scholarly journals The use of immunotherapy treatment in malignant pheochromocytomas/paragangliomas: a case report

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Robin Raquel Rodriguez ◽  
Saleha Rizwan ◽  
Khaled Alhamad ◽  
Gene Grant Finley
Keyword(s):  
Clinical Trials ◽  
Radiation Therapy ◽  
Case Report ◽  
Neural Crest Cell ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Chemotherapeutic Agents ◽  
Current Standard ◽  
Off Label ◽  
Current Standard Treatment

Abstract Background Pheochromocytomas are a subset of paragangliomas, which are a rare group of neural crest cell-derived tumors. Malignant cases of both pheochromocytomas and paragangliomas are even rarer, and currently there is no standard of care. This case report details the use of off-label immunotherapy and its efficacy in the management of the aforementioned tumor. Case presentation Herein is presented a case of a 60-year-old Caucasian female with a rare malignant pheochromocytoma. The tumor was determined to be unresectable because of involvement of surrounding organs. Radiation therapy was also not a viable option because of concerns over appreciable toxicity in relation to mass size. As there is no standard of care for malignant cases, the patient was started on chemotherapeutic agents but was soon shown to be intolerant to this treatment. As she was ineligible for several clinical trials, the patient was started on the off-label immunotherapeutic agents nivolumab and ipilimumab. Immunotherapy use resulted in decreased tumor size, improved quality of life, and reconsideration for radiation therapy. Conclusions The use of immunotherapy in pheochromocytoma in this patient clearly demonstrated substantial benefit, as she was able to be reconsidered for radiation therapy. Not only has the patient been tolerant of this treatment, but she has exhibited progression-free survival of over 20 months. As there is no current standard treatment for malignant pheochromocytomas, the success of its use in this patient lends support to the ongoing clinical trials regarding the use of immunotherapy in rare tumors, including pheochromocytomas.

scholarly journals Co-Clinical Trials: An Innovative Drug Development Platform for Cholangiocarcinoma

2021 ◽  
Vol 14 (1) ◽  
pp. 51
Author(s):  
Brinda Balasubramanian ◽  
Simran Venkatraman ◽  
Kyaw Zwar Myint ◽  
Tavan Janvilisri ◽  
Kanokpan Wongprasert ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Targeted Therapy ◽  
Drug Development ◽  
Surgical Resection ◽  
Treatment Options ◽  
Standard Of Care ◽  
Time Data ◽  
Current Standard ◽  
Innovative Drug ◽  
Curative Intent

Cholangiocarcinoma (CCA), a group of malignancies that originate from the biliary tract, is associated with a high mortality rate and a concerning increase in worldwide incidence. In Thailand, where the incidence of CCA is the highest, the socioeconomic burden is severe. Yet, treatment options are limited, with surgical resection being the only form of treatment with curative intent. The current standard-of-care remains adjuvant and palliative chemotherapy which is ineffective in most patients. The overall survival rate is dismal, even after surgical resection and the tumor heterogeneity further complicates treatment. Together, this makes CCA a significant burden in Southeast Asia. For effective management of CCA, treatment must be tailored to each patient, individually, for which an assortment of targeted therapies must be available. Despite the increasing numbers of clinical studies in CCA, targeted therapy drugs rarely get approved for clinical use. In this review, we discuss the shortcomings of the conventional clinical trial process and propose the implementation of a novel concept, co-clinical trials to expedite drug development for CCA patients. In co-clinical trials, the preclinical studies and clinical trials are conducted simultaneously, thus enabling real-time data integration to accurately stratify and customize treatment for patients, individually. Hence, co-clinical trials are expected to improve the outcomes of clinical trials and consequently, encourage the approval of targeted therapy drugs. The increased availability of targeted therapy drugs for treatment is expected to facilitate the application of precision medicine in CCA.

scholarly journals De-Escalation of Therapy for Patients with Early-Stage Squamous Cell Carcinoma of the Anus

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2099
Author(s):  
Eric Miller ◽  
Jose Bazan
Keyword(s):  
Squamous Cell Carcinoma ◽  
Radiation Therapy ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Early Stage ◽  
Intensity Modulated Radiation Therapy ◽  
Late Toxicity ◽  
Standard Of Care ◽  
The Elderly ◽  
Current Standard

The incidence of squamous cell carcinoma of the anus (SCCA) is increasing, particularly in the elderly, with increased mortality in this age group. While the current standard of care for localized SCCA remains chemoradiation (CRT), completion of this treatment can be challenging with risks for severe acute and late toxicity. It remains unclear if full course CRT is required for the management of early-stage SCCA or if de-escalation of treatment is possible without compromising patient outcomes. Alternative therapies include radiation therapy alone or local excision for appropriate patients. Modifying standard CRT may also reduce toxicity including the routine use of intensity-modulated radiation therapy for treatment delivery, modification of treatment volumes, and selection and dosing of concurrent systemic therapy agents. Finally, we provide an overview of currently accruing prospective trials focused on defining the role of de-escalation of therapy in patients with early-stage SCCA.

P14.90 Survival outcomes and prognostic factors in glioblastoma patients treated with radiotherapy plus concomitant and adjuvant temozolomide - real-world study

2021 ◽  
Vol 23 (Supplement_2) ◽  
pp. ii55-ii55
Author(s):  
M J Sousa ◽  
J Magalhães ◽  
R Basto ◽  
C Costa ◽  
A Pego ◽  
...  
Keyword(s):  
Survival Rate ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Rank Test ◽  
Survival Outcomes ◽  
Hematologic Toxicity ◽  
Current Standard ◽  
Adjuvant Temozolomide ◽  
Standard Of Care Treatment ◽  
Ecog Ps

Abstract BACKGROUND Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumour in adults. The current standard of care for newly diagnosed GBM is maximal surgical resection, followed by radiotherapy plus concomitant and adjuvant temozolomide (TMZ). This study aimed to evaluate the survival outcomes and identify predictors of survival among these patients. MATERIAL AND METHODS We performed a single-centre retrospective analysis of GBM patients treated with radiotherapy plus concomitant and adjuvant TMZ from 2013 to 2020. The analyses of progression-free survival (PFS) and overall survival (OS), each one evaluated starting from initial diagnosis, were performed. Survival curves were estimated with the Kaplan- Meier method and compared using the log-rank test. RESULTS Fifty-eight patients were identified. The median age was 61 years (range 18- 80), 51 (88%) patients were in ECOG-PS 0–1, 6 (10%) patients had isocitrate dehydrogenase (IDH) mutation and 53 (91%) of patients had undergone debulking surgery. At a median follow-up of 21 months, median OS was 12.8 months (95% confidence interval [CI] 9.7–15.9), whereas median PFS was 9.5 months (95% CI 8.5–10.5). The 1-year survival rate was 42% and the 2-year survival rate was 10%. Grade 3 or 4 hematologic toxicity occurred in 11 (19%) patients. Twenty-five (42%) patients completed at least 6 cycles of TMZ monotherapy with statistically significant differences between this sub-group and those who weren’t able to continue TMZ monotherapy [median OS 19.3 months (95% CI 14.4–24.2) vs 10.6 months (95% CI 7.8–13.4) p<0.001]. ECOG-PS = 0 [median OS 16.7 months (95% CI 13.4–20.0, p=0.001)] and patients under 65 years of age [median OS 15.6 months (95% CI 12.3–18.9, p=0.02) were associated with significantly better median OS. CONCLUSION The current standard of care treatment for GBM remains poor. An important factor predictor of survival is the completion of the 6 maintenance cycles of TMZ. At baseline, ECOG PS and the patient’s age could be used to define patient prognosis.

EXTH-56. ZIKA VIRUS TREATMENT SIGNIFICANTLY PROLONGS SURVIVAL IN A GLIOBLASTOMA PATIENT DERIVED XENOGRAFT MODEL

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi175-vi176
Author(s):  
Parvez Akhtar ◽  
Samuel Zwernik ◽  
Deborah Donohoe ◽  
Catherine Warner ◽  
Dmitry Bosenko ◽  
...  
Keyword(s):  
Median Survival ◽  
Zika Virus ◽  
Oncolytic Virus ◽  
Xenograft Model ◽  
Standard Of Care ◽  
Control Group ◽  
Current Standard ◽  
Patient Derived Xenograft ◽  
Current Standard Treatment ◽  
Tumor Remission

Abstract The poor median survival for patients with glioblastoma (GBM) of 15 months has not budged for the past 15 years, when the current standard treatment was first approved. There is no standard of care chemotherapy for recurrent GBM. We previously showed that Zika virus (ZIKV) tropism for GBM cells is mediated through the receptor tyrosine kinase, AXL. This infection is cytotoxic. In this study we show that ZIKV is an effective oncolytic virus in a patient derived xenograft model. Fox N1 Nude homozygous female mice 6-8-weeks-old were grouped into 4 experimental arms: two patient derived cell lines, each with a ZIKV treated and a control group. There were 12 mice in each arm. Animals received subcutaneous flank injections of GBM 8049 or its AXL CRISPR knockout 8049 AXLKO (2x106 cells). When tumors reached 200 mm3, mice received intra-tumoral injection of 2.5x106 ZIKV particles or saline. ZIKV induced complete tumor remission in 22 of 24 animals (8049: 11/12; 8049 AXLKO: 11/12). There was no tumor remission in the saline treated animals. Median survival of 8049 and 8049 AXLKO ZIKV treated mice was 124 days and 125 days, respectively. This is compared to median survival of control animals 8049: 42 days; 8049 AXLKO: 46 days (P= 0.001). Among ZIKV treated mice, there were two recurrences: one in the 8049 tumor (24 days after significant tumor remission) and one 8049 AXLKO tumor (7 days after significant tumor remission). We conclude that ZIKV should be considered a candidate oncolytic virus for GBM.

scholarly journals Intestinal perforation after radical cystectomy due to drain: Case report

2014 ◽  
Vol 86 (4) ◽  
pp. 295
Author(s):  
Salih Budak ◽  
Hüseyin Aydemir ◽  
Hasan Salih Saglam ◽  
Oztug Adsan
Keyword(s):  
Bladder Cancer ◽  
Case Report ◽  
Radical Cystectomy ◽  
Urinary Diversion ◽  
Potential Risk ◽  
Intestinal Perforation ◽  
Standard Treatment ◽  
Foley Catheter ◽  
Current Standard ◽  
Current Standard Treatment

The current standard treatment for nonmetastatic invasive bladder cancer is radical cystectomy with urinary diversion. Radical cystectomy surgery carries a serious potential risk of complications. In this case report, an intestinal perforation which was thought to be occurred due to a Foley catheter placed as a drain after the cystectomy is presented.

Network meta-analysis (NMA) of immuno-oncology (IO) monotherapy as first-line (1L) treatments (txs) for advanced non-small cell lung cancer (NSCLC) with PD-L1 expression ≥50%.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21091-e21091
Author(s):  
Nicholas Freemantle ◽  
Yingxin Xu ◽  
Florence Wilson ◽  
Patricia Guyot ◽  
Chieh-I Chen ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Meta Analysis ◽  
Objective Response ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Sensitivity Analyses ◽  
Current Standard ◽  
Feasibility Assessment ◽  
Hazard Ratios ◽  
Nsclc Patients

e21091 Background: For advanced NSCLC patients (pts) with high (≥50%) PD-L1 expression, effective IO mono options with survival benefits are approved (pembrolizumab mono, current standard of care) and emerging (cemiplimab). In a recent Phase 3 trial, cemiplimab, a high-affinity, highly potent human PD-1 inhibitor approved for tx of advanced cutaneous squamous cell carcinoma, demonstrated significantly improved overall survival (OS) and progression-free survival (PFS) vs chemotherapy (CT) in advanced NSCLC pts with PD-L1 ≥50%. A systematic literature review and NMA were conducted to identify/compare the efficacy/safety from randomized controlled trials (RCTs) for cemiplimab vs pembrolizumab or other IO mono published 2010–19. Methods: Relevant RCTs were identified by searching Embase, MEDLINE, Cochrane, and conference proceedings with predefined search strategies according to ISPOR, NICE, and PRISMA guidelines. An NMA with time-varying hazard ratios (HRs) was performed for OS and PFS. Analyses were conducted for objective response rate (ORR), Grade (G) 3–5 all-cause adverse events (AE), G3–5 immune-mediated AE (IMAE) and discontinuation due to AEs (DAE). Fixed-effect models were used due to limited evidence. Results with standard constant HRs and various sensitivity analyses were conducted to account for differences in RCT designs and other txs. Results: The feasibility assessment determined that EMPOWER-Lung 1, KEYNOTE-024, and KEYNOTE-042 trials were eligible. IMpower110 was excluded since an incompatible PD-L1 assay (SP142) was used for pt selection. For 1L advanced NSCLC with PD-L1 ≥50%, cemiplimab was associated with significantly greater PFS and ORR, and comparable OS, G3–5 AEs, IMAEs, and all-cause DAEs vs pembrolizumab (Table). At 2 yrs, numerically more pts receiving cemiplimab vs pembrolizumab were alive (59% vs 49%) and significantly more were alive w/o progression (37% vs 18%). Conclusions: In advanced NSCLC pts with PD-L1 ≥50%, cemiplimab mono demonstrated significant improvements in PFS and ORR, and comparable OS, safety/tolerability vs pembrolizumab.[Table: see text]

scholarly journals CURATE.AI: Optimizing Personalized Medicine with Artificial Intelligence

2019 ◽  
Vol 25 (2) ◽  
pp. 95-105
Author(s):  
Agata Blasiak ◽  
Jeffrey Khong ◽  
Theodore Kee
Keyword(s):  
Clinical Trials ◽  
Personalized Medicine ◽  
Standard Of Care ◽  
Small Data ◽  
Current Standard ◽  
Dose Selection ◽  
Support Tool ◽  
Combination Treatments ◽  
Multiple Challenges ◽  
Over Time

The clinical team attending to a patient upon a diagnosis is faced with two main questions: what treatment, and at what dose? Clinical trials’ results provide the basis for guidance and support for official protocols that clinicians use to base their decisions upon. However, individuals rarely demonstrate the reported response from relevant clinical trials, often the average from a group representing a population or subpopulation. The decision complexity increases with combination treatments where drugs administered together can interact with each other, which is often the case. Additionally, the individual’s response to the treatment varies over time with the changes in his or her condition, whether via the indication or physiology. In practice, the drug and the dose selection depend greatly on the medical protocol of the healthcare provider and the medical team’s experience. As such, the results are inherently varied and often suboptimal. Big data approaches have emerged as an excellent decision-making support tool, but their application is limited by multiple challenges, the main one being the availability of sufficiently big datasets with good quality, representative information. An alternative approach—phenotypic personalized medicine (PPM)—finds an appropriate drug combination (quadratic phenotypic optimization platform [QPOP]) and an appropriate dosing strategy over time (CURATE.AI) based on small data collected exclusively from the treated individual. PPM-based approaches have demonstrated superior results over the current standard of care. The side effects are limited while the desired output is maximized, which directly translates into improving the length and quality of individuals’ lives.

scholarly journals Personalized Medicine in the Oncology Clinic: Implementation and Outcomes of the Johns Hopkins Molecular Tumor Board

2017 ◽  
pp. 1-19 ◽  
Author(s):  
W. Brian Dalton ◽  
Patrick M. Forde ◽  
Hyunseok Kang ◽  
Roisin M. Connolly ◽  
Vered Stearns ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Targeted Therapy ◽  
Targeted Therapies ◽  
Progression Free Survival ◽  
Molecular Profiling ◽  
Tumor Board ◽  
Free Survival ◽  
Off Label ◽  
Tumor Boards ◽  
Molecular Tumor Board

Purpose Tumor genomic profiling for personalized oncology therapy is being widely applied in clinical practice even as it is being evaluated more formally in clinical trials. Given the complexities of genomic data and its application to clinical use, molecular tumor boards with diverse expertise can provide guidance to oncologists and patients seeking to implement personalized genetically targeted therapy in practice. Methods A multidisciplinary molecular tumor board reviewed tumor molecular profiling reports from consecutive referrals at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins over a 3-year period. The tumor board weighed evidence for actionability of genomic alterations identified by molecular profiling and provided recommendations including US Food and Drug Administration–approved drug therapy, clinical trials of matched targeted therapy, off-label use of such therapy, and additional tumor or germline genetic testing. Results One hundred fifty-five patients were reviewed. Actionable genomic alterations were identified in 132 patients (85%). Off-label therapies were recommended in 37 patients (24%). Eleven patients were treated off-label, and 13 patients were enrolled onto clinical trials of matched targeted therapies. Median progression-free survival of patients treated with matched therapies was 5 months ( 95% CI, 2.9 months to not reached), and the progression-free survival probability at 6 months was 43% (95% CI, 26% to 71%). Lack of locally available clinical trials was the major limitation on clinical actionability of tumor profiling reports. Conclusion The molecular tumor board recommended off-label targeted therapies for a quarter of all patients reviewed. Outcomes were heterogeneous, although 43% of patients receiving genomically matched therapy derived clinical benefit lasting at least 6 months. Until more data become available from precision oncology trials, molecular tumor boards can help guide appropriate use of tumor molecular testing to direct therapy.

Decitabine Improves Clinical Outcomes in Severely Ill Sickle Cell Disease Patients Who Have Exhausted Standard of Care Options.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3792-3792
Author(s):  
Yogenthiran Saunthararajah ◽  
Robert Molokie ◽  
Seema Sidhwani ◽  
Santosh Saraf ◽  
Stephen Vara ◽  
...  
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Clinical Trials ◽  
Low Dose ◽  
Performance Status ◽  
Fetal Hemoglobin ◽  
Standard Of Care ◽  
Cell Disease ◽  
Off Label ◽  
Clinically Significant

Abstract Interventions such as immunization, penicillin prophylaxis, hydroxyurea and transfusion have extended life in patients with sickle cell disease (SCD). Nonetheless, these interventions are limited by toxicity or effectiveness; continued substantial morbidity and mortality in SCD indicates the need for better disease modification. In previous phase I/II clinical trials, 13 of 13 patients treated with the DNA hypomethylating agent decitabine responded with clinically significant fetal hemoglobin and total hemoglobin elevation and improvement in surrogate clinical end-points. However, in these early studies, no clinical end-points were measured and further studies have been delayed by funding issues. We describe an off-label experience in four patients with severe SCD that suggests remarkable clinical effectiveness in patients who have exhausted standard of care and are severely ill; tolerability even in the severely ill; a mechanism of action based on increased reticulocytosis in addition to increased fetal hemoglobin. All four patients had multiple alloantibodies and red-cell auto-antibodies that limited availability and increased risks of transfusion, and had previously been treated with hydroxyurea with continued clinical deterioration. Three of the four patients had relative reticulocytopenia (absolute reticulocyte count <250x109/L and hemoglobin <9g/dl) and were receiving erythropoietin or darbopoietin for more than 8 weeks with continued progressive anemia and progressive congestive heart failure. All four patients were ECOG performance status 3 and ineligible for available clinical trials. Based on the clinical trial experience conducted at our institution, decitabine therapy at 0.1–0.2 mg/kg 1–2X/week was initiated in these patients not for research purposes but with the intent to produce direct clinical benefit. The limited clinical data and potential for unanticipated toxicity was discussed in full with each patient and family members. IRB approval was obtained for a retrospective chart review. No decitabine related adverse events occurred. All patients demonstrated >2g/dl increases in hemoglobin levels with an associated improvement in clinical status - decrease in pain, improvement in performance status, improvement in congestive heart failure symptoms/signs. Upward trends in the platelet and reticulocyte counts concurrent with downward trends in the neutrophil counts were consistent with previously observed effects of low dose decitabine or the related compound 5-azacytidine. Clinically significant neutropenia was avoided by dose reductions that did not reverse the improved hemoglobin levels. The differentiation altering effects of low dose decitabine relieve SCD anemia by decreasing hemolysis (through elevated HbF) and increasing reticulocytosis. Previous clinical trials, and this off-label experience, suggest that decitabine holds remarkable promise as a disease modifying agent for SCD and β-thalassemia. Further clinical trials to confirm this impression should be supported.

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