Dataset Information

Evaluation of personalized cancer therapies based on comprehensive genomic profiling in a middle-sized oncologic center in Austria, the University Clinic Krems.

ABSTRACT:

Background and aim

To successfully apply personalized cancer therapies, thorough understanding of the patient's tumor is needed. In-depth, comprehensive genomic profiling systems allow gathering this knowledge by testing hundreds of cancer-related genes. Several large institutions have established precision oncology programs in recent years with promising results for patients. However, especially middle-sized oncologic institutions face challenges to implement such programs. This study aims to retrospectively analyze the effects of comprehensive genomic tumor profiling with respect to feasibility and effectiveness in a middle-sized oncologic center in Austria.

Methods

From May 1st, 2016 to December 31st, 2019 patients at the University Clinic Krems, who suffered from CUP-syndromes plus patients, who were resistant to conventional therapy or have progressed after all available therapy lines, were offered to get their tumors analyzed by comprehensive genomic profiling in order to establish a customized therapy.

Results

Of 69 considered patients, 64 patients' samples could be profiled. The median number of detected alterations was 4 (minimum 0; maximum 23). Most frequent alterations were reported for TP53, KRAS and CDKN2A/B. In 13 patients (20% of 64 successful profiles), personalized therapies could be initiated. 22 patients were treated with another line of chemotherapy as no actionable alteration could be detected. Effectiveness, determined by a PFS of the newly initiated therapy longer than 130% of the last conventional therapy line, could be seen in 8 of 13 patients (61,5%) of the precision oncology cohort compared to only 3 of 22 patients (13,5%) in the chemotherapy group. Additionally, Kaplan-Meier curves of PFS demonstrate a significant benefit for personalized treated patients (p?=?0,0165 with a median PFS of 151 days, compared to 83 days in the chemotherapy group).

Conclusion

In summary, personalized cancer therapy based on comprehensive genomic profiling is effective and feasible also in the setting of a middle-sized oncologic center.

SUBMITTER: Singer J

PROVIDER: S-EPMC7907921 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Publications

Evaluation of personalized cancer therapies based on comprehensive genomic profiling in a middle-sized oncologic center in Austria, the University Clinic Krems.

Singer Josef J Brauneck Elias E Zwickl-Traxler Elisabeth E Pecherstorfer Martin M

Translational oncology 20210220 5

<h4>Background and aim</h4>To successfully apply personalized cancer therapies, thorough understanding of the patient's tumor is needed. In-depth, comprehensive genomic profiling systems allow gathering this knowledge by testing hundreds of cancer-related genes. Several large institutions have established precision oncology programs in recent years with promising results for patients. However, especially middle-sized oncologic institutions face challenges to implement such programs. This study a ...[more]

PMID: 33621740

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Project description:BACKGROUND:Patients with rare tumors may lack approved treatments and clinical trial access. Although each rare tumor is uncommon, cumulatively they account for approximately 25% of cancers. We recently initiated a Rare Tumor Clinic that emphasized a precision medicine strategy. MATERIALS AND METHODS:We investigated the first 40 patients presenting at the Rare Tumor Clinic. Next-generation sequencing (NGS) of tissue and plasma-derived, circulating-tumor DNA (ctDNA), and protein markers were assessed. RESULTS:Median age was 58 years (range, 31-78 years); 70% (28/40) were women; median number of previous systemic therapies was 2 (range 0-7). The most common diagnoses were sarcoma (n?=?7) for solid tumors and Erdheim-Chester disease (n?=?5) for hematologic malignancies. Twenty distinct diagnoses were seen. Examples of ultrarare tumors included ameloblastoma, yolk sac liver tumor, ampullary cancer, and Castleman's disease. Altogether, 32 of 33 patients (97%) with tissue NGS and 15 of 33 (45%) with ctDNA sequencing harbored ?1 alteration. Overall, 92.5% of patients (37/40) had ?1 actionable target based on either genomic (n?=?32) or protein (n?=?27) markers. In total, 52.5% (21/40) received matched therapy; 52.4% (11/21) achieved stable disease (SD) ?6 months (n?=?3), partial remission (PR; n?=?6), or complete remission (CR; n?=?2). Matched therapy resulted in significantly longer progression-free survival compared with last prior unmatched therapy (hazard ratio 0.26, 95% confidence interval 0.10-0.71, p?=?.008). CONCLUSION:Identifying genomic and protein markers in patients with rare/ultrarare tumors was feasible. When therapies were matched, >50% of patients attained SD ?6 months, PR, or CR. Further precision medicine clinical investigations focusing on rare and ultrarare tumors are urgently needed. IMPLICATIONS FOR PRACTICE:Although rare tumors are infrequent by definition, when all subtypes of rare cancers are combined, they account for approximately 25% of adult malignancies. However, patients with rare tumors may lack approved treatments and clinical trial access. This paper describes an institutional a Rare Tumor Clinic focused on a precision medicine strategy. Performing genomics and protein analyses was feasible amongst patients with rare cancers. Over 50% of patients attained SD ?6 months, PR, or CR when they received matched therapy (genomically targeted and/or immunotherapy). Further studies investigating the efficacy of the precision therapy approach among rare tumors are warranted.

Project description:IntroductionProspective clinical trials are essential to translate new therapy concepts or rather any scientific development into the medical routine. Besides a sophisticated trial protocol, the success of clinical trials depends on patient recruitment and participation. Patient recruitment remains a challenge and depends on several factors. To get a current picture of the patients' attitude, we conducted the present survey.MethodsWe designed a survey with seven questions, which was given to all oncological patients treated within a timeframe of three months between Mai and July 2017. Participation was voluntary and anonymous. The questionnaire mainly inquires patients' participation in clinical trials in a university-based setting, their attitude towards clinical trials regarding risks and benefits, and their source of information in this context.Results771 patients (1:1 male/female) participated with a median age of 61 years (range 18-91 years) with a response rate of 71.5%. Of all, 17.8% (137/771) were participating in a clinical trial. The most mentioned reason was to serve medical progress and cancer research. Out of the patients not currently participating in a trial, 79 (12.7%, 79/623) refusers named the following main reasons: extensive travel time to the clinic, no therapeutic advantage, and too time-consuming. Out of the patients not offered to take part in a trial, 265 (51.0%, 265/520) would participate if offered. Of all patients, 8.3% (64/771) used the clinics' homepage as a source of information, of those 79.7% (51/64) were satisfied with its content. To enhance patient recruitment strategies, we asked how patients wish to be informed about possible trials: More than half (52.0%) of the questioned patients preferred an individual medical consultation with their physician.We further analyzed the trial participation depending on age, gender, unit, and tumor entity. We could show a significant influence of age (p < 0.001) but not for gender (p = 0.724). The trial participation was also significantly associated with the treating unit (p < 0.001) and tumor entity (p = 0.001).ConclusionPatients are willing to participate in clinical trials. Better information strategies need to be implemented. Physicians need to be aware of running trials within their department and must counseling counsel patients effectively to improve recruitment. Trial concepts should keep in mind patients' needs including an adequate number of appointments, positive risk-benefit profiles, and information material.

Dataset Information

Evaluation of personalized cancer therapies based on comprehensive genomic profiling in a middle-sized oncologic center in Austria, the University Clinic Krems.

Background and aim

Methods

Results

Conclusion

Publications

Evaluation of personalized cancer therapies based on comprehensive genomic profiling in a middle-sized oncologic center in Austria, the University Clinic Krems.

Similar Datasets

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