Systematic vs. on-demand early palliative care in gastric cancer patients: a randomized clinical trial assessing patient and healthcare service outcomes.

PURPOSE: Early palliative care (EPC) has shown a positive impact on quality of life (QoL), quality of care, and healthcare costs. We evaluated such effects in patients with advanced gastric cancer. METHODS: In this prospective, multicenter study, 186 advanced gastric cancer patients were randomized 1:1 to receive standard cancer care (SCC) plus on-demand EPC (standard arm) or SCC plus systematic EPC (interventional arm). Primary outcome was a change in QoL between randomization (T0) and T1 (12 weeks after T0) in the Trial Outcome Index (TOI) scores evaluated through the Functional Assessment of Cancer Therapy-Gastric questionnaire. Secondary outcomes were patient mood, overall survival, and family satisfaction with healthcare and care aggressiveness. RESULTS: The mean change in TOI scores from T0 to T1 was - 1.30 (standard deviation (SD) 20.01) for standard arm patients and 1.65 (SD 22.38) for the interventional group, with a difference of 2.95 (95% CI - 4.43 to 10.32) (p = 0.430). The change in mean Gastric Cancer Subscale values for the standard arm was 0.91 (SD 14.14) and 3.19 (SD 15.25) for the interventional group, with a difference of 2.29 (95% CI - 2.80 to 7.38) (p = 0.375). Forty-three percent of patients in the standard arm received EPC. CONCLUSIONS: Our results indicated a slight, albeit not significant, benefit from EPC. Findings on EPC studies may be underestimated in the event of suboptimally managed issues: type of intervention, shared decision-making process between oncologists and PC physicians, risk of standard arm contamination, study duration, timeliness of assessment of primary outcomes, timeliness of cohort inception, and recruitment of patients with a significant symptom burden. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT01996540).

Prospective comparison of prognostic scores in palliative care cancer populations.

PURPOSE: Predicting prognosis in advanced cancer aids physicians in clinical decision making and can help patients and their families to prepare for the time ahead. MATERIALS AND METHODS: This multicenter, observational, prospective, nonrandomized population-based study evaluated life span prediction of four prognostic scores used in palliative care: the original palliative prognostic score (PaP Score), a variant of PaP Score including delirium (D-PaP Score), the Palliative Performance Scale, and the Palliative Prognostic Index. RESULTS: A total of 549 patients were enrolled onto the study. Median survival of the entire group was 22 days (95% confidence intervals [95% CI] = 19-24). All four prognostic models discriminated well between groups of patients with different survival probabilities. Log-rank tests were all highly significant (p < .0001). The PaP and D-PaP scores were the most accurate, with a C index of 0.72 (95% CI = 0.70-0.73) and 0.73 (95% CI = 0.71-0.74), respectively. CONCLUSION: It can be confirmed that all four prognostic scores used in palliative care studies accurately identify classes of patients with different survival probabilities. The PaP Score has been extensively validated and shows high accuracy and reproducibility in different settings.

Gemcitabine plus mitoxantrone and prednisone in the palliative treatment of hormone-resistant prostate cancer (HRPC): A phase II study (GOAM 01.01 study).

BACKGROUND: The present exploratory phase II study was performed to evaluate the activity and tolerability of adding a second agent (gemcitabine) to the well-tolerated mitoxantrone/prednisone regimen in patients with locally advanced or metastatic prostate cancer no longer responsive to hormonal treatment. PATIENTS AND METHODS: Forty-three patients with hormone-refractory prostate cancer (HRPC) were included in the study from May 2000 to April 2004. Their median age was 71 years (range, 56-81) and their median Karnofsky performance status (KPS) was 90 (range, 70-100). The treatment schedule consisted of intravenous (i.v.) mitoxantrone (8 mg/m2 on day 1), i.v. gemcitabine 800 mg/m2 on days 1 and 8, recycled every 21 days and oral prednisone administered at a dose of 10 mg per day. Hormonal treatment with LHRH was continued in all patients. Up to six cycles of treatment were planned in the absence of progressive disease. RESULTS: Sixteen patients had measurable disease (six patients only measurable disease, ten patients bone disease plus measurable disease) and 27 patients had only bone disease. Concerning the PSA levels, a partial response (PR) was observed in 15 patients (38%), stable disease (SD) in 16 patients (41%) and progressive disease (PD) in eight patients (21%). The objective response was evaluable in 16 patients; one patient was not evaluable because he had received only one cycle. Ten patients (63%) had SD and five patients (31%) PD. In the ten evaluable patients with objective SD, depending upon the PSA response, three PR, six SD and one PD were observed. Among the five patients who progressed, three PD and two SD were observed as a PSA response. Pain remission was recorded in 15/41 patients (36%) and the KPS remained stable in most patients. The median overall survival was 15 months (range, 1-41) (95% CI: 10-20 months). The 1-year survival rate was 61%. Hematological toxicity was mild: G 3-4 neutropenia was observed in five (12%) patients. There were no neutropenic, fevers. No significant non-hematological toxicity was observed. CONCLUSION: The mitoxantrone, gemcitabine and prednisone combination, in accordance with the present regimen, was feasible, had a palliative effect, good tolerance and antitumor activity. Nonetheless, our results do not seem to be superior to those previously described for mitoxantrone plus prednisone.

Multiple primary tumors in a family with Li-Fraumeni syndrome with a TP53 germline mutation identified by next-generation sequencing.

Li-Fraumeni syndrome (LFS) is an autosomal dominant disorder occurring at a young age that predisposes individuals to multiple forms of cancer and to a heterogeneous spectrum of malignancies. We describe the clinical history of a patient who had 5 primary malignant cancers and a familiar history consistent with LFS. We analyzed the genomic DNA of the proband and her relatives by next-generation sequencing (NGS) technology using an enrichment protocol for the simultaneous sequencing of 94 genes involved in hereditary cancers. Genetic analysis of the proband revealed a TP53 germline mutation in exon 5 determining a nucleotide alteration at codon 175 (R175H), a hot spot mutation site related to LFS and a reported pathogenic mutation. The proband daughter's and brother's DNA did not carry the TP53 mutation but they had some rare variants in common with the proband, in addition to other variants with a still unclear role. In conclusion, we identified a TP53 mutation in a patient with multiple primary tumors and a family history characterized by a severe susceptibility to cancer. The genetic analysis by targeted NGS led to the identification of the genetic background and to the exclusion of a cancer risk for the family members. Targeted NGS represents an efficient approach for the identification of mutations in families with a heterogeneous phenotype.