Targeted therapy based on germline analysis of tumor-normal sequencing (MSK-IMPACT) in a pan-cancer population.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 1500-1500
Author(s):  
Zsofia Kinga Stadler ◽  
Anna Maio ◽  
Yelena Kemel ◽  
Margaret Sheehan ◽  
Erin E. Salo-Mullen ◽  
...  
Keyword(s):  
Advanced Cancer ◽  
Therapeutic Interventions ◽  
Targeted Treatment ◽  
Unknown Primary ◽  
Trial Participation ◽  
Advanced Cancer Patients ◽  
Research Setting ◽  
Therapeutic Implications ◽  
Pan Cancer ◽  
Targeted Therapeutic

1500 Background: Tumor mutational profiling for identification of somatic alterations for targeted treatment is increasingly being performed in advanced cancer patients (pts). We sought to assess the clinical utility of germline mutation profiling for targeted therapeutic interventions in a pan-cancer patient population. Methods: All pts who had germline genetic testing through a prospective protocol via a next-generation sequencing panel (MSK-IMPACT) were identified (N=11,975) from 2015-5/2019. The medical record of pts with likely pathogenic/pathogenic germline (LP/P) alterations in genes with known therapeutic targets were reviewed to identify germline-targeted treatment either in a clinical or research setting. Results: We identified 2,043 (17.1%) pts who harbored LP/P variants in a cancer predisposition genes including 777 (6.5%) in genes with potentially targetable therapeutic implications: 416 BRCA1/2, 149 DNA mismatch repair genes (Lynch syndrome, LS), 122 ATM, 45 PALB2, 26 RAD51C/D, 7 RET, 4 TSC, 3 PTCH1, 2 ALK, 1 EGFR, 1 MET and 1 KIT. Of those with advanced disease (n=554), 45.3% received targeted therapeutic treatment (Table) including 50.9% BRCA1/2, 58.3% LS (67.4% of microsatellite-high LS cases), 41.7% PALB2, 36.8% RAD51C/D and 19.3% ATM carriers. Of patients receiving a poly (ADP-ribose) polymerase inhibitor (PARP-I) in the setting of a BRCA1/2 mutation, 55.1% had breast or ovarian cancer; however, 44.8% had other tumors, including pancreas, prostate, bile duct, gastric, wherein the drug was given in a research setting. Among PALB2 pts receiving PARP-Is, 53.3% (8/15) had breast or pancreas cancer; 46.7% had cancer of the prostate, ovary or unknown primary. Conclusions: In our pan-cancer analysis, 6.5% of pts harbored a targetable germline variant highlighting the importance of germline analysis in advanced cancer pts for selection of both FDA-approved treatments and clinical trial participation with germline-targeted therapeutics. [Table: see text]

scholarly journals Investigator Disclosure and Advanced Cancer Patient Understanding of Informed Consent and Prognosis in Phase I Clinical Trials

2018 ◽  
Vol 14 (6) ◽  
pp. e357-e367 ◽  
Author(s):  
Fay J. Hlubocky ◽  
Nancy E. Kass ◽  
Debra Roter ◽  
Susan Larson ◽  
Kristen E. Wroblewski ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Informed Consent ◽  
Phase I ◽  
Advanced Cancer ◽  
Interaction Analysis ◽  
Trial Participation ◽  
Phase I Trials ◽  
Phase I Clinical Trials ◽  
Advanced Cancer Patients ◽  
Medical Benefits

Purpose: Advanced cancer patients (ACPs) who participate in phase I clinical trials often report a less-than-ideal understanding of the required elements of informed consent (IC) and unrealistic expectations for anticancer benefit and prognosis. We examined phase I clinical trial enrollment discussions and their associations with subsequent ACP understanding. Methods: Clinical encounters about enrollment in phase I trials between 101 ACPs and 29 oncologists (principal investigators [PIs] and fellows) at three US academic medical institutions were recorded. The Roter Interaction Analysis System was used for analysis. ACPs completed follow-up questionnaires to assess IC recall. Results: PIs disclosed the following phase I IC elements to ACPs in encounters: trial purpose in 40%; specific physical risks in 60%; potential specific medical benefits gained by trial participation (eg, disease stabilization) in 48.2%; and alternatives to phase I trial participation in 47.1%, with 1.1% of encounters containing palliative and 2.3% hospice information. PIs provided ACP-specific prognoses in 29.0% of encounters but used precise terms of death in only 4.7% and terminal in 1.2%. A significant association existed between PI disclosure of the trial purpose as dosage/toxicity, and ACPs subsequently correctly recalled trial purpose versus PIs who did not disclose it (85% v 13%; P < .05). Conclusion: Many oncologists provide incomplete disclosures about phase I trials to ACPs. When disclosure of certain elements of IC occurs, it seems to be associated with better recall, especially with regard to the research purpose of phase I trials.

Secondary causes of cancer-related anorexia: Recognition in daily practice by a novel checklist, a pilot study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 9058-9058
Author(s):  
A. G. Omlin ◽  
F. Strasser
Keyword(s):  
Advanced Cancer ◽  
Epigastric Pain ◽  
Daily Practice ◽  
Therapeutic Interventions ◽  
Future Research ◽  
Advanced Cancer Patients ◽  
Cross Sectional ◽  
Expert Opinions ◽  
The Impact ◽  
Control Study

9058 Background: Secondary - potentially reversible - causes of cancer-related anorexia, a common and devastating complication of advanced cancer, remain poorly recognised in daily practice. To explore the frequency of SecAn and evaluate the practice- guiding-potential (PGP) of a novel clinical assessment checklist (CL-SecAn). Methods: The 11 item CL-SecAn is based on literature review and multiprofessional clinical expert opinions. Patients rate the answers to the questions “I feel anorectic because of [i.e. stomatitis]” by an 1–4 categorical scale (no, little, moderate, a lot). Consecutive patients of an interdisciplinary palliative-oncological outpatient “nutrition & fatigue” clinic (NF-clinic) and of a multicenter cross-sectional advanced cancer pain study completed the CL-SecAn. Charts of the NF-clinic were retrospectively reviewed for onset or change of therapeutic interventions (Tx-SecAn) focused on identified causes of SecAn. Patients with (rating 3 or 4) or without (1 or 2) one of the 11 SecAn causes were compared to estimate PGP. In addition, matched (age, sex, tumor, cachexia) “regular” out-patients are compared to NF-clinic patients for Tx-SecAn. Results: SecAn was present (defined as =3/4) in 63 of 113 (56%) patients (53 NF-clinic, 60 study; f:m 45:68; age 64 [median, range 25, 88]; 30% gastrointestinal, 20% lung, 13% prostate, 10% urogenital, and 17% other cancer, 10% lymphoma). SecAn causes were: stomatitis 4%, dysgeusia 19%, dysphagia 8%, epigastric pain 9%, abdominal pain 14%, constipation19%, diarrhea 5%, defecation after a meal 2%, pain 12%, dyspnoea 3% and fatigue 13%. In 36 (32%) patients more than one cause was present. Tx-SecAn for dysgeusia was applied in 7 of 15 patients (46%) with and 3 of 38 (8%) without Sec-An Dysgeusia. For constipation, Tx-SecAn was modified in 70% with and 27% without Sec-An constipation. The other 9 Sec-An were analysed accordingly. The case-control study is currently ongoing. Conclusions: SecAn causes seem to be common in advanced cancer patients. The CL-SecAn carries a Practice-Guiding-Potential, at least for some of the 11 SecAn causes, its potential might be underrecognized in frequently treated syndromes, such as constipation. Future research will investigate further the impact of CL-SecAn. No significant financial relationships to disclose.

Examining the dilemmas of prognostic information disclosure and understanding in those with terminal cancer: In-depth interviews with advanced cancer patients in phase I trials

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 8516-8516
Author(s):  
F. J. Hlubocky ◽  
C. K. Daugherty
Keyword(s):  
Phase I ◽  
Cancer Patients ◽  
Advanced Cancer ◽  
Qualitative Interviews ◽  
Trial Participation ◽  
Phase I Trials ◽  
Advanced Cancer Patients ◽  
Prognostic Information ◽  
Treatment Benefit ◽  
Quantitative Estimates

8516 Background: Timely and accurate prognostic information is essential if patients are to make ethically appropriate medical decisions. Yet, prior research indicates advanced cancer patients (acp) with limited prognoses either misunderstand or fail to receive physician (md)-disclosed information regarding prognoses. Methods: Using semi-structured quantitative and qualitative interviews, acp were queried about prior discussions of prognosis (dop) with md and perceptions about treatment benefit. Results: To date, 87 (93%) acp receiving experimental (phase I) chemotherapy have been interviewed: median age 61 (33–82); 52% male; 80% Ca; 90% married; 58% >high school education. Quantitative interview data include: Likert scores (1–10) of likelihood of chemotherapy in: “stabilizing” cancer (mean 7.6); “halting” cancer (mean 7.1); producing “remission” (mean 6.9); and “curing” (mean 2.9). In response to a specific query, only 52% reported having dop with their md regarding life expectancy and 42% actually stated they initiated this dop. Although 45% denied any dop with md, a significant number of this group provided subsequent qualitative descriptions of dop within our interviews. As well, 61% described receiving specific quantitative estimates indicating a priori dop. When asked about their own thoughts on prognosis, only 4% described quantitative estimates or timeframes. Overwhelmingly so, patients were hopeful for a positive outcome or prolonged survival due to phase I trial participation. Several were currently deferring further dop. Conclusions: Despite prior data indicating that acp have a poor understanding of their prognoses, our findings indicate that at least 75% of interviewed acp recalled having had at least one specific dop and two-thirds describe having received a quantitative estimate of their prognosis. The majority of acp in phase I trials continue to have significant beliefs in the benefits of further therapy. No significant financial relationships to disclose.

High dose-intensity of irinotecan administered every 3 weeks in advanced cancer patients: a feasibility study.

1997 ◽  
Vol 15 (3) ◽  
pp. 1080-1086 ◽  
Author(s):  
Y Merrouche ◽  
J M Extra ◽  
D Abigerges ◽  
R Bugat ◽  
G Catimel ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Dose Level ◽  
Advanced Cancer ◽  
Dose Intensity ◽  
Maximum Tolerated Dose ◽  
Unknown Primary ◽  
High Dose ◽  
Advanced Cancer Patients ◽  
Grade 3 ◽  
Febrile Episodes

PURPOSE To assess, on a multicenter basis, the feasibility of treating advanced cancer patients with high-dose irinotecan. PATIENTS AND METHODS Thirty-five patients who met the usual phase I criteria (26 men and nine women) were included. Primary tumor sites were colon, head and neck, unknown primary, kidney, liver, and others. All had been previously treated. Irinotecan was given at the maximum-tolerated dose (MTD) (600 mg/m2) or the level below (500 mg/m2) as a 30-minute infusion once every 3 weeks. RESULTS Eighteen patients were entered in the four participating centers at the MTD of 600 mg/m2. This dose level was clearly shown not to be feasible: 14 patients (78%) had grade 3 to 4 neutropenia, with febrile episodes in 11 patients; grade 3 to 4 diarrhea was observed in nine patients; and one toxic death occurred. Subsequently, 17 not heavily pretreated patients were included at 500 mg/m2 and carefully monitored. The safety of this dose level was considered acceptable: 41% of patients had grade 3 to 4 neutropenia, 24% experienced grade 3 to 4 diarrhea, and no febrile granulocytopenia or toxic death occurred. Six partial responses were documented in metastatic colorectal cancer, all in patients who had previously received conventional chemotherapy, four in patients who had exhibited progressive disease under fluorouracil (5FU)-based chemotherapy. CONCLUSION We plan to study the higher dose-intensity 500-mg/m2 level on good-risk and carefully monitored patients. This could enlarge the spectrum of tumors sensitive to irinotecan and improve the already good results observed in colorectal cancers.

Clinical trial participation as part of end-of-life (EOL) cancer care: Associations with medical care near death and bereaved caregivers’ mental health.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 9102-9102
Author(s):  
Andrea Catherine Phelps ◽  
Baohui Zhang ◽  
Holly Gwen Prigerson
Keyword(s):  
Mental Health ◽  
Clinical Trial ◽  
Propensity Score ◽  
Cancer Patients ◽  
Advanced Cancer ◽  
Chart Review ◽  
Trial Participation ◽  
Clinical Trial Participation ◽  
Advanced Cancer Patients ◽  
Eol Care

9102 Background: Clinical trial participation is necessary to improve existing therapies, encouraged by national guidelines, and common among advanced cancer patients. The relationships between trial participation and important EOL outcomes such as aggressive care are unknown. Methods: Coping with Cancer Study, an NCI-funded multicenter prospective cohort study of advanced cancer patients and their caregivers, enrolled September 2002 – February 2008. Patients were interviewed at baseline, and clinical trial participation was documented by chart review. Patients were followed to death, (median 4.4 months from baseline). Medical care and quality of life (QOL) in the last week of life was assessed by caregiver interview and chart review. Caregiver interview 6 months post-bereavement assessed QOL and mental health (Structured Clinical Interview for the DSM-IV). The primary outcome was aggressive EOL care (ventilation, resuscitation, or chemotherapy in the last week of life). Secondary outcomes were bereaved caregivers’ mental health and QOL. Propensity-score weighting balanced patient characteristics (e.g. clinical variables, EOL preferences) that differed by trial participation. Propensity-score weighted regression models estimated the effect of trial participation on outcomes. Results: Of 246 patients followed to death with non-missing propensity scores, 27 were clinical trial participants. In propensity-score weighted analyses, trial participation was significantly associated with aggressive EOL care [29.6% v 9.1%; adjusted OR (AOR), 12.14; 95% CI, 3.65-40.36], ICU admission, mechanical ventilation, chemotherapy, and a trend toward inferior QOL near death (p = 0.069). Of 180 matched caregivers, trial participation predicted less mental illness [AOR, 0.15; 95% CI 0.04-0.57], major depression [AOR, 0.25; 95% CI, 0.08-0.80], but was unassociated with QOL (p = 0.15) in adjusted analyses. Conclusions: Clinical trial participation is associated with increased risk of aggressive EOL care for advanced cancer patients, but better mental health for bereaved caregivers.

The impact of physician’s sequence [1st vs 2nd] and posture [sitting vs standing] on cancer patients’ physician preference and perception of compassion

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 18513-18513
Author(s):  
E. Bruera ◽  
F. Strasser ◽  
G. Kaur ◽  
T. K. Zhang ◽  
L. Cohen ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Advanced Cancer ◽  
Clinical Care ◽  
Trial Participation ◽  
Advanced Cancer Patients ◽  
Sitting Posture ◽  
The Mean ◽  
The Impact ◽  
Financial Relationships

18513 Background: Our group previously found in a cross-over RCT in 69 advanced cancer patients [P] that the sitting posture was preferred; we also found that patients consistently chose the physician [MD] they observed in 2nd order [ASCO 2003:2958]. The effect of sequence on MD preference and perception of compassion had not been reported before. The purpose of this study was to assess if P preferred MD seen in 2nd order after controlling for posture. Methods: Advanced cancer P were randomized to observe 2 9-minute videos of a P/MD interaction. Both videos were identical except for the posture of the MD [sitting versus standing]. After a 2–3 minute assessment P were crossed-over into viewing the opposite video. Investigators were blinded to the type of video observed. P were blinded to the purpose of the study and difference between videos. Results: 168 P [98%] were evaluable. The mean perception of compassion [0 = worst, 50 = best] was 29 ± 13 for the 1st MD versus 33 ± 11 for the 2nd MD [p < 0.001]. P also preferred sitting [33 ± 11] versus standing [29 ± 12, p < 0.001]. The overall impression [0 = worst, 10 = best] for the MD seen 2nd versus 1st was 6.5 ± 2.3 versus 5.7 ± 2.7 [p ≤ 0.001]. All differences in response were independent on posture. 119/168 P [71%] perceived a difference between the 2 MDs and this difference was considered ≥ moderately important in 95 P [80%]. 76/168 P preferred the 2nd MD [45%, 95% CI, 38–53], 38/168 P preferred the 1st MD [23%, 95% CI, 16–29], and 54/168 P had no preference [32%, 95% CI, 25–39]. 49/114 P who expressed a preference perceived their preferred MD had spent more time with the P [43%]. 87/168 P preferred their MD to sit [52%] but they considered posture more important than time in 23 cases [20%], friendliness in 18 [15%], patience in 16 [14%], caring in 15 [14%], and respect in 18 [16%]. Conclusions: P prefer MDs they see in 2nd order, they have an overall better impression of them and consider them more compassionate, and they perceive that they spent more time with their P, independently on the MD’s chosen posture. Most P also prefer MDs to sit but posture is rated as a relatively low priority in P/MD communication. These findings are important for clinical care and trial participation. No significant financial relationships to disclose.

Sign in / Sign up

Export Citation Format

Share Document