Single-institute outcomes of palliative chemotherapy in metastatic head and neck squamous cell carcinoma (HNSCC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e18513-e18513
Author(s):  
Rujul H Parikh ◽  
Christopher W Fleming ◽  
Chandana A. Reddy ◽  
Shlomo A. Koyfman ◽  
Nikhil Joshi ◽  
...  
Keyword(s):  
Systemic Therapy ◽  
Palliative Chemotherapy ◽  
Statistical Significance ◽  
Treatment Options ◽  
Univariate Analysis ◽  
Progression Free Survival ◽  
Locoregional Failure ◽  
Distant Failure ◽  
Best Response ◽  
Organ Site

e18513 Background: Distantly metastatic HNSCC carries a poor prognosis with limited palliative systemic treatment options and a paucity of literature examining factors impacting outcomes of such therapy. We sought to evaluate characteristics conferring more favorable responses to frontline palliative systemic therapy after distant failure (DF). Methods: From an IRB-approved database, we identified 332 pts with metastatic HNSCC treated from 1999 to 2019. Pts with locoregional HNSCC who developed DF and subsequently were treated with palliative systemic therapy were included. Pts were categorized by disease factors, and outcomes were analyzed for progression-free survival (PFS) and overall survival (OS) with Kaplan-Meier curves and log-rank p-values. Results: A total of 85 pts were identified with median age 59.5 years (37-89); 82.4% male, 90.6% Caucasian, 52.9% with > 10 pack-years tobacco use history. Oropharynx primary was the most common site (36.5%) followed by oral cavity (23.5%). All 31 oropharynx cancer pts were HPV-related. Sixty-six pts initially received definitive chemoradiotherapy, with 43 receiving concurrent radiosensitizing cisplatin. Median time to DF was 15 months (m). Thirty pts (35.3%) had concurrent locoregional failure with DF. 62.4% had only one metastatic organ site, with lung-only metastasis in 43.5%. Carboplatin/paclitaxel was the most commonly used frontline palliative chemotherapy (50.6%); 22.4% received frontline nivolumab or pembrolizumab, and 9.4% were treated with frontline platinum/5-FU/cetuximab (9.4%). 63.5% of pts achieved a best response of stable disease or better with frontline therapy. At two years after initial DF, 6 pts (7%) were disease-free. Sixteen pts were alive at last follow-up. After DF, median PFS was 6.5 m and median OS was 10.6 m. On univariate analysis, HPV-related disease was associated with increased PFS (9.5 vs 5.1 m, p < 0.0001) and increased OS (21.1 vs 7.7 m, p < 0.0001). Pts with one metastatic organ site had better OS (11.0 vs 6.2 m, p = 0.047). There was a trend of increased OS with lung-only metastasis (14.4 vs 7.7 m, p = 0.0776), and absence of concurrent locoregional failure (10.8 vs 8.3 m, p = 0.1153). Conclusions: Our results demonstrate that HPV-related metastatic HNSCC is associated with a statistically significant increased PFS and OS. Additionally, there was a trend of increased OS with lower locoregional and distant metastatic burden at DF though statistical significance was not achieved.

A phase 1b multicenter study of trifluridine/tipiracil (FTD/TPI) in combination with irinotecan (IRI) in patients (pts) with metastatic or unresectable gastric and gastroesophageal adenocarcinoma (mGEC) after at least one line of treatment with a fluoropyrimidine and platinum (FP) containing regimen.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16006-e16006
Author(s):  
Farshid Dayyani ◽  
Kit Wah Tam ◽  
Edward Jae-Hoon Kim ◽  
Samuel Ejadi ◽  
Fa Chyi Lee ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Treatment Options ◽  
Progression Free Survival ◽  
Clinical Activity ◽  
Open Label ◽  
Meaningful Improvement ◽  
Best Response ◽  
Previously Treated ◽  
Phase 1B

e16006 Background: FTD/TPI, an antimetabolite, is approved for treatment of refractory mGEC. This study sought to determine whether the combination of FTD/TPI with IRI (“TASIRI”) was safe and effective in mGEC previously treated with FP. Methods: This investigator‐initiated, multicenter, open‐label, single-dose level, single‐arm phase 1b study enrolled pts with mGEC previously treated with at least one line of FP containing regimen. FTD/TPI was given at 25 mg/m2 twice daily on days 1 to 5 with 180 mg/m2 IRI on day 1 of a 14‐day cycle. The primary endpoint was progression-free survival at six months (mo) (PFS-6). The aim was to show an improvement of PFS-6 from 15% to at least 30% based on historical controls. Results: At the time of data-cutoff (03Feb2021), 23 pts were screened and ultimately 20 pts were treated. The study met its primary endpoint. With a median follow-up of 9.8 mo (range 0.7 – 17), 8 pts are still on treatment and 4 pts have died. PFS-6 is 53.9% (lower limit of 95% CI: 28%). Median PFS and overall survival are 6.9 mo and not reached, respectively. At the time of data-cutoff, data were available for 13 pts with measurable disease by RECIST criteria and at least 1 on-treatment scan. Of those, 11 had stable disease and 2 had progressive disease as best response (5 pts had tumor shrinkage < 30%), therefore the disease control rate was 84.6%. The most common any grade (G) treatment related adverse events (TRAE) were nausea (n = 14, 70%), diarrhea (n = 9, 45%), and fatigue (n = 8, 40%). G3-4 TRAE in > 5% of pts were anemia (17%) and neutropenia (9%). 2 serious TRAE were reported: G4 febrile neutropenia (n = 1) and G3 hypotension (n = 1). There was no G5 TRAE. Conclusions: The combination of TASIRI showed encouraging clinical activity with a meaningful improvement in PFS-6 compared to historic controls. TASIRI was well tolerated and no new safety signals were seen. TASIRI warrants further investigation for patients with refractory mGEC and limited treatment options. Updated results with longer follow-up will be presented at the meeting. Clinical trial information: NCT04074343.

Phase II study of the combination of thalidomide and irinotecan in patients with recurrent anaplastic gliomas not on enzyme inducing anticonvulsants

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 1564-1564 ◽  
Author(s):  
V. K. Puduvalli ◽  
P. Giglio ◽  
M. D. Groves ◽  
K. R. Hess ◽  
M. Gilbert ◽  
...  
Keyword(s):  
Treatment Options ◽  
Progression Free Survival ◽  
Antiangiogenic Agents ◽  
Synergistic Activity ◽  
Free Survival ◽  
Mr Perfusion Imaging ◽  
Kaplan Meier ◽  
Anaplastic Gliomas ◽  
Best Response ◽  
Grade 3

1564 Background: Patients with recurrent anaplastic glioma (AG) have few treatment options after initial alkylating agent therapy. In this study, the efficacy of thalidomide and irinotecan against recurrent AG was tested to assess if synergistic activity of cytotoxic and antiangiogenic agents could affect clinical outcome. Methods: Patients with recurrent AG with a KPS≥70 not on enzyme inducing anticonvulsants and with fewer than three relapses after radiation therapy and chemotherapies were eligible; the total planned enrollment is 39 patients. Irinotecan is administered at 125 mg/m2 weekly for 4 weeks followed by 2 weeks rest; thalidomide is initiated at 100 mg daily and escalated weekly up to 400 mg daily. Warfarin (1 mg) is given for prevention of venous thromboembolism (VTE). Patients undergo clinical and radiologic evaluations every 6-weeks. The primary endpoint is progression free survival at 6 months (PFS-6). To determine possible radiologic correlates to treatment effects, DCE- MR perfusion-imaging studies are obtained at baseline and subsequent follow up visits. Results: 17 are evaluable for response; the remainder were inevaluable. All evaluable patients had previously failed temozolomide and 9 had also failed nitrosourea therapy. The median age is 44 yrs and median KPS is 90. Four patients are alive and progression free at 6-months whereas 9 have progressed; the median progression free survival is 23 weeks and the PFS-6 is 34%. The best response was a CR in one patient, PR in 2 and stable disease in 9. Two patients have died of unspecified causes probably related to treatment. Median overall survival has not been reached; the 12-month and 18 month survivals by Kaplan Meier analysis are 73% and 26% respectively. Grade 3 and 4 toxicities included fatigue (29%), leukopenia (29%), nausea/vomitting (24%), and diarrhea (18%) requiring dose reductions. Two patients had VTE. Conclusions: The preliminary results of this ongoing study suggest that the combination of irinotecan and thalidomide has activity in patients with recurrent anaplastic gliomas; the ongoing assessment of this combination in patients with AG will more definitively define whether the combination can be an effective second line therapy for this population. [Table: see text]

scholarly journals Treatment Patterns and Outcomes Among Elderly Glioblastoma Patients at KFMC, Riyadh.

2021 ◽  
Author(s):  
Amal Maire ◽  
Ahmed M. Maklad ◽  
Abdullah Altwairqi ◽  
Wafaa AlShakweer ◽  
Mohamed Senosi ◽  
...  
Keyword(s):  
Adjuvant Treatment ◽  
Performance Status ◽  
Treatment Options ◽  
Univariate Analysis ◽  
Eastern Cooperative Oncology Group ◽  
Progression Free Survival ◽  
Treatment Patterns ◽  
Subtotal Resection ◽  
Ecog Performance Status ◽  
Significant Factors

Abstract IntroductionManagement of elderly patients with cancer is a controversial scenario and needs careful assessment and selection for aggressive radical treatment and chemotherapy protocols versus short-course radiotherapy without chemotherapy. Of note, definitions of the elderly vary in the glioblastoma (GBM) literature, with most of the randomized trials including patients aged 60, 65, or 70 years or older.Aim of the workTo evaluate treatment patterns and outcome among elderly GBM patients treated in KFMC, Riyadh. The primary endpoint is overall survival (OS) and the Secondary endpoint is progression-free survival (PFS) in relation to different treatment options and prognostic factors. MethodsThis is a retrospective study, included elderly GBM patients treated at KFMC, Riyadh, KSA between 1/2008 till 1/2018. 59 patients diagnosed with GBM ≥ 60 years were reviewed regarding radiotherapy (Rth) fractionation modalities, surgery, and chemotherapy (CTR) given in correlation to PFS, OS.Results59 patients were recruited in our study with median age 66 range (60-81) years, 47 (80%) were males. 37 patients (62.7%) had Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥2, and 22 patients (37.3%) had PS < 2. Gross total resection (GTR) and subtotal resection (STR) was done in 49 (82.9%) patients, and the median follow-up was 12 months.38 (64%) patients received conventional Rth 60 Gray (Gy)/30 fractions or equal doses and 21 (36%) patients received hypofractionation Rth (40 Gy/15, 25 Gy/5 or 30 Gy/10 fractions).The median OS was 12 months (95% CI,9.52-14.48). For univariate analysis, receiving a conventional Rth and completion of 6 months adjuvant CTR were significant factors for O.S (P= 0.043 and 0.026) respectively. For multivariate those were also significant (P=0.035 and 0.002) respectively.The median PFS was 9 months (95% CI, 6.13-11.87). For univariate analysis PS, time to start adjuvant treatment, and completion of 6 months CTR were significant factors for PFS. For multivariate analysis starting adjuvant treatment within 2 months and completed CTR 6 months were significant factors (P=0.032 and 0.04) respectively. ConclusionElderly GBM patients who received conventional Rth and completed adjuvant 6 months CTR achieved a better OS, while starting adjuvant treatment earlier than 2 months and completed adjuvant CTR 6 months were associated with a better PFS, further prospective studies are needed to confirm our finding.

Resting palliative chemotherapy in patients with gastric cancer.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 122-122
Author(s):  
Hee Yeon Lee ◽  
Young Seon Hong ◽  
Hae Myung Jeon ◽  
Cho Hyun Park ◽  
Kyo Young Song ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Progressive Disease ◽  
Palliative Chemotherapy ◽  
Recurrent Disease ◽  
Progression Free Survival ◽  
Complete Response ◽  
Palliative Surgery ◽  
Free Survival ◽  
Best Response ◽  
Palliative Setting

122 Background: In gastric cancer, platinum and fluorouracil combination chemotherapy (CTx) is commonly used. But the optimal duration of CTx in palliative setting is not known. Thus, we reviewed the pts who rested CTx despite of persistent disease control. Methods: From Mar 2007 to Feb 2012 at Seoul St. Mary’s hospital, we retrospectively reviewed pts as follows; (1) had metastatic or recurrent gastric cancer, (2) received 9 cycles of FOLFOX as 1st-line, (3) had no progressive disease (PD) and rested after completion of 9th cycle. Results: Total 25 pts were reviewed. Median age was 54 (36~77) and 15 pts (60%) were male. 13 pts (52%) had recurrent disease and 12 metastatic initially. All pts were treated with oxaliplatin 100 mg/m2, leucovorin 400 mg/m2 on day 1 and 5-FU 1200 mg/m2 on day 1-2 every 2 weeks. All pts had metastasis; carcinomatosis peritonei (CP, 56%), lymph node (36%), liver (20%) and bone (8%). Nine pts (48%) had non-measurable lesions and 3 no evidence of disease (NED) on CT after palliative surgery. Response evaluation was done every 3 cycles. Among 22 pts with evaluable disease, 5 (20%) showed complete response (CR), 8 (32%) partial response (PR), 2 (8%) stable disease (SD) and 7 (28%) non-CR/non-PD as best response. Median progression free survival (PFS) was 14.2 m (95% CI, 6.6-21.9). The PFS in CP vs. non-CP was 9.9 vs. 21.5 m (log rank P = .037). And PFS according to best response were as follows; 25.5 m in CR + NED group, 15.7 PR, 13.4 non-CR/non-PD and 4.3 SD (log rank P = .014). Other factors did not seem to affect PFS. Conclusions: This study suggested that resting CTx in selected pts would be reasonable in gastric cancer. Especially the presence of CP and the grade of response seemed to be important in patient selection.

NRAS mutation: A potential biomarker of clinical response to immune-based therapies in metastatic melanoma (MM).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 9019-9019 ◽  
Author(s):  
Douglas Buckner Johnson ◽  
Christine Marie Lovly ◽  
Marisa Flavin ◽  
Gregory Dan Ayers ◽  
Zhiguo Zhao ◽  
...  
Keyword(s):  
Clinical Benefit ◽  
Statistical Significance ◽  
Progression Free Survival ◽  
Nras Mutation ◽  
Mutation Status ◽  
Best Response ◽  
Primary Endpoints ◽  
Potential Biomarker ◽  
Genetic Subtype ◽  
Secondary Endpoints

9019 Background: NRAS mutant (mut) MM comprises a distinct, molecularly defined cohort of this disease that appears to have a poor prognosis compared to other genetic subsets. In contrast to BRAF mut MM, there are no effective small molecule inhibitors specifically targeting NRAS. Immune based therapy (IT) has become a mainstay in MM treatment, especially in BRAF wild type (WT) patients (pts). Biomarkers to predict which pts will benefit from IT have not been validated. The goal of this study was to evaluate whether genetic subtype (specifically NRAS) has a role in predicting benefit from IT in BRAF WT MM. Methods: We identified 173 pts from 3 institutions who underwent clinical genotyping (exome or PCR based) for NRAS and BRAF mutation from 1/09 – 8/12 and were treated with IT (defined as IL-2, ipilimumab (ipi), or anti-PD-1 (nivolumab, MK3475)/ PD-L1 (MPDL3280A)). Only BRAF WT pts were included. Primary endpoints were response rate (RR) and clinical benefit rate (CBR), defined as RR + stable disease lasting >24 wks to IT (best response as assessed by treating clinicians in any line of IT). Secondary endpoints were overall survival (OS) and progression-free survival (PFS) from first line IT. Results: Of the 173 pts, 59 had NRAS mut MM compared to 114 WT/WT (no mutation in NRAS or BRAF). Improved clinical outcomes were seen in the NRAS mut compared to WT/WT cohort in terms of RR (32% vs. 18%, p=0.042), and CBR (49% vs. 30%, p=0.012). Improvements in PFS and OS did not reach statistical significance. By specific IT, NRAS mutation predicted benefit compared to WT/WT for anti-PD-1/PD-L1 (RR 78% vs. 19%, p=0.002; CBR 78% vs. 29%, p=0.013, n=30) and ipi (RR 18% vs. 12%, p=0.315; CBR 41% vs. 22%, p=0.018, n=137). No significant differences were observed with IL-2 (RR 33% vs. 28%, p=0.730; CBR 33% vs. 39%, p=0.741, n=33). Conclusions: This study demonstrates that pts with NRAS mut MM achieve increased clinical benefit from IT compared to pts with BRAF/NRAS WT MM. A larger, prospective analysis is necessary to validate and expand on these results, including those with BRAF mut and KIT mut MM. However, our data suggest that NRAS mutation status may be a biomarker of response to IT in MM and that molecularly targeted immunotherapy may be feasible.

Updated results of single-agent ibrutinib in recurrent/refractory primary (PCNSL) and secondary CNS lymphoma (SCNSL).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 7515-7515 ◽  
Author(s):  
Christian Grommes ◽  
Igor T. Gavrilovic ◽  
Thomas Joseph Kaley ◽  
Craig Nolan ◽  
Antonio Marcilio Padula Omuro ◽  
...  
Keyword(s):  
Adverse Events ◽  
Drug Treatment ◽  
Clinical Response ◽  
Systemic Disease ◽  
Treatment Options ◽  
Single Agent ◽  
Progression Free Survival ◽  
Primary Brain Tumor ◽  
Cns Lymphoma ◽  
Best Response

7515 Background: PCNSL is an aggressive primary brain tumor with median progression free survival (PFS) after upfront methotrexate-based chemotherapy of 2-3 years. Outcome and treatment options are poor for recurrent/refractory (r/r) disease. Ibrutinib has shown promising clinical response in Mantle cell lymphoma, CLL, Marginal Zone, and Waldenström. This trial investigates Ibrutinib in patients with r/r PCNSL and SCNSL. Methods: Eligible patients had r/r PCNSL or SCNSL, age≥18, ECOG≤2, normal end-organ function, and unrestricted number of CNS directed prior therapies. In patients with SCNSL disease, systemic disease needed to be absent. Results: Twenty-five patients were enrolled (3 at 560 mg; 22 at 840 mg). Median age was 68 (range 21-85); 15 were women. Median ECOG was 1 (0: 2, 1: 15, 2: 8). 64% had PCNSL and 36% SCNSL; 68% had recurrent disease. Seventeen had parenchymal disease, 3 isolated cerebrospinal fluid (CSF) involvement and 5 both. Seven grade 4 adverse events were observed in 7 patients neutropenia (in 3 patients), lymphopenia (2), sepsis (1), and ALT elevation (1). Fourteen patients developed 20 grade 3 toxicities, including lymphopenia in 5 patients, hyperglycemia in 3, ALT elevation in 2, thrombocytopenia in 2, lung infection in 2, AST elevation in 1, neutropenia in 1, urinary tract infection in 1, colitis in 1, febrile neutropenia in 1 and fungal encephalitis in 1. The most common toxicities at any grade were hyperglycemia, thrombocytopenia and anemia of which most were grade 1/2. No grade 5 events have been observed. After a median follow-up of 414 days (range 289-674), 22/25 patients were evaluated for response (3 did not complete at least 15 days of drug treatment). Over all response was 68% (17/22; 77% (17/22) in patient that completed at least 15 days of drug treatment) with 10 CR, 7 PR, 2 SD and 3 PD as best response. The median PFS is 4.6 months (5.4 months in patients that completed at least 15 days of drug treatment; longest: 15.3 months). The median overall survival has not been reached. Conclusions: Patients with CNS lymphoma tolerate Ibrutinib with manageable adverse events. Clinical response was seen in 68% of CNS lymphoma patients. Clinical trial information: NCT02315326.

scholarly journals Eribulin Efficacy on Brain Metastases in Heavily Pretreated Patients with Metastatic Breast Cancer

2021 ◽  
Vol 10 (6) ◽  
pp. 1272
Author(s):  
Renaud Sabatier ◽  
Johan Martin ◽  
Cécile Vicier ◽  
Mathilde Guérin ◽  
Audrey Monneur ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastases ◽  
Hormone Receptors ◽  
Molecular Subtype ◽  
Treatment Options ◽  
Univariate Analysis ◽  
Evaluation Criteria ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Free Survival

The onset of brain metastases (BM) is a major turning point during advanced breast cancer (ABC) evolution, with only few treatment options when local therapies have failed. The therapeutic effect of eribulin, a wildly used drug in the treatment of ABC, remains unclear in this setting. Patients and Methods: We performed a retrospective observational study to assess eribulin efficacy in patients with ABC who displayed BM at time of eribulin initiation. We collected data from the medical files of all ABC patients who received eribulin at our institution from 2012 until 2020. Our main endpoint was the central nervous system (CNS) progression-free survival. (CNS-PFS). Other evaluation criteria were extra-cranial progression free survival (PFS) and overall survival (OS). Results: Twenty patients with BM monitoring data available were selected out of the 549 who received eribulin during the inclusion period. Fifteen patients (75%) had BM progressive as the best response, three patients (15%) had disease stabilization for more than 6 months and only one patient had a partial response according to RECIST 1.1 criteria. Median CNS-PFS was 3.39 months (95CI (3.02–3.76)). Cox univariate analysis identified molecular subtype as the only prognostic parameter in our cohort, with patients with hormone-receptor positive tumors less likely to experience CNS progression than those with triple-negative MBC (HR = 0.23 (95CI = 0.07–0.80), p = 0.021). Median extra-cranial PFS was 2.67 months (95CI (2.33–3.01)). Median OS was 7.68 months (95CI (0–17.41)). Conclusion: Eribulin seems to have only a limited impact on BM evolution. Hormone receptors expression may identify a subset of patients with better BM control.

scholarly journals Phase Ib of Copanlisib in Combination with Ibrutinib in Recurrent/Refractory Primary CNS Lymphoma (PCNSL)

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1598-1598 ◽  
Author(s):  
Christian Grommes ◽  
Igor Gavrilovic ◽  
Alexandra M Miller ◽  
Jacqueline B Stone ◽  
Thomas Kaley ◽  
...  
Keyword(s):  
Adverse Events ◽  
Treatment Options ◽  
Single Agent ◽  
Primary Cns Lymphoma ◽  
Progression Free Survival ◽  
Primary Brain Tumor ◽  
Antimicrobial Treatment ◽  
Pi3k Inhibitor ◽  
Cns Lymphoma ◽  
Best Response

BACKGROUND: PCNSL is an aggressive primary brain tumor with median progression free survival (PFS) after upfront methotrexate-based chemotherapy of 2-3 years. Outcome and treatment options are poor for recurrent/refractory (r/r) disease. This trial combines the pan-PI3K inhibitor copanlisib with Ibrutinib in patients with r/r PCNSL. METHODS: Eligible patients had r/r PCNSL, age≥18, ECOG≤2, normal end-organ function, and an unrestricted number of CNS directed prior therapies. Ibrutinib was given orally daily; copanlisib intravenously on days 1, 8, and 15 of each 28-day cycle. RESULTS: Six patients have been enrolled so far and received copanlisib at 60 mg and ibrutinib at 560 mg. Median age was 68 (range 50-77); 3 were women. Median ECOG was 1 (0: 2, 1: 3, 2: 1). All had recurrent parenchymal disease. Three had additional cerebrospinal fluid (CSF) involvement. Two had received prior single-agent ibrutinib. Initially, no prophylactic antimicrobial treatment was required. PCP prophylaxis was made mandatory after one patient developed PCP pneumonia leading to a grade 5 lung infection. Four patients are still on trial and one withdrew due to personal choice. Two grade 4 adverse events were observed in 2 patients (LFT elevation, lymphopenia); four grade 3 events in 3 patients (rash, lymphopenia, LFT elevation). The most common toxicities at any grade were transient, infusion-related hyperglycemia and hypertension. No Aspergillus infections have been observed. Enrollment into the next dose level (copanlisib 60 mg, ibrutinib 840 mg) is ongoing. After a median follow-up of 180 days (range 46-249), all patients were evaluated for response with an overall response rate of 67% with 1 CR, 3 PR, 1 SD and 1 PD as best response. CONCLUSION: Treatment with copanlisib and ibrutinib in patients with PCNSL has manageable adverse events after initiation of mandatory PCP prophylaxis. Clinical response was seen in 67% of patients. Disclosures Grommes: Squipps: Speakers Bureau; Kite: Consultancy; BTG: Consultancy. OffLabel Disclosure: The combination of the BTK inhibitor ibrutinib and the pan PI3K inhibitor copanlisib in recurrent PCNSL will be discussed

Extent of tumor removal and molecular markers in cerebral glioblastoma: a combined prognostic factors study in a surgical series of 105 patients

2012 ◽  
Vol 117 (2) ◽  
pp. 204-211 ◽  
Author(s):  
Maurizio Salvati ◽  
Angelo Pichierri ◽  
Manolo Piccirilli ◽  
Giacoma Maria Floriana Brunetto ◽  
Alessandro D'Elia ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Statistical Power ◽  
Statistical Significance ◽  
Univariate Analysis ◽  
Methylation Status ◽  
Progression Free Survival ◽  
Rank Test ◽  
Survival Prediction ◽  
Surgical Removal ◽  
Total Removal

Object In this paper, the authors' goal was to evaluate the prognostic value of YKL-40 expression as a prognostic factor for glioblastomas and to compare its validity to the already known MGMT. Methods Between January 2002 and January 2007, 105 patients were treated for cerebral glioblastoma. The extent of removal was classified in 4 groups. YKL-40 expression was evaluated by a semiquantitative immunohistochemical staining scale (0, no staining; 1, mild expression; and 2, strong expression). MGMT promoter methylation status was analyzed with methylation-specific polymerase chain reaction. All patients received adjuvant radiotherapy and chemotherapy. Kaplan-Meier curves were used to analyze progression-free survival (PFS) and overall survival (OS), and to compare these parameters between the subgroups stratified by extent of surgical removal, MGMT methylation, and YKL-40 expression. The log-rank test was used to determine statistical significance. A multivariate regression analysis was applied to extent of removal, YKL-40 expression, and MGMT status to check their specific statistical power and to test the independence of the variables. Results There were 55 men and 50 women with a mean age of 58 years. Extent of surgical removal is reported. The MGMT promoter was methylated in 48 patients and nonmethylated in 57. Analysis of YKL-40 expression is reported. The median PFS was 10.7 months (14.9 months in the gross-total removal subgroup) (p < 0.0001), and the median OS was 12.5 months (17.4 months in the gross-total removal group) (p < 0.0001). In the univariate analysis, OS was significantly correlated to the extent of resection (p < 0.0001), MGMT status (p < 0.0001), and YKL-40 (p < 0.0001). Multivariate analysis showed that all 3 factors reached statistical significance with respect to patient survival. In particular, surgical removal contributed more than the 2 other factors to the survival prediction (β = −0.6254). Interestingly, YKL-40 (β = −0.3867) contributed more than MGMT (β = −0.1705) to the predicted survival. Conclusions The extent of removal is the most important factor influencing the OS of patients harboring glioblastomas. When biological aggressiveness is taken into account, YKL-40 expression was found to be an independent prognostic factor that predicts OS better than MGMT status.

Systemic Therapy for Hepatocellular Carcinoma: Advances and Hopes

2020 ◽  
Vol 20 (2) ◽  
pp. 84-99
Author(s):  
Chen-Hao Zhang ◽  
Ming Li ◽  
You-Pei Lin ◽  
Qiang Gao
Keyword(s):  
Hepatocellular Carcinoma ◽  
Systemic Therapy ◽  
Checkpoint Inhibitors ◽  
Statistical Significance ◽  
Progression Free Survival ◽  
Second Line ◽  
Future Directions ◽  
Free Survival ◽  
First Line Therapy ◽  
Systemic Treatments

The majority of patients with hepatocellular carcinoma (HCC) are diagnosed at an advanced stage that can only benefit from systemic treatments. Although HCC is highly treatmentresistant, significant achievements have been made in the molecular targeted therapy and immunotherapy of HCC. In addition to regorafenib, cabozantinib and ramucirumab were approved for the second- line targeted treatment by the FDA after disease progression on sorafenib. Nivolumab failed to demonstrate remarkable benefit in overall survival (OS) as first-line therapy, while pembrolizumab did not achieve pre-specified statistical significance in both OS and progression-free survival (PFS) as second-line treatment. Combinations of targeted agents, immune checkpoint inhibitors and other interventions showed favorable results. In this review, we summarized the progress of systemic therapy in HCC and discussed the future directions of the treatment of HCC.

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