR 8-28). Median age was 55 years (IQR 41-63). The most common histological subtype was leiomyosarcoma (41%) followed by liposarcoma (9%). 81 lesions received 24 Gy to the GTV, 12 received 18 Gy and 3 received 16 Gy. Median GTV and CTV volume was 13.6cc (IQR 5-27) and 51.6cc (IQR 30-80) respectively. 27% of patients had Bilsky 1b or greater disease. 16 of 96 lesions demonstrated progression representing a crude local failure rate of 17% with median time to failure of 8 months (IQR 5-18). The 1-year actuarial progression free survival (PFS) was 89% with a median PFS of 13 months (IQR 16-63). Median overall survival (OS) was 15 months (IQR 8-28) from SSRS. 8% of patients developed vertebral compression fractures at a median of 13 months post SSRS (IQR 7-25). Every 1 Gy increase in GTV minimum dose (DMin) across the range (5.8-25cc) was associated with a reduced risk of local failure (HR = 0.875 [95% CI 0.787-0.974], p = 0.01). Stratifying thresholds for GTV DMin, a local control benefit was seen as low as 12 Gy and higher (HR = 0.329 [95% CI 0.11-0.97, p = 0.044) with a significantly greater magnitude benefit seen at 14 Gy (HR = 0.267 [95% CI 0.09-0.77, p = 0.014) and above 15 Gy (HR = 0.091 [95% CI 0.03-0.41], p = 0.0018). There were no other queried variables besides GTV Dmin associated with local control including: GTV: volume, mean, Dmax, D90, CTV: volume, Dmin, Dmean, Dmax, or D90. There was an increased risk of VCF with increasing CTV DMean (HR = 2.4 [95% CI 1.4-4.1], p = 0.002) and CTV D90 (HR = 2.2 [95% CI 1.2-4.0], p = 0.01); however, no association with GTV parameters. This study represents one of the most homogenously treated and the largest cohorts of patients with sarcoma spinal metastases treated with single-fraction SSRS. Despite inherent radioresistance, SSRS confers durable and high rates of local control in SSM without unexpected long-term toxicity rates. Increasing GTV minimum dose is significantly associated with superior local control with no corresponding increased risk of VCF.

Volumetric extent of resection and survival for recurrent atypical meningioma.

In recurrent atypical meningioma, the survival impact of volumetric extent of resection (vEOR) and residual tumor volume (RTV) has not been previously studied. The authors performed a retrospective vEOR analysis of patients with recurrent World Health Organization grade II meningiomas treated with reresection from 2000 to 2019. The Kaplan-Meier method and multivariate Cox regression analysis were used to study progression-free survival (PFS) and overall survival (OS). Fifty-nine patients with a median follow-up duration of 95 (95% CI 42-148) months were included. The median (range) vEOR was 100% (32%-100%) and the mean ± SD was 90.7% ± 15.3%. Among patients who underwent gross-total resection (GTR) (n = 32 [54%]), Simpson grade I and II resections were achieved in 23 (72%) and 9 (28%) patients, respectively. Among patients who underwent subtotal resection (n = 27 [46%]), the median (range) RTV was 4.3 (0.3-40) cm3. The 1-, 2-, and 5-year actuarial PFS rates for the cohort were 76%, 56%, and 34%, respectively. The 1-, 2-, and 5-year actuarial OS rates for the cohort were 98%, 78%, and 60%, respectively. Variables reflecting EOR significantly impacted both PFS and OS in multivariate analysis: GTR (p < 0.01) was significantly associated with longer PFS, and lower Simpson grade (p = 0.04) was significantly associated with longer OS. Additional factors including RTV, Ki-67 index, and pretreatment and posttreatment history also impacted survival outcomes (p < 0.05). EOR and Simpson grade were independently associated with survival outcomes in patients with recurrent atypical meningioma. These findings support the practice of thorough reresection for maximal cytoreduction in appropriate surgical candidates.

Efficacy and Safety of Stereotactic Body Radiation Therapy in Oligometastatic Uterine Cancer (MITO-RT2/RAD): A Large, Real-World Study in Collaboration With Italian Association of Radiation Oncology, Multicenter Italian Trials in Ovarian Cancer, and Mario Negri Gynecologic Oncology Group Groups

This retrospective, multicenter study analyzes the efficacy and safety of stereotactic body radiotherapy in a large cohort of oligometastatic/persistent/recurrent uterine cancer patients. Clinical and radiotherapy data from several radiotherapy centers treating patients by stereotactic body radiotherapy between March 2006 and October 2021 were collected. Objective response rate was defined as complete and partial response, while clinical benefit included objective response rate plus stable disease. Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer and Common Terminology Criteria for Adverse Events scales were used to grade toxicities. Primary endpoints were the rate of complete response to stereotactic body radiotherapy, and the 2-year actuarial local control rate 'per-lesion' basis. Secondary endpoints were progression-free survival and overall survival, as well as toxicity. 157 oligometastatic/persistent/recurrent uterine cancer patients bearing 272 lesions treated by stereotactic body radiotherapy at 14 centers were analyzed. Lymph node metastases (137, 50.4%) were prevalent, followed by parenchyma lesions (135, 49.6%). Median total dose was 35 Gy (10-75.2), in five fractions (range 1-10). Complete and partial responses were 174 (64.0%), and 54 (19.9%), respectively. Stable disease was registered in 29 (10.6%), while 15 (5.5%) lesions progressed. Type of lesion (lymph node), volume (≤ 13.7 cc) and total dose (BED10 >59.5 Gy) were significantly associated with a higher probability of achieving complete response. Patients achieving complete response (CR) 'per-lesion' basis experienced a 2-year actuarial local control rate of 92.4% versus 33.5% in lesions not achieving complete response (NCR) (p<0.001). Moreover, the 2-year actuarial progression-free survival rate in patients with CR was 45.4%, while patients with NCR had a 2-year rate of 17.6% (p value: <0.001). Finally, patients who had a CR had a 2-year overall survival rate of 82.7%, compared to 56.5% for NCR ONES (P VALUE: <0.001) . Severe acute toxicity was around 2%, including one toxic death due to gastric perforation, and severe late toxicity around 4%. The efficacy of stereotactic body radiotherapy in this setting was confirmed. The low toxicity profile and the high local control rate in complete responder patients encourage the wider use of this approach.

Carbon-ion radiotherapy in the treatment of radiation-induced second primary malignancies

Treatment of radiation-induced second primary malignancy (RI-SPM) is challenging and usually associated with poor outcomes. For patients with unresectable or incompletely resected diseases, carbon-ion radiotherapy (CIRT) offers physical and biologic advantages over photon-based re-irradiation. We report the results of salvage CIRT in 15 patients with RI-SPM. Fifteen consecutive and non-selected patients with RI-SPM who underwent salvage CIRT at the Shanghai Proton and Heavy Ion Center between November 2015 and May 2019 were included in this retrospective study. CIRT doses were 57.5-69 Gy (RBE) [at 2.5-3.0 Gy (RBE)/daily fraction]. The actuarial 1-year overall survival (OS), locoregional progression-free survival (LPFS), distant metastasis-free survival (DMFS), and progression-free survival (PFS) rates as well as acute/late toxicities were analyzed. Among the 15 patients included, 10 were soft tissue sarcomas, 2 were chondrosarcomas, 1 was osteosarcoma, 1 was squamous cell carcinoma and 1 was esthesioneuroblastoma. With a median follow-up of 13.0 (range, 2.73-29.63) months, the actuarial 1-year OS, LPFS, DMFS, and PFS rates were 69.3%, 53.0%, 92.9%, and 48.2%, respectively. No grade 2 and grade 3 acute adverse effect was observed. One patient experienced grade 4 hemorrhage which required embolization during CIRT, and lately died from hemorrhage (grade 5) at 3.4 months after the completion of CIRT. No other late adverse effects of ≥ grade 2 was observed. Salvage CIRT provided relatively safe and effective short-term outcome for patients with unresectable or in-completely resected RI-SPM, as compared to historical data on re-irradiation using the conventional photon beam technology. However, further improvement in both disease control and toxicity prevention is needed.

Stereotactic Radiosurgery for Benign Cavernous Sinus Meningiomas: A Multicentre Study and Review of the Literature.

Simple Summary Meningiomas are the most common tumours of the central nervous system (CNS). Despite their benign histology, proximity to critical neurovascular structures may lead to significant morbidity with tumour growth. This is the case for cavernous sinus meningiomas (CSMs), as their growth may surround critical neuro-vascular structures and cause significant morbidity. Radical microsurgical resection carries a high risk of additional neurological deficits, as well as the risk of death. Current management of these tumours, where treatment is indicated, has moved away from radical surgery towards radiotherapy/radiosurgery. This is particularly the case for patients who have residual or recurring tumours after previous surgery. There are many reports that describe the effectiveness of using stereotactic radiosurgery (SRS) for CSMs; however, large cohort analyses are lacking. This multicentre analysis reports the outcome data of over 1000 patients with CSMs who were treated with SRS. SRS shows a high local tumour control rate with few complications. These results agree with previous reports in the literature. SRS is a valuable primary or adjuvant treatment option for CSMs.Cavernous sinus meningiomas (CSMs) remain a surgical challenge due to the intimate involvement of their contained nerves and blood vessels. Stereotactic radiosurgery (SRS) is a safe and effective minimally invasive alternative for the treatment of small- to medium-sized CSMs. Objective: To assess the medium- to long-term outcomes of SRS for CSMs with respect to tumour growth, prevention of further neurological deterioration and improvement of existing neurological deficits. This multicentric study included data from 15 European institutions. We performed a retrospective observational analysis of 1222 consecutive patients harbouring 1272 benign CSMs. All were treated with Gamma Knife stereotactic radiosurgery (SRS). Clinical and imaging data were retrieved from each centre and entered into a common database. All tumours with imaging follow-up of less than 24 months were excluded. Detailed results from 945 meningiomas (86%) were then analysed. Clinical neurological outcomes were available for 1042 patients (85%). Median imaging follow-up was 67 months (mean 73.4, range 24–233). Median tumour volume was 6.2 cc (+/−7), and the median marginal dose was 14 Gy (+/−3). The post-treatment tumour volume decreased in 549 (58.1%), remained stable in 336 (35.6%) and increased in only 60 lesions (6.3%), yielding a local tumour control rate of 93.7%. Only 27 (2.8%) of the 60 enlarging tumours required further treatment. Five- and ten-year actuarial progression-free survival (PFS) rates were 96.7% and 90.1%, respectively. Tumour control rates were higher for women than men (p = 0.0031), and also for solitary sporadic meningiomas (p = 0.0201). There was no statistically significant difference in outcome for imaging-defined meningiomas when compared with histologically proven WHO Grade-I meningiomas (p = 0.1212). Median clinical follow up was 61 months (mean 64, range 6–233). Permanent morbidity occurred in 5.9% of cases at last follow-up. Stereotactic radiosurgery is a safe and effective method for treating benign CSM in the medium term to long term.

The Selective Personalized Radio-immunotherapy for Locally Advanced NSCLC Trial (SPRINT): Initial results.

8510 Background: Standard therapy for unresectable locally advanced non-small cell lung cancer (LA-NSCLC) is concurrent chemoradiotherapy followed by adjuvant durvalumab. We performed a prospective trial testing sequential pembrolizumab and risk-adapted radiotherapy without chemotherapy for biomarker-selected LA-NSCLC patients. Methods: Patients with stage III NSCLC or unresectable stage II NSCLC, ECOG performance status 0-1, and no contraindications to protocol-specified therapy were eligible for this trial. Subjects with PD-L1 tumor proportion score (TPS) ≥ 50% underwent baseline FDG-PET/CT, received three cycles of induction pembrolizumab (200 mg, every 21 days), underwent restaging FDG-PET/CT, received risk-adapted thoracic radiotherapy (55 Gy delivered to tumors or lymph nodes with metabolic tumor volume exceeding 20 cc and 48 Gy delivered to smaller lesions, all in 20 daily fractions), and then received up to 13 cycles of additional pembrolizumab. The primary study endpoint was one-year progression-free survival (PFS). Here we report response rates following induction pembrolizumab, PFS and overall survival (OS) rates, and adverse event rates (CTCAE v. 4.03). Results: Twenty-five subjects with PD-L1 TPS ≥ 50% from three institutions were enrolled between August 2018 and November 2021. Median age was 71 (interquartile range [IQR] 62 to 77). One subject had stage II disease, 13 had stage IIIA disease, nine had stage IIIB disease, and two had stage IIIC disease. Median PD-L1 TPS was 75% (IQR 60 to 80%). Two subjects (8%) developed disease progression during induction pembrolizumab, and two subjects discontinued pembrolizumab after one infusion due to immune-related adverse events. Using RECIST 1.1 criteria, 12 subjects (48%) exhibited a partial (n = 11) or complete (n = 1) response following induction pembrolizumab on CT. Using PERCIST criteria, 12 subjects (48%) exhibited a partial response following induction pembrolizumab on PET. Four subjects had responses on PET but not on CT, and four had responses on CT but not on PET. With a median follow-up duration of 13 months, the actuarial 1-year PFS rate is 74%, and the actuarial 1-year OS rate is 95%. Grade 3 adverse events have been limited to single cases of anemia, arthritis, diarrhea, esophagitis, and pneumonitis, and no grade 4-5 adverse events have occurred. Exploratory analyses suggest that response to induction pembrolizumab on PET predicts efficacy of this treatment approach, with a 1-year PFS rate of 100% for responders, compared to 61% for non-responders (logrank p = 0.007). Conclusions: Treatment with pembrolizumab and risk-adapted radiotherapy is a promising treatment approach for LA-NSCLC patients with PD-L1 TPS ≥ 50%. Response on PET following induction pembrolizumab may be useful for identifying patients who can be treated successfully without chemotherapy. Clinical trial information: NCT03523702.

Stereotactic body radiotherapy in oligometastatic cervical cancer (MITO-RT2/RAD study): a collaboration of MITO, AIRO GYN, and MaNGO groups

ObjectiveThis retrospective, multicenter study analyzes the efficacy and safety of stereotactic body radiotherapy in a large cohort of patients with oligometastatic/persistent/recurrent cervical cancer.MethodsA standardized data collection from several radiotherapy centers...

Taxane/gemcitabine-containing chemotherapy plus locoregional IMRT for patients with de novo metastatic nasopharyngeal carcinoma: the treatment outcomes and prognostic factors analysis

PurposeTo evaluate treatment outcomes of de novo metastatic nasopharyngeal carcinoma (mNPC) patients receiving taxane/gemcitabine-containing chemotherapy followed by locoregional intensity-modulated radiotherapy (IMRT) and analyze potential prognostic factors.MethodsA total of 118 patients between March 2008 and November 2018 were retrospectively analyzed. All the patients were treated with taxane/gemcitabine-containing systemic chemotherapy followed by definitive locoregional IMRT. Potential prognostic factors including baseline absolute lymphocyte count (ALC) and the subdivision of metastasis were analyzed.ResultsThe median follow-up time for the whole group was 31.5 months (range 5–138 months). Of the 118 patients, 9 (7.6%) patients experienced local regional failure and 60 (50.8%) patients had progression of distant metastasis. At the time of the last follow-up, 61 (51.7%) patients were dead. The 5-year actuarial progression free survival (PFS), overall survival (OS),distant metastasis relapse free survival (DMFS) and local regional recurrence free survival (LRFS) were 34.2%, 44%, 41.1% and 82.6%, respectively. Baseline lymphocyte count ≥ 1600/μl prior to the treatment conferred better locoregional control (5y-LRFS 96% vs. 64.7%, p < 0.001) and distant metastasis control (5y-MFS 50.4% vs. 32.4%, p = 0.023). The multivariate analysis showed that high lymphocyte count was the most relevant predictor of superior PFS (HR = 0.236, p < 0.001) and OS (HR = 0.518, p = 0.04). M subdivision was found as another independent prognostic factor for OS but not for PFS.ConclusionTaxane/gemcitabine-containing chemotherapy combined with IMRT represents an effective treatment modality for mNPC. Baseline ALC is an independent significant prognostic factor for PFS and OS.

Residual Tumor Volume and Tumor Progression after Subtotal Resection and Observation of WHO Grade I Skull Base Meningiomas

Objective This study investigated the impact of residual tumor volume (RTV) on tumor progression after subtotal resection and observation of WHO grade I skull base meningiomas. Study Design This study is a retrospective volumetric analysis. Setting This study was conducted at a single institution. Participants Patients who underwent subtotal resection of a WHO grade I skull base meningioma and postsurgical observation (July 1, 2007-July 1, 2017). Main Outcome Measure The main outcome was radiographic tumor progression. Results Sixty patients with residual skull base meningiomas were analyzed. The median (interquartile range) RTV was 1.3 (5.3) cm 3 . Tumor progression occurred in 23 patients (38.3%) at a mean duration of 28.6 months postsurgery. The 1-, 3-, and 5-year actuarial progression-free survival (PFS) rates were 98.3, 58.6, and 48.7%, respectively. The Cox multivariate analysis identified increasing RTV ( p = 0.01) and history of more than 1 previous surgery ( p = 0.03) as independent predictors of tumor progression. In a Kaplan-Meier analysis for PFS, the RTV threshold of 3 cm 3 maximized log-rank testing significance between groups of patients dichotomized at 0.5 cm 3 thresholds ( p < 0.01). The 3-year actuarial PFS rates for meningiomas with RTV ≤3 cm 3 and >3 cm 3 were 76.2 and 32.1%, respectively. When RTV >3 cm 3 was entered as a covariate in the Cox model, it was the only factor independently associated with tumor progression ( p < 0.01). Conclusion RTV was associated with tumor progression after subtotal resection of WHO grade I skull base meningioma in this cohort. An RTV threshold of 3 cm 3 was identified that minimized progression of the residual tumor when gross total resection was not safe or feasible.

503 - Long-Term Outcomes of Allogeneic Hematopoietic Cell Transplantation in Patients with Newly Diagnosed Multiple Myeloma

503 - Long-Term Outcomes of Allogeneic Hematopoietic Cell Transplantation in Patients with Newly Diagnosed Multiple Myeloma

Management of Primary Central Nervous System Lymphoma Using Intra-Arterial Chemotherapy With Osmotic Blood-Brain Barrier Disruption: Retrospective Analysis of the Sherbrooke Cohort

BackgroundPrimary central nervous system lymphomas (PCNSL) are rare and aggressive CNS tumors. Current management involves high-dose methotrexate (HD-MTX) typically administered intravenously (IV), despite the existence of the blood-brain barrier (BBB), which significantly decreases its bioavailability. Cerebral intra-arterial chemotherapy (CIAC) coupled with osmotic BBB disruption (OBBBD) can theoretically circumvent this issue.MethodsWe performed a retrospective analysis of patients with newly diagnosed PCNSL treated with HD-MTX-based CIAC+OBBBD at our center between November 1999 and May 2018. OBBBD was achieved using a 25% mannitol intra-arterial infusion. Patients were followed clinically and radiologically every month until death or remission. Demographics, clinical and outcome data were collected from the medical record. All imaging studies were reviewed for evidence of complication and outcome assessment. Kaplan-Meier analyses were used to compute remission, progression-free survival (PFS) as well as overall survival times. Subgroup analyses were performed using the log rank test.ResultsForty-four patients were included in the cohort. Median follow-up was 38 months. Complete response was achieved in 34 patients (79%) at a median of 7.3 months. Actuarial median survival and PFS were 45 months and 24 months, respectively. Age, ECOG and lesion location did not impact outcome. Complications included thrombocytopenia (39%), neutropenia (20%), anemia (5%), seizures (11%), stroke (2%), and others (20%).ConclusionCIAC using HD-MTX-based protocols with OBBBD is a safe and well-tolerated procedure for the management of PCNSL. Our data suggests better PFS and survival outcomes compared to IV protocols with less hematologic toxicity and good tolerability, especially in the elderly.

Skull Base Meningiomas in Patients with Neurofibromatosis Type 2: An International Multicenter Study Evaluating Stereotactic Radiosurgery.

Objective Meningiomas are the second most common tumors in neurofibromatosis type 2 (NF-2). Microsurgery is challenging in NF-2 patients presenting with skull base meningiomas due to the intrinsic risks and need for multiple interventions over time. We analyzed treatment outcomes and complications after primary Gamma Knife radiosurgery (GKRS) to delineate its role in the management of these tumors. Methods An international multicenter retrospective study approved by the International Radiosurgery Research Foundation was performed. NF-2 patients with at least one growing and/or symptomatic skull base meningioma and 6-month follow-up after primary GKRS were included. Clinical and radiosurgical parameters were recorded for analysis. Results In total, 22 NF-2 patients with 54 skull base meningiomas receiving GKRS as primary treatment met inclusion criteria. Median age at GKRS was 38 years (10-79 years). Most lesions were located in the posterior fossa (55.6%). Actuarial progression free survival (PFS) rates were 98.1% at 2 years and 90.0% at 5 and 10 years. The median follow-up time after initial GKRS was 5.0 years (0.6-25.5 years). Tumor volume at GKRS was a predictor of tumor control. Lesions >5.5 cc presented higher chances to progress after radiosurgery ( p = 0.043). Three patients (13.64%) developed adverse radiation effects. No malignant transformation or death due to meningioma or radiosurgery was reported. Conclusions GKRS is effective and safe in the management of skull base meningiomas in NF-2 patients. Tumor volume deserve greater relevance during clinical decision-making regarding the most appropriate time to treat. GKRS offers a minimally invasive approach of particular interest in this specific group of patients.

Radiation therapy with curative intention in men with de novo metastatic prostate carcinoma: shoot'em all!

About 5% of prostate cancer cases are metastatic at diagnoses. Radiotherapy of both primary tumor and secondary lesions can be, in addition to systemic treatments, a radical alternative for selected patients. Patients with de novo prostate carcinoma with bone or lymph node metastases were retrospectively reviewed. All patients received moderate hypofractionated IMRT/VMAT up to 63 Gy in 21 daily fractions of 3 Gy to prostate and metastases with neoadjuvant and concurrent androgen deprivation therapy (ADT). According to known advances some patients also received abiraterone, enzalutamide, or docetaxel. Between 2015-2020, we attended 26 prostate cancer patients (median age 69.5 years, range 52-84) with simultaneous oligometastases [mean 2.1 metastases, median 1.5 metastases (range 1-6)]. Eighteen patients (69%) presented lymph node metastases, 4 (15.5%) bone metastases and 4 (15.5%) both lymph node and bone metastases. With a median follow-up of 15.5 months (range 3-65 months), 16 patients (62%) are alive and tumor free while 10 (38%) are alive with tumor. Four patients (17%) developed tumor progression, out of irradiated area in all cases, with a median time to progression of 43.5 months (range 27-56 months). Actuarial progression-free survival (PFS) rates at 12 and 24 months were 94.1% and 84.7%, respectively. No grade > 2 acute or late complications were recorded. Simultaneous directed radical hypofractionated radiation therapy for prostate and metastases is feasible, well tolerated and achieves an acceptable PFS rate. However, further studies with longer follow-up are necessary to definitively address these observations.

Multicenter phase 2 trial of thalidomide in relapsed/refractory multiple myeloma: adverse prognostic impact of advanced age

AbstractRelapsed or refractory multiple myeloma has a poor outlook. Some patients respond to thalidomide; however, criteria for predicting response have not been conclusively identified. We initiated a prospective multicenter phase 2 trial in patients with relapsed/refractory myeloma using thalidomide up to the maximum dose, 800 mg/d. Interferon-α-2B (1.5-3.0 × 106 U, subcutaneously, 3 times per week) was added at week 12 if disease was responsive or stable. Patients intolerant of interferon continued thalidomide alone. Thalidomide with or without interferon was continued until disease progression. Objectives were to determine toxicity, response rate (RR), progression-free survival (PFS), and overall survival (OS) and to elucidate relevant prognostic factors. We enrolled 75 patients, with median age 64 years (range, 36-83 years). Median individual maximum-tolerated dose of thalidomide was 600 mg/d; 41% reached 800 mg/d. Overall RR was 28%, and 55% stable disease (SD). The only predictor for response was age 65 years or younger (38% versus 17%; P = .043). At 18 months median follow-up, the actuarial median PFS and OS were 5.5 and 14.6 months, respectively. Multivariate analysis for OS demonstrated age exceeding 65 years (median, 9.2 months versus longer than 26 months; P = .011), raised serum lactate dehydrogenase (P = .002), and raised serum creatinine (P = .007) predicted inferior outcomes. Nineteen patients received interferon. Ten discontinued owing to toxicity. Four of 12 patients who received interferon for longer than 4 weeks were converted from SD to partial response. Our findings confirm substantial activity of thalidomide in relapsed/refractory myeloma. Interferon may improve response in selected patients, but is often not tolerated. The inferior outcome demonstrated in those with the identified prognostic factors is important in planning management for such patients. (Blood. 2003;102:69-77)

Long-Term Outcomes of Allogeneic Hematopoietic Cell Transplantation in Patients with Newly Diagnosed Multiple Myeloma

Long-Term Outcomes of Allogeneic Hematopoietic Cell Transplantation in Patients with Newly Diagnosed Multiple Myeloma

Convexity Meningiomas in Patients with Neurofibromatosis Type 2: Long-Term Outcomes After Gamma Knife Radiosurgery

Convexity meningiomas are common tumors requiring treatment in patients with neurofibromatosis type 2 (NF2). Although different therapeutic options are described for sporadic convexity meningioma, much less is known about these lesions in patients with NF2 despite their distinct biology and need for multiple treatments. We analyzed the value of Gamma Knife radiosurgery (GKRS) as definitive treatment for convexity meningiomas in patients with NF2. This international multicenter retrospective study was approved by the International Radiosurgery Research Foundation. Patients with NF2 with at least 1 convexity meningioma and 6-month follow-up after primary GKRS were included. Inclusion criteria were met by 18 patients with NF2. A total of 120 convexity meningiomas (median treatment volume, 0.66 cm3 [range, 0.10-21.20 cm3]) were analyzed. Median follow-up after initial GKRS was 15.6 years (range, 0.6-25.5 years). Median age at GKRS was 32.5 years (range, 16-53 years). Median number of meningiomas per patient was 13 (range, 1-27), and median number of convexity lesions receiving GKRS per patient was 3.5 (range, 1-27). One case of tumor progression was reported 24 years after GKRS, leading to actuarial progression-free survival rates of 100% at 2, 5, and 10 years. No malignant transformation or death due to meningioma or radiosurgery was recorded. GKRS is safe and effective as definitive treatment of small to medium-sized convexity meningiomas in patients with NF2. Despite concerns about the particular mutational burden of these tumors, no malignant transformation manifested after treatment. GKRS represents a minimally invasive option that offers long-term tumor control to this specific group of patients.