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Comprehensive Geriatric Assessment (CGA) is utilized to plan social and health care of the elderly and to complete the diagnostic-therapeutic choice of oncologist also considering early integration with palliative care. Cancer patients (pts) hospitalized aged ≥70 years were screened by the G8 questionnaire to define if necessary CGA. CGA identified: fit, unfit and frail pts. We screened 95 pts by G8 and 93 (98%) were at risk. Pts at risk, evaluated by CGA resulted: 3 fit, 45 unfit and 45 frail. 3 fit pts received standard medical or surgical therapy. 41 unfit pts (91%) received personalized care and 4 pts got worse quickly and died. The median age was 76 and median score IADL/ADL (Instrumental/Activities Daily Living) was 5. Malnutrition was present in 31% and MMSE (Mini-Mental State Examination) was normal in 62%. Among these 45 pts, 32 died with a median survival of 120 days: 14 at home, 13 in hospice and 5 during hospitalization. Among 45 frail pts, 3 received personalized care and 42 received the Best Supportive Care. The median age was 81 and the median score IADL/ADL was 2. Malnutrition was present in 55%, and MMSE was normal in 22%. Among these 45 pts 40 died with a median survival of 36 days: 12 at home, 24 in hospice, and 4 during hospitalization. Unfit pts have a better functional, cognitive and nutritional status than frail pts. Early integration between geriatric oncology and palliative care represents the possibility of create a personalized care pathway especially for frail pts.

Baseline characteristics of the patients included (PIK3CA cohort) or not (no-PIK3CA cohort) in the PIK3CA analysis.

Purpose:We explored the prognostic effect of PIK3CA mutation in HER2+ patients enrolled in the ShortHER trial.Patients and Methods:The ShortHER trial randomized 1,253 patients with HER2+ breast cancer to 9 weeks or 1 year of adjuvant trastuzumab combined with chemotherapy. PIK3CA hotspot mutations in exon 9 and 20 were analyzed by pyrosequencing. Expression of 60 genes, including PAM50 genes was measured using the nCounter platform.Results:A mutation of the PIK3CA gene was detected in 21.7% of the 803 genotyped tumors. At a median follow-up of 7.7 years, 5-year disease-free survival (DFS) rates were 90.6% for PIK3CA mutated and 86.2% for PIK3CA wild-type tumors [HR, 0.84; 95% confidence interval (CI), 0.56–1.27; P = 0.417]. PIK3CA mutation showed a favorable prognostic impact in the PAM50 HER2-enriched subtype (n = 232): 5-year DFS 91.8% versus 76.1% (log-rank P = 0.049; HR, 0.46; 95% CI, 0.21–1.02). HER2-enriched/PIK3CA mutated versus wild-type tumors showed numerically higher tumor-infiltrating lymphocytes (TIL) and significant upregulation of immune-related genes (including CD8A, CD274, PDCD1, and MYBL2, a proliferation gene involved in immune processes). High TILs as well as the upregulation of PDCD1 and MYBL2 were associated with a significant DFS improvement within the HER2-enriched subtype (HR, 0.82; 95% CI, 0.68–0.99; P = 0.039 for 10% TILs increment; HR, 0.81; 95% CI, 0.65–0.99; P = 0.049 for PDCD1 expression; HR, 0.72; 95% CI, 0.53–0.99; P = 0.042 for MYBL2 expression).Conclusions:PIK3CA mutation showed no prognostic impact in the ShortHER trial. Within the HER2-enriched molecular subtype, patients with PIK3CA mutated tumors showed better DFS versus PIK3CA wild-type, which may be partly explained by upregulation of immune-related genes.

Consort diagram of ShortHER patients for the different analyses described in the present work.

Sistem Informasi Penerimaan Pegawai Di STMIK Pelita Nusantara. Penerimaan pegawai di STMIK Pelita Nusantara masih mengirim berkas langsung ke kantor bidang akademik dalam bentuk hardcopy. Hal ini menjadi kendala mengakibatkan penumpukan berkas dan dalam verifikasi sering terjadi kesalahan. Rekrutmen menggunakan data fisik dalam verifikasi berkas lamaran yang tentunya sangat rentan hilang karena tercampur dengan berkas pelamar. Sistem informasi yang diusulkan memiliki beberapa keunggulan dan perbedaan dari sistem yang sedang berjalan, sistem yang diusulkan secara langsung sehingga lebih mudah digunakan, integritas data terjaga tidak akan memakan waktu yang lama dalam mengolah data, telah disediakan pencetakan laporan-laporan dan fasilitas lainnya yang akan memudahkan user untuk menggunakan sistem ini. Tujuan penelitian antara lain merancang sistem penerimaan pegawai dan mengimplementasikan sistem penerimaan pegawai pada STMIK Pelita Nusantara. Sistem yang dibangun mengimplementasikan tahapan pengembangan software, analisa, design, implementasi sehingga menghasilkan suatu sistem penerimaan pegawai yang meliputi penginputan data pelamar, tes seleksi dan tes wawancara yang lebih terperinci dengan memudahkan user untuk mencari pegawai yang lebih tepat dan akurat diimplementasikan dengan PHP dan My SQL. Kata Kunci : Penerimaan Pegawai, Desain, UML, Sistem Informasi, Aplikasi Abstrcat: Employee Admission Information System In STMIK Pelita Nusantara. Recruitment of employees at STMIK Pelita Nusantara still sends files directly to the academic office in hardcopy form. This becomes an obstacle in the accumulation of files and in verification errors often occur. Recruitment uses physical data in verifying application files, which of course are very vulnerable to being lost because they are mixed with other applicant files. The proposed information system has several advantages and differences from the current system, the proposed system has been automated so that it is easier to use, maintained data integrity will not take a long time to process data, because it has provided printing reports and other facilities. will make it easier for users to use this system. The research objectives include designing an employee recruitment system and implementing an employee recruitment system at STMIK Pelita Nusantara. The system built implements the stages of software development, analysis, design, implementation so as to produce an employee recruitment system which includes inputting applicant data, selection tests and more detailed interview tests by making it easier for users to find more precise and accurate employees implemented with PHP and My SQL. Keywords : Employee Admission. Design, UML, Information Systems, Applications

Previous analyses of the GIM (Gruppo Italiano Mammella) 2 study showed that addition of fluorouracil to epirubicin, cyclophosphamide, and paclitaxel in patients with node-positive early breast cancer does not improve outcome, whereas dose-dense chemotherapy induces a significant improvement in both disease-free survival and overall survival as compared with a standard schedule. Here, we present long-term results of the study.In this 2 × 2 factorial, open-label, randomised, phase 3 trial, we enrolled patients aged 18-70 years with operable, node-positive, breast cancer with Eastern Cooperative Oncology Group performance status of 0-1 from 81 hospitals in Italy. Eligible patients were randomly allocated (1:1:1:1) to one of the four following study groups: four cycles of standard-interval intravenous EC (epirubicin 90 mg/mBetween April 24, 2003, and July 3, 2006, 2091 patients were randomly assigned to treatment: 545 to q3EC-P, 544 to q3FEC-P, 502 to q2EC-P, and 500 to q2FEC-P. 88 patients were enrolled in centres providing only standard interval schedule and were assigned only to q3FEC-P and q3EC-P; thus, 2091 patients were included in the intention-to-treat analysis for the comparison of EC-P (1047 patients) versus FEC-P (1044 patients) and 2003 patients were included in the intention-to-treat analysis for the comparison of dose-dense (1002 patients) versus standard interval analysis (1001 patients). After a median follow-up of 15·1 years (IQR 8·4-16·3), median disease-free survival was not significantly different between FEC-P and EC-P groups (17·09 years [95% CI 15·51-not reached] vs not reached [17·54-not reached]; unadjusted hazard ratio 1·12 [95% CI 0·98-1·29]; log-rank p=0·11). Median disease-free survival was significantly higher in the dose-dense interval group than the standard-interval group (not reached [95% CI 17·45-not reached] vs 16·52 [14·24-17·54]; 0·77 [95% CI 0·67-0·89]; p=0·0004). The most common grade 3-4 adverse events were neutropenia (200 [37%] of 536 patients in the q3EC-P group vs 257 [48%] of 533 in the q3FEC-P group vs 50 [10%] of 496 q2EC-P vs 97 [20%] of 492) and alopecia (238 [44%] vs 249 [47%] vs 228 [46%] vs 235 [48%]). During extended follow-up, no further grade 3-4 adverse events or deaths related to toxic-effects were reported. Treatment-related serious adverse events were reported in nine (2%) patients in the q3EC-P group, seven (1%) in the q3FEC-P group, nine (2%) in the q2EC-P group, and nine (2%) in the q2FEC-P group. No treatment-related deaths occurred.Updated results from the GIM2 study support that optimal adjuvant chemotherapy for patients with high-risk early breast cancer should not include fluorouracil and should use a dose-dense schedule.Bristol-Myers Squibb, Pharmacia, Dompè Biotec Italy, Italian Ministry of Health, Fondazione Italiana per la Ricerca sul Cancro, and Alliance Against Cancer.

Background: To compare quality of life (QoL) of patients receiving early palliative care (EPC) vs . standard oncologic care (SOC). Methods: Pragmatic, multicenter, randomized trial at five University and Community Hospital Cancer Centers in Northern Italy. Advanced non-small cell lung, gastric, pancreatic and biliary tract cancer patients diagnosed within the previous 8 weeks. In the EPC arm, visits were performed systematically by a dedicated physician/nurse palliative care (PC) team, who assessed physical and psychosocial symptoms, and enacted the necessary services. In the SOC arm, PC visits were only carried out if requested. The primary outcome was the difference in the change of QoL [Functional Assessment of Cancer Therapy-General measure (FACT-G)] from baseline to 12 weeks in the two groups. Results: From November 2014 to March 2016, 281 patients were enrolled (142 EPC, 139 SOC); 218 completed FACT-G at 12 weeks. Baseline demographic and clinical characteristics were similar for the two groups. Values of FACT-G at baseline and 12 weeks were 72.3 (SD 12.6) and 70.1 (SD 15.5) for patients enrolled in the EPC arm, vs . 71.7 (SD 14.7) and 69.6 (SD 15.5) for the SOC arm, but the change scores did not differ significantly between groups. In the multivariable analysis, adjusting for QoL at baseline, two potential prospective prognostic factors were statistically significant: lung cancer (P=0.03) and interaction of living without a partner and intervention arm (P=0.01). Dying within 6 months (P Conclusions: In this study, EPC did not improve QoL in advanced cancer patients, but our findings highlight aspects which may guide future research on EPC.

Introduction Metastatic breast cancer (MBC) is a life-threatening disease, and although some data suggest a trend in survival improvement, it has not yet been unequivocally demonstrated. This study aimed to evaluate the overall survival (OS) of MBC patients, assessing its correlation with prognostic factors. Patients and Methods COSMO (Checking Overall Survival in a MBC Observational study) is an Italian longitudinal retrospective multicenter study that enrolled patients with MBC diagnosed between 2000 and 2008. The primary objective was to detect a temporal difference in OS; the secondary objective was to identify prognostic factors as causal factors of the temporal variation in OS. Results A total of 3721 of 3930 patients from 31 centers were distributed in 3 periods: 886 (23.8%), 1302 (35.0%), and 1533 (41.2%) in 2000-2002, 2003-2005, and 2006-2008, respectively. With a median follow-up of 9.3 years, median OS was 2.8 years (95% confidence interval, 2.6-2.9). No difference in OS was found in the 3 cohorts (P for trend = .563). The worst prognosis was observed for patients with triple-negative MBC (OS, 1.5 years) and for those with central nervous system metastases (1.7 years); the best prognosis was observed in those with bone metastases or nonvisceral disease (3.4 and 3.2 years, respectively) and in patients with a disease-free interval, defined as the time between resection of the primary malignancy and diagnosis of MBC, of > 2 years (3 years). Conclusions The COSMO study found improvement in OS between 2000 and 2008. Molecular subtype remained the strongest prognostic factor, and the role of other prognostic factors was confirmed, in particular disease-free interval, site of metastasis, and age.

Background Chemotherapy-induced neutropenia (CIN) has been associated with improved prognosis in several cancer conditions. Contrasting data have been produced in ovarian cancer.

Background The 8th edition of the American Joint Committee on Cancer (AJCC) staging has introduced prognostic stage based on anatomic stage combined with biologic factors. We aimed to validate the prognostic stage in HER2-positive breast cancer patients enrolled in the ShortHER trial. Methods The ShortHER trial randomized 1253 HER2-positive patients to 9 weeks or 1 year of adjuvant trastuzumab combined with chemotherapy. Patients were classified according to the anatomic and the prognostic stage. Distant disease-free survival (DDFS) was calculated from randomization to distant relapse or death. Results A total of 1244 patients were included. Compared to anatomic stage, the prognostic stage downstaged 41.6% (n = 517) of patients to a more favorable stage category. Five-year DDFS based on anatomic stage was as follows: IA 96.6%, IB 94.1%, IIA 92.4%, IIB 87.3%, IIIA 81.3%, IIIC 70.5% (P P P = 0.975). Within anatomic stage I, the outcome was similar for patients treated with 9 weeks or 1 year trastuzumab (5-year DDFS 96.2% and 96.6%, P = 0.856). Within prognostic stage I, the outcome was numerically worse for patients treated with 9 weeks trastuzumab (5-year DDFS 93.7% and 96.3%, P = 0.080). Conclusions The prognostic stage downstaged 41.6% of patients, while maintaining a similar prognostic performance as the anatomic stage. The prognostic stage is valuable in counseling patients and may serve as reference for a clinical trial design. Our data do not support prognostic stage as guidance to de-escalate treatment. Trial registration EUDRACT number: 2007-004326-25; NCI ClinicalTrials.gov number: NCT00629278.

Purpose: We explored the prognostic effect of PIK3CA mutation in HER2+ patients enrolled in the ShortHER trial. Patients and Methods: The ShortHER trial randomized 1,253 patients with HER2+ breast cancer to 9 weeks or 1 year of adjuvant trastuzumab combined with chemotherapy. PIK3CA hotspot mutations in exon 9 and 20 were analyzed by pyrosequencing. Expression of 60 genes, including PAM50 genes was measured using the nCounter platform. Results: A mutation of the PIK3CA gene was detected in 21.7% of the 803 genotyped tumors. At a median follow-up of 7.7 years, 5-year disease-free survival (DFS) rates were 90.6% for PIK3CA mutated and 86.2% for PIK3CA wild-type tumors [HR, 0.84; 95% confidence interval (CI), 0.56–1.27; P = 0.417]. PIK3CA mutation showed a favorable prognostic impact in the PAM50 HER2-enriched subtype (n = 232): 5-year DFS 91.8% versus 76.1% (log-rank P = 0.049; HR, 0.46; 95% CI, 0.21–1.02). HER2-enriched/PIK3CA mutated versus wild-type tumors showed numerically higher tumor-infiltrating lymphocytes (TIL) and significant upregulation of immune-related genes (including CD8A, CD274, PDCD1, and MYBL2, a proliferation gene involved in immune processes). High TILs as well as the upregulation of PDCD1 and MYBL2 were associated with a significant DFS improvement within the HER2-enriched subtype (HR, 0.82; 95% CI, 0.68–0.99; P = 0.039 for 10% TILs increment; HR, 0.81; 95% CI, 0.65–0.99; P = 0.049 for PDCD1 expression; HR, 0.72; 95% CI, 0.53–0.99; P = 0.042 for MYBL2 expression). Conclusions: PIK3CA mutation showed no prognostic impact in the ShortHER trial. Within the HER2-enriched molecular subtype, patients with PIK3CA mutated tumors showed better DFS versus PIK3CA wild-type, which may be partly explained by upregulation of immune-related genes.

Additional file 1. Summary of details of studies aimed at evaluating the American Joint Committee on Cancer (AJCC) 8th edition breast cancer prognostic staging.

Introduction: Outcomes for women with pT1aN0M0 breast cancers (BC) may vary by biologic subtype. A higher proportion of HER2-positive BCs diagnosed in the interval between scheduled screening rounds has been proposed to account for the more aggressive behaviour of interval cancers (IC) compared with screen-detected (SD) tumors. No data are available on the prognostic role of HER2-positive status in a general population of pT1aN0M0 breast tumors with known screening status. Methods: All incident pT1aN0M0 BCs (n=874), systematically collected by the Cancer Registries of Emilia Romagna Region (northern Italy) and diagnosed in women aged 50-69 from 2003 to 2009 were evaluated. Screening status was ascertained by reference to the Emilia Romagna Breast Cancer Screening Program (ERBSP) database. Patients unexposed to screening, with HER2 unknown primary tumor and/or who received adjuvant chemotherapy or trastuzumab were excluded from analysis. Results: Twenty percent of patients had HER2-positive tumors. Fifty-three percent of the entire study population were SD cancers, while 18% were ICs. Tumors with high histologic grade, high proliferative rate, negative estrogen receptor status, or HER2-positive status were more likely to be diagnosed in the interval between screening. At a median follow-up of 84 months, the 5-year invasive disease-free survival (IDFS) rates were 89% and 95% in patients with HER2-positive and HER2-negative tumors, respectively (P = 0.025). Notably, HER2-positive ICs showed poorer IDFS than HER2-positive SD tumors (84% vs. 95%, respectively; P = 0.04). No difference in IDFS rates were observed between HER2-positive SD cancers and HER2-negative SD cancers. Multivariable analysis of candidate prognostic factors for IDFS will be reported. Conclusions: In a general population of pT1aN0M0 early BCs with known screening status, IC detection may identify patients with HER2-positive pT1aN0M0 tumors in whom the rate of recurrence justifies consideration for systemic, anti-HER2, adjuvant therapy. Citation Format: Musolino A, Michiara M, Boggiani D, Sikokis A, Rimanti A, Pellegrino B, Silini EM, Campanini N, Barbieri E, Sgargi P, Falcini F, Pinto C. Prognostic impact of HER2 overexpression/amplification in women with pT1a N0 M0 breast cancer with known screening status: Results from a multicenter population-based cancer registry study. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-07-23.

Lapatinib enhances antibody-dependent cell-mediated cytotoxicity (ADCC) activity of trastuzumab. FcγR polymorphisms have been associated with both ADCC and clinical activity of trastuzumab in HER2+ breast cancer (BC) patients (pts). We analyzed FcγRIIa-H131R and FcγRIIIa-V158F polymorphisms in the CHER-LOB trial population of HER2+ BCs treated with preoperative chemotherapy plus trastuzumab (arm A), lapatinib (arm B) or both (arm C). Genotyping was successfully performed in 73/121 (60%) pts. A significant improvement in pathological complete response (pCR) rate was observed for the combination arm C, but only in FcγRIIIa V allele carriers (C vs A, 67 vs 27%, P=0.043; C vs B, 67 vs 22%, P=0.012). An independent interaction between arm C and FcγRIIIa V allele was found for pCR (odds ratio=9.4; 95% confidence interval, 2.3-39.6; P=0.003). No significant associations were observed between pCR and FcγRIIa polymorphism, and between pre-treatment tumor-infiltrating lymphocytes and FcγR polymorphisms. Our study provides evidence for a FcγRIIIa V allele-restricted pCR benefit from neoadjuvant trastuzumab plus lapatinib in HER2+ BC.

544 Background: We investigated the prognostic role of the PAM50 HER2-enriched (HER2-E) subtype in HER2+ early breast cancer enrolled in the randomized Phase III ShortHER trial. Methods: The ShortHER study randomized 1254 HER2+ early breast cancer patients to receive 9 weeks vs 1 year of adjuvant trastuzumab combined with chemotherapy. Gene expression measured using nCounter platform was available for 438 surgical samples. Intrinsic subtyping was determined using the research-based PAM50 predictor. Metastasis-free survival (MFS) was calculated from randomization to distant disease recurrence or death (median follow up 72 months). Uni- and multi-variable analysis were performed using Cox models. Results: PAM50 subtype distribution was: HER2-E 53% (N = 233), Luminal A 20% (N = 87), Luminal B 10% (N = 43), Normal-like 11% (N = 48) and Basal-like 6% (N = 27). HER2-E subtype was associated with hormone receptor-negative status (p < 0.001) and TILs ≥20% (p < 0.001), but not with stage and age ( < or ≥60 yrs). HER2-E subtype was associated with worse MFS vs other PAM50 subtypes overall (HR 2.78, p = 0.001), in the short (HR 2.24, p = 0.046), and in the long arm (HR 4.04, p = 0.011). Multivariable Cox model confirmed the independent prognostic value of HER2-E subtype (Table). HER2-E subtype added significant prognostic value on top of clinicopathological variables (Likelihood ratio test p < 0.001). Conclusions: HER2-E intrinsic subtype is an independent prognostic factor for HER2+ early breast cancer patients treated with adjuvant chemotherapy and trastuzumab. Integration of PAM50 subtype in prognostic algorithms can help refine risk stratification. These findings warrant independent validation. Clinical trial information: NCT00629278. [Table: see text]

ABSTRACT The standard of care for patients with local advanced or metastatic urothelial carcinoma is chemotherapy. However, results with this are rather disappointing, and validated prognostic factors and biomarkers of tumor response, which are useful in the decision-making process, are still lacking. PubMed databases were searched for articles published until November 2013. Several promising clinical and biological candidate prognostic factors or markers of tumor response to first- or second-line therapy, such as hemoglobin, performance status, visceral metastasis and ERCC1, hENT1 and EMT markers, have been identified and described in this article. In summary, clinical parameters and molecular profiling could revolutionize the management of local advanced or metastatic urothelial cancer, but an improvement in individualized therapeutic approaches still seems distant.

Although outcomes for women with breast cancers may vary by biologic subtype, patients with T1a,b N0M0 tumors have an excellent prognosis across all subgroups. HER2 overexpression occurs in 15–20% of primary breast tumors, and is associated with diminished disease-free and overall survival. The anti-HER2 monoclonal antibody trastuzumab in combination with chemotherapy is an effective treatment for all stages of HER2 positive breast cancer (bc). However, the absolute benefit decreases as the risk of recurrence lessens and no available randomized adjuvant trial has evaluated the role of trastuzumab in women with pT1a,b N0M0, HER2-positive breast tumors. These findings may explain the debate about the appropriate indication for adjuvant chemotherapy plus trastuzumab in this setting of patients. The aim of this review was to describe known and novel prognostic risk factors to be used for tailored treatment decision in pT1a,b N0M0 HER2-positive tumors. Whether patients with small HER2-positive bc may be suitable for (chemo)therapy reduction strategies, the current available data cannot exclude the need for a more aggressive treatment in a small subset of these subjects. Novel clinical prognostic factors such as interval cancer (IC) detection may help to address this clinically important controversy. A multicenter population-based cancer registry study is currently evaluating whether IC detection may identify patients with pT1a N0M0 HER2-positive tumors in whom the rate of recurrence justifies consideration for use of conventional, trastuzumab-based chemotherapy regimens.