tbuckley/cabot-search huggingface dataset:
Hand foot skin reaction (HFSR) by the multikinase inhibitors (MKIs) sorafenib and sunitinib: Impact on quality of life (QoL)
Authors: R. H. Huggins, T. M. Kuzel, R. T. Anderson, D. P. West, M. E. Lacouture
Journal: Journal of Clinical Oncology (2008)

16122 Background: The MKIs sorafenib and sunitinib have shown a survival advantage in a variety of solid tumors. However, their use is hampered by the occurrence of HFSR in 20–30% of patients (pts), which may lead to dose modification or discontinuation and affect clinical outcome. This study investigated the overall impact of HFSR on QoL and its relationship with clinical severity. Methods: We analyzed the results of a dermatology-specific QoL pt reported questionnaire, the Skindex-16 (SK16). Overall SK16 scores vary from 0 (best QoL) to 96 (worst QoL). Subdomain scores for physical (0–30), emotional (0–36), and functioning (0–30) were also assessed. Clinical severity of HFSR was determined using the NCI-CTCAE v3.0. The relationship between HFSR grade and SK16 scores was determined using the Wilcoxon rank sum test. Correlation among the domains of the SK16 were assessed using the Pearson correlation coefficient. Results: 11 pts were included in the study (mean age = 59.4, range 41–84). The mean overall SK16 score among pts was 33 ± 25.9. The highest mean subdomain scores were for physical, followed by emotional (Table). Highest rated items were pain (3.45 ± 2.5), irritation (3.18 ± 2.7) and persistence of skin condition (3.36 ± 2.1). Emotional symptoms were correlated with perceived physical symptoms at r = 0.86 (p < 0.005) and functioning at r = 0.73 (p = 0.01). The worst SK16 symptom subdomain scores and overall scores were significantly associated with the highest HFSR grades (Table). Conclusions: This study suggests that HFSR has a substantial effect on overall QoL and physical symptoms are the most critical in this population. The significant increase in SK16 score with increasing NCI-CTCAE grade supports its validity as a tool in the assessment of physical symptoms in HFSR. Emotional distress proved to be an important correlate. Our study suggests that the SK16 is a valuable supplement in assessment of HFSR, as it also reflects non-physical morbidity, particularly the emotional impact of the disease. Mean SK16 Scores by HFSR Grade SK16 Subdomain NCI-CTCAE Grade 1 (N=3) 2 (N=7) 3 (N=1) All (N=11) Physical (p = 0.013) 4 15.6 23 13.1 ± 8.1 Emotional (p = 0.051) 2 15 29 12.7 ± 12.3 Functioning (p = 0.22) 4.7 6 23 7.2 ± 7.6 Overall (p = 0.042) 10.7 36.6 75 33 ± 25.9 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Amgen, Bayer, ImClone Systems Incorporated, Onyx Amgen, Bayer, ImClone Systems Incorporated, Pfizer Oncology
HPV prevalence and prognostic value in a prospective cohort of 255 patients with locally advanced squamous cell carcinoma of the head and neck treated with chemoradiation therapy at Centre Hospitalier de l'Université de Montréal: A single-center experience.
Authors: E. Thibaudeau, D. Soulieres, B. Fortin, F. Coutlee, P. Nguyen-Tan, X. Weng, M. Audette, O. Abboud, L. Guertin, A. Christopoulos, J. Tabet
Journal: Journal of Clinical Oncology (2011)

5574 Background: HPV has recently been recognised as a good prognostic factor in head and neck (H&N) cancer. However, most of the data is derived from randomised trials with different treatment options or small heterogeneous cohorts. This trial aims to determine the prevalence and prognostic impact of HPV on overall survival (OS), disease-free survival (DFS), local regional control (LRC) and treatment toxicity, in a large cohort of patients with locally advanced SCCHN from one centre, treated with concomitant platinum-based chemoradiation therapy (CRT), followed prospectively. Methods: Prospective data on efficacy and toxicity was available for 560 patients treated with concomitant CRT. Of these, 270 fixed and paraffin embedded specimens were collected. DNA was extracted from specimens and HPV detection was performed as previously described (Coutlée, J Clin Microbiol, 2006). Analysis was performed using Kaplan-Meier survival curves, Fisher's test for categorical data and log-rank statistics for failure times. Results: Median follow-up was 4.7y. DNA extraction was successful in 255 cases. HPV prevalence was 68.6%, and 53.3% for HPV-16 specifically. For HPV+ and HPV- respectively, median LRC were 8.9 and 2.2 years (log-rank p = 0.0002), median DFS were 8.9 and 2.1 years (log-rank p=0.0014) and median OS were 8.9 and 3.1 years (log-rank p=0.0002). Survival was statistically significantly different based on HPV-genotype, stage, treatment period and chemotherapy regimen. COX adjusted analysis for T, N, age, and treatment remained significant (HR 0.45, p=0.004). Subgroup analysis for genotype, TNM, primary site and chemotherapy regimen will be presented at the meeting. Conclusions: An increasing proportion of oropharyngeal cancer is linked to HPV. This large study with a cohort from one centre confirms that HPV status is strongly associated with improved prognosis among H&N cancer patients receiving CRT, and should be a stratification factor for clinical trials including H&N cases. Toxicity of CRT is not modified for the HPV population.
Substratification of 70-gene high-risk breast cancers with a validated 80-gene molecular subtyping profile.
Authors: F. de Snoo, B. Chan, P. Roepman, R. A. Bender, A. Glas
Journal: Journal of Clinical Oncology (2010)

10615 Background: Classifying breast cancer into molecular subtypes has previously shown to be of potential use for further treatment guidance. Here we demonstrate how patients classified as high (or low) risk by MammaPrint can be further stratified into molecular subgroups by a newly developed and validated 80-gene molecular subtyping profile (BluePrint). Methods: This validation study was carried out on a gene expression dataset (Desmedt et al., ClinCRes 2007) of 198 frozen archival breast cancer samples that were also part of the TRANSBIG MammaPrint independent validation study (Buyse et al., JNCI 2006). These patients from 5 European hospitals had T1-2N0M0 invasive breast cancer, median age 47 years, median follow-up 14 years, without adjuvant treatment. Results: The 70-gene MammaPrint profile classified 124 out of 187 breast tumors (66%) as high risk and 63 (34%) as low risk. The 124 MammaPrint high-risk tumors were then further substratified with BluePrint into 48% (60) luminal-type, 21% (26) as ERBB2-type and 31% (38) as basal-type. Kaplan Meier analysis of these substratified groups shows nearly identical 10 year DMFS rates: luminal-type tumors 66%, ERBB2-type tumors 53%, basal-type tumors 62%, respectively, a similar survival as the original unstratified MammaPrint high-risk group (64%). Similarly, BluePrint stratified low-risk MammaPrint patients (63) all showed invariable good outcome (10 yr DMFS > 95%), including no distant metastases for basal and ERBB2-type (small) subgroups for a 10-year time period. Conclusions: The molecular subtyping profile BluePrint can classify MammaPrint high-risk breast tumors into biologically different molecular subgroups. We and others have shown that breast tumors of distinct molecular subtype have different benefit from (neo)adjuvant chemotherapy, ranging from minimal response in luminal- to substantial response for ERBB2- and basal-type tumors. Further substratification of MammaPrint high-risk patients may therefore be useful for developing subtype specific treatment regimens and potentially useful for future treatment decisions. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Agendia
Promoting excellence in COAD care – Through a community multidisciplinary team approach
Authors: D. Liu, K.M. Lo, Y.H. Leung, H.M. Ma, H.S. Chan, S.S. Ho
Journal: European Respiratory Journal (2011)

Background: It was estimated that the prevalence of COPD among the elderly Chinese living in Hong Kong was 25.9%.

Methods: The COAD Alliance Community Program was designed and carried out by a community hospital in Hong Kong. It involves a multidisciplinary team of specialists via a community outreach approach. The highly dedicated team includes respiratory physicians, physiotherapists, occupational therapists, community outreach nurses, and other community based specialists. High risk patients with more than 3 emergency room or hospital admissions per year were identified and recruited into the program. They were then assessed by case managers who were responsible organizing the community based services for these patients. Services provided include advice and information provision, self care management at home, outreach nursing visits, outpatient physiotherapy sessions and emotional/counseling support. These patients' “pre - program” and “post - program” emergency room admission rates, inpatient admissions and hospital inpatient bed-days were recorded and tabulated.

Results: 100 patients were recruited into the COPD Alliance Community Program. Six patients died during this period, with 94 patients remaining for analysis. Reduction in AED attendance (mean number of admission of 2.38 pre program c.f 1.68 post program) and medical ward admissions (1.6 c.f 0.85) was evident. There is also a significant reduction in hospital inpatient bed-days (8.16 days pre program c.f. 4.42 days post program, p = 0.05). Total cost reduction is 215,028 Euros.

Conclusion: The multidisciplinary approach was effective in reducing emergency room attendances, inpatient bed –days and total health expenditure.
Increased Risk of Cutaneous Squamous Cell Carcinoma After Vismodegib Therapy for Basal Cell Carcinoma
Authors: Shalini V. Mohan, Julia Chang, Shufeng Li, A. Solomon Henry, Douglas J. Wood, Anne Lynn S. Chang
Journal: JAMA Dermatology (2016)

<h3>Importance</h3> Smoothened inhibitors (SIs) are a new type of targeted therapy for advanced basal cell carcinoma (BCC), and their long-term effects, such as increased risk of subsequent malignancy, are still being explored. <h3>Objective</h3> To evaluate the risk of developing a non-BCC malignancy after SI exposure in patients with BCC. <h3>Design, Setting, and Participants</h3> A case-control study at Stanford Medical Center, an academic hospital. Participants were higher-risk patients with BCC diagnosed from January 1, 1998, to December 31, 2014. The dates of the analysis were January 1 to November 1, 2015. <h3>Exposures</h3> The exposed participants (cases) comprised patients who had confirmed prior vismodegib treatment, and the nonexposed participants (controls) comprised patients who had never received any SI. Because vismodegib was the first approved SI, only patients exposed to this SI were included. <h3>Main Outcomes and Measures</h3> Hazard ratio for non-BCC malignancies after vismodegib exposure, adjusting for covariates. <h3>Results</h3> The study cohort comprised 180 participants. Their mean (SD) age at BCC diagnosis was 56 (16) years, and 68.9% (n = 124) were male. Fifty-five cases were compared with 125 controls, accounting for age, sex, prior radiation therapy or cisplatin treatment, Charlson Comorbidity Index, clinical follow-up time, immunosuppression, and basal cell nevus syndrome status. Patients exposed to vismodegib had a hazard ratio of 6.37 (95% CI, 3.39-11.96;<i>P</i> &lt; .001), indicating increased risk of developing a non-BCC malignancy. Most non-BCC malignancies were cutaneous squamous cell carcinomas, with a hazard ratio of 8.12 (95% CI, 3.89-16.97;<i>P</i> &lt; .001), accounting for age and basal cell nevus syndrome status. There was no significant increase in other cancers. <h3>Conclusions and Relevance</h3> Increased risk for cutaneous squamous cell carcinomas after vismodegib therapy highlights the importance of continued skin surveillance after initiation of this therapy.
Does HER2/neu expression affect adjuvant treatment choices in routine clinical practice?
Authors: O. Pagani, M. Ruggeri, T. Rusca, R. Graffeo, E. Gallerani, M. Locatelli, M. Conti Beltraminelli, S. Longhi, L. Mazzucchelli, A. Goldhirsch
Journal: Journal of Clinical Oncology (2006)

10667 Background: HER2/neu (HER2) amplification is a recognized independent prognostic and predictive factor. We retrospectively examined the correlation between HER2 expression and adjuvant therapy in patients (pts) with early breast cancer (EBC) at our Institution (IOSI). Materials and Methods: From January 2003, 326 consecutive pts with EBC have been treated at IOSI and all clinical and pathological data have been prospectively collected into a specifically designed data base (CARMA). HER2 expression was assessed by the c-erbB-2 oncoprotein antibody (NCL-L-CB11) in 309 pts (95%). FISH was not routinely performed. Endocrine responsiveness (ER+) is defined as Er and/or PgR expression by immunohistochemistry. Results: Overall, 58 pts (19%) had HER2+ disease. FISH was performed in 15 pts (24%) with doubtful antibody overexpression (2+) and did not confirm HER2 amplification in 4 cases (27%). Nodal involvement was not assessed in 1 HER2+ (2%) and in 12 HER2- pts (5%) due to advanced age. Menopausal status did not differ in HER2 positive and negative pts (29% and 27% premenopausal pts, respectively). The distribution of adjuvant chemotherapy (CT) according to tumour characteristics in HER2 positive and negative pts was as follows: An anthracycline-containing regimen was chosen in 88% of HER2+ pts receiving adjuvant CT as compared to 70% of HER2- pts. Outside of a clinical trial adjuvant Tamoxifen was given to 57% of HER2+/ER+ pts as compared to 75% of HER2−/ER+ pts. Conclusions: Overall, HER2+ pts showed less endocrine responsiveness (64% versus 88%) and more extensive nodal involvement (43% versus 30% with &gt;3 positive nodes) as compared to HER2− pts. A greater proportion of HER2+ women received adjuvant CT, irrespective of other prognostic and predictive factors. In particular, a significant higher proportion of HER2+ pts with minimal nodal involvement (1–3 positive nodes) and ER+ disease received CT as compared to the equivalent HER2- subset (45% versus 26%, respectively). [Table: see text] No significant financial relationships to disclose.
Intensive Care of Patients with HIV Infection
Authors: Michael Saccente
Journal: New England Journal of Medicine (2006)

Huang et al. suggest several factors to consider before the initiation of antiretroviral therapy in critically ill patients with HIV infection but they do not discuss the implications of such therapy regarding adherence issues. Although adherence approaches 100% during hospitalization a subgroup of patients will not take their medications after discharge. Factors associated with decreased adherence (substance abuse depression a lack of social support and a lack of insurance coverage to pay for medications) should be addressed before antiretroviral therapy is begun. It is extraordinarily difficult to try to resolve these issues during hospitalization for a critical illness.  (excerpt)
MDM2 309 and TP53 Arg72Pro single nucleotide polymorphisms (SNPs) and clinical outcome in advanced lung cancer patients
Authors: S. Novello, G. Mandrile, D. F. Giachino, P. Ghio, G. Selvaggi, D. Gregori, M. De Marchi, G. V. Scagliotti
Journal: Journal of Clinical Oncology (2007)

7636 Background: The TP53 Arg72Pro (rs1042522:C&gt;G) and MDM2 SNP309 (rs2279744:T&gt;G) SNPs of the DNA damage response pathway have been shown to affect lung cancer risk. We aimed to investigate their relationship with the clinical outcome of chemotherapy (CT). Methods: We prospectively recruited 426 consecutive patients with advanced disease (352 NSCLC and 74 SCLC, 57% metastatic) referred for chemotherapy at our institution from July 2002 to January 2006: 82% male, median age at diagnosis 63 years, 56% current and 11% never smokers, 81% receiving combined platinum CT. Median follow up time was 10.5 months. Controls were 254 medical students. We designed specific TP53 and MDM2 primers for typing both SNPs using the Pyrosequencing assay. Results: Patients genotype frequencies were: TP53 Arg/Arg 51%, Arg/Pro 40%, Pro/Pro 8%, (61%, 35%, 4% among controls, p=0.02), MDM2 T/T 37%, T/G 46%, G/G 17%, (31%, 55%, 14% among controls, p=0.07). Both groups were in Hardy-Weinberg equilibrium. At multivariable analysis adjusted for gender, smoking status, type of chemotherapy, disease stage, and side effects, survival was significantly associated with performance status (PS) [HR 1.54 (1.2–2.0)], histology [SCLC vs. NSCLC - HR 1.51(1.1–2.1)] and objective response [yes vs. no HR 0.56 (0.4–0.7)] but with neither SNP; in contrast, grade 3–4 toxicity and objective response were concomitantly associated with the SNPs of TP53 [Pro carriers vs. Arg/Arg HR 1.40 (1.1–1.8) and 1.44 (1.0–2.0)] and MDM2 [GG vs. TT 0.57 (0.4–0.9) and 0.61 (0.4–0.97)]. These findings are in agreement with the notion that MDM2 GG homozygous cells express higher levels of mdm2, thus attenuating the p53 pathway, but don’t easily fit with the alleged greater apoptotic potential of p53 Arg72. We also observed significant associations of toxicity with platinum therapy, of objective response with histology and of both outcomes with PS (not shown). Conclusion: The study provides preliminary evidence that germ-line TP53 and MDM2 SNPs affect toxicity and objective response to CT in lung cancer patients, probably depending on a variable DNA damage response but not survival time that may mainly result from the tumor aggressiveness and somatic mutational status. [Table: see text]
Lurbinectedin (PM01183), an active compound in platinum-resistant/refractory ovarian cancer (PRROC) patients: Results of a two-stage, controlled phase II study.
Authors: Andres Poveda, Dominique Berton-Rigaud, Isabelle Laure Ray-Coquard, Jérôme Alexandre, Magali Provansal, Arturo Soto, Carmen Maria Kahatt, Sergio A. Szyldergemajn, Antonio Nieto, Cristian Fernandez, Eva Guerra Alia, Antonio Casado, Antonio Gonzalez-Martin, Jose Maria Del Campo
Journal: Journal of Clinical Oncology (2014)

5505 Background: PM01183 is a new anticancer agent that blocks the trans-activated transcription and induces the formation of double-strand breaks in a wide range of cancer cell lines, including platinum-resistant (Pt-res). Methods: PRROC patients (pts) with less than 3 prior chemotherapy (CT) containing lines, adequate organ function and performance status (PS) 0-2 were included. The primary endpoint was overall response rate (ORR) (by RECIST v1.1 and/or Rustin criteria). Secondary endpoints were progression free survival (PFS), overall survival (OS) and safety. Pts were treated with i.v. PM01183 (P1), 7 mg flat dose, q3wk in the first stage. In the second stage, pts were randomized (1:1) to PM01183 (P2) or topotecan (T) (standard or weekly regimen). Cross-over to the P2 arm was allowed after progression to T. Results: 81 pts were included (P1/P2/T: 22/30/29). Global median characteristics of pts were balanced: age 61 years; PS 1; Pt-res (P1/P2/T: 16/17/16 pts); prior bevacizumab: 18.5% of pts, median prior advanced chemotherapy lines: 1 in each arm. Efficacy results are summarized in the Table. The most common PM01183 related AEs were neutropenia (Gr 3-4, 85%), febrile neutropenia (23%), thrombocytopenia (Gr 3-4, 29%), nausea/vomiting (Gr 3, 16%) and fatigue (Gr 3, 37%) Conclusions: PM01183 is an active drug in Pt-res/Pt-ref ovarian cancer. The study has met the primary endpoint, showing statistically significant superiority over T in terms of ORR, PFS and OS. The safety profile is predictable and manageable; prophylactic G CSF is recommended. A phase III study in Pt-res ovarian cancer is planned. PM01183 (n=51) Topotecan (T) (n=29) p-value First stage (P1) (n=22) Second stage (P2) (n=29) OR [n (%)] CR 0 (0) 1 (3) 0 (0) - PR §6 (27) 4 (14) 0 (0) SD 12 (55) 13 (45) 15 (52) PD 4 (18) 10 (34) 14 (48) Treatment failure 0 (0) 1 (3) 0 (0) ORR (%) (95% CI) 22 (11-35) - 0.006 Pt-res 30 (16-49) - 0.002 Pt-ref 6 (0-27) - 1 DCR (%) 71 52 - PFS (months) * 3.9 2.0 0.003 Pt-res 4.5 7.1 1.7 0.002 Pt-ref 2.9 1.4 2.7 0.809 OS (months) + 10.6 5.7 0.029 Pt-res 12.6 Not reached 7.0 0.053 Pt-ref 12.6 8.7 5.4 0.253 Abbreviations: Pt-ref, platinum-refractory; DCR, disease control rate. §2 PRs by Rustin criteria, *events: 81%; +events: 64%.
O-009 Prognostic value of BRAFV600E and KRAS exon 2 mutations in microsatellite stable stage III colon cancers from patients treated with FOLFOX + /- cetuximab: A pooled analysis from PETACC8 and N0147 trials
Authors: J. Taieb, K. Le Malicot, F. Penault-Llorca, O. Bouche, Q. Shi, S. Thibodeau, J. Tabernero, E. Mini, Z. Zaanan, R. Goldberg, G. Folprecht, J.L. Van Laethem, D. Sargent, S. Alberts, P. Laurent Puig, F. Sinicrope
Journal: Annals of Oncology (2015)
Results from year 1 of an embedded supportive oncology practice.
Authors: Bethann Scarborough, Emily Chai, Randall F. Holcombe, Eric Lee, Nathan Goldstein
Journal: Journal of Clinical Oncology (2014)

40 Background: We present the findings from our first year of a Supportive Oncology practice embedded in a quaternary care center’s outpatient cancer practice. Methods: One palliative medicine physician saw patients 4 days per week. Oncologists made referrals for symptom management, psychosocial support, advance care planning, or by predetermined triggers for palliative care. Results: 239 patients were referred for a total of 821 visits. Palliative care referrals increased over time; 0.6% of the cancer center’s patients were referred in the first quarter and 1.5% were referred in the third quarter. Referral reasons included symptom management/support (90%), goals of care (5%), or triggers (6%). Six to 9 symptoms were addressed at 41% of visits. Sixteen percent of patients initially referred for symptoms were later seen for conversations regarding goals of care. Of these patients, 76% discussed goals of care with their oncologist, 61% were referred to hospice and 47% enrolled in hospice. Supportive oncology visits were associated with decreased health care utilization, with a downward trend in Emergency Department visits (0.82 vs. 0.72 per patient) and inpatient admissions (0.91 vs. 0.84 per patient) after the initial palliative care visit compared to use before the visit. Approximately 17% of all Supportive Oncology patients enrolled in hospice. Conclusions: Our first year of an embedded palliative care practice focused on building collaborative relationships. The steady referral growth over time indicates that oncologists increasingly accepted the program. While only a small proportion of patients were referred, the high visit complexity reflects this population’s acuity. Decreased health care utilization may be due to better symptom control or care aligned with patients’ values. Early referrals for symptom management facilitate goals of care discussions later on, and the importance of delivering a unified message on treatment options is seen in the hospice referral rate of 61% for the subset of patients who discussed goals of care with palliative care and oncology. Embedding palliative care in oncology fosters expert symptom management, seamless communication, and trusting relationships between oncologists, palliative care, and patients.