tbuckley/cabot-search huggingface dataset:
Mathematical analysis of benefit and risk in survival in non-small cell lung cancer (NSCLC) patients underwent postoperative adjuvant chemotherapy (AdjC) using CDDP-doublets.
Authors: I. Yoshino
Journal: Journal of Clinical Oncology (2011)

e17519 Background: AdjC for patients with completely resected NSCLC has been established modality to improve survival, however, its benefit is exclusively observed for stage II or IIIA patients. This may be explained by that AdjC possesses substantial risk of shortening survival in patients with early stages who are possibly cured by surgery alone. This analysis was performed to clarify whether difference of survival benefits among stages by AdjC is attributed to substantial risk of survival. Methods: Potential rescue rate (X: rate of rescue among patients with micro-residual disease after surgery) and potential life-threatening rate (Y: rate of death among patients cured by surgery alone) of the AdjC were hypothesized to be constant in each study and calculated through resolution of simultaneous equations according to the reported data of plural stages from the studies (LACE, IALT, ANITA, and JBR10) as follows; Potential rescue rate by AdjC = Survival rate of adjuvant therapy group – survival rate of surgery alone group = death rate of S · X – death rate of S · XY – survival rate of S· Y. Results: From the LACE, X and Y were calculated as 0.3 and 0.2, respectively. According to the above X and Y, theoretical benefits of 5-year survival (5ys) by adjuvant chemotherapy for stages IB and (5ys rate is 65%) and II (5ys rate is 39%) are -4.6% and 7.0%, respectively, and those are roughly equivalent to reported data of 3 and 10%. If the values of the X and Y were applied to “surgery alone group” of the IALT (the largest study in the LACE), calculated benefit at 5ys in the “AdjC group” was 6%, that was similar to the reported value. The values (0.3 and 0.2) could not be applicable to ANITA or JBR10, however, independently calculated X/Y were 0.36/0.16 and 0.79/0.26, in the respective studies. Conclusions: CDDP-doublets possess a substantial survival risk in adjuvant setting, and the different effect of AdjC among stages is possibly due to the risk/benefit balance of this modality.
Use of biopsy detail to identify subgroup risk in high-risk patients with prostate cancer.
Authors: Natasha C. Townsend, Mark K. Buyyounouski, Karen J. Ruth, Alexander Kutikov, Rosalia Viterbo, Mark Sobczak, Terry White, Eric M. Horwitz
Journal: Journal of Clinical Oncology (2013)

169 Background: High Risk (HR) prostate cancer (CaP) patients (pts) are a heterogeneous group. A recursive partitioning analysis (RPA) was performed to determine if tissue involvement could identify patients at risk for biochemical failure (BF). Methods: Between 1992-2009, 608 HR CaP pts with complete prostate biopsy detail data (% overall tissue involvement (%TI), GP45 (weighted average of %TI for Gleason Pattern 4 or 5), Gleason Score (GS)) underwent RT with/out ADT. Primary endpoint was freedom from biochemical failure (FFBF). RPA based on time to BF was used to determine cutpoints for each prognostic variable. Multivariable (MVA) RPAs were used to assess interactions of significant variables (p&lt;0.05) from univariate analysis (UVA). Results: Median follow up for PSA measurement was 45 months (3-193 mo). UVA RPA revealed significant cutpoints for FFBF for Tstage (higher risk of BF(HRBF) for T2c,T3b,T3c,T4,Tx vs lower risk of BF(LRBF) for T1,T2a,T2b,T3a, (p&lt;0.001)); GS(HRBF 3+4/5, 4+5 vs LRBF 2-6, 2+3/4, 5+3/4/5 (p=0.011); iPSA (LRBF ≤37 vs HRBF &gt;37 ng/ml (p&lt;0.001)); dose (HRBF ≤74.9 vs LRBF &gt;74.9 Gy); RT type(LRBF IMRT vs HRBF 3D-CRT, p=0.032), %TI (LRBF ≤53% vs HRBF &gt;53% (p&lt;0.001)); GP45 (LRBF ≤33% vs HRBF &gt;33%(p&lt;0.001)). Overall, FFBF at 5 yr was 79.2% (95%CI 75.0-82.8). For MVA RPA, splits are same as UVA unless noted. MVA RPA excluding GP45 and %TI showed 5 groups (5 yr FFBF 45.9%, 66.8%, 74.2%, 84.2% and 89.5%; N 16, 195, 69, 20 and 308, respectively). Tstage, iPSA, GS and RT type had significant interactions, with highest risk group including PSA &gt;44ng/ml, low Tstage and 3D-CRT, and lowest risk group including PSA ≤44 ng/ml, lower risk Tstage, and lower risk GS. Including %TI in the RPA, significant interactions were between %TI (2 splits), iPSA and GS (5 yr FFBF 50.0%, 62.5%, 71.9%, 80.4% and 92.7%; N 80, 24, 65, 233, and 206, respectively). Highest risk group included pts with %TI &gt;53%; lowest risk included pts with %TI &lt;17%, iPSA &lt;40 ng/mL, and GS lower risk. Using GP45 instead of %TI, 3 groups were found: high GP45; low GP45 and iPSA ≥40; low GP45 and iPSA&lt;40 ng/ml, (5 yr FFBF 58.9%, 67.7% and 85.5%; N 103, 63 and 442, respectively). Conclusions: Pts with &gt; 53% TI, &gt; 33% GP45 and iPSA &gt; 40 ng/ml are at highest risk of failure, and should be considered for most aggressive treatment.
CD34 Positive Cells Mobilized with Chemotherapy Plus Recombinant Human Growth Hormone (rhGH) and Recombinant Human Granulocyte Colony-Stimulating Factor (rhG-CSF) Allows Sustained Engraftment in Previously Non-Mobilizer Patients.
Authors: Camillo Almici, Rosanna Verardi, Piero Ferremi, Alessandro Re, Chiara Cattaneo, Emilio Ferrari, Simona Braga, Giuseppe Rossi, Mirella Marini
Journal: Blood (2005)
Trough blood levels of sunitinib for Asian (Japanese) patients with metastatic renal cell carcinoma and therapeutic drug monitoring.
Authors: Yoshihide Kawasaki, Shinnya Takasaki, Akihiro Ito, Koji Mitsuzuka, Shinichi Yamashita, Naoki Kawamorita, Hideaki Izumi, Hisanobu Adachi, Yasuhiro Kaiho, Masaki Tanaka, Masafumi Kikuchi, Hiroaki Yamaguchi, Nariyasu Mano, Yoichi Arai
Journal: Journal of Clinical Oncology (2016)

508 Background: The optimal blood concentration of total Sunitinib (SU) (SU + its active metabolite) is reportedly 50-100 ng/ml at trough levels according to the product literature. This is, however, based on models optimally calculated for Caucasians; hence, the desirable blood concentration for Asian patients, including Japanese, is unclear. We examined trough SU levels in Japanese patients with metastatic renal cell carcinomas (mRCC), to determine the preferred concentration of total SU and its doses. We also evaluated the efficacy and dependability of therapeutic drug monitoring (TDM) through the duration of therapy. Methods: Patients with mRCC scheduled for targeted therapy were prospectively recruited between November 2011 and August 2015. TDM of trough levels for patients treated with SU was performed on a regular basis. For this, blood samples were obtained immediately before administering SU on day 8 and day 15 after the initial administration day. Pre-therapeutic characteristics and post-therapeutic outcomes were evaluated. Relationships between pre-therapeutic characteristics, the dose of SU administered, adverse events (AEs) and total SU concentration at trough levels were determined. Results: Twenty of a total of 31 eligible patients were analyzed. Median patient age was 64 years (52-82), median BMI was 23.58 kg/m 2 (17.7-32.78), and the average duration of SU therapy was 5 months (1-40). Seventeen patients were treated with SU as first-line therapy and 3 patients as second-line therapy after interferons. Patients with trough SU levels of over 80 ng/ml following the first course needed to discontinue SU due to AEs. All of the patients who obtained long-term stable disease (SD) or partial response (PR) without any AE &gt; grade 2 were those with trough SU levels of 40-60 ng/ml. Conclusions: Our study suggests that trough total SU levels of 50-100 ng/ml are too high for Japanese people. And 40-80 ng/ml seems to be the preferable trough blood concentration of total SU after the first course of SU therapy in Japanese patients. TDM appears to be effective for the management of patients, to obtain optimal benefits of SU without AEs during therapy.
Treatment of Adenovirus Infection by Adoptive Immunotherapy: Adenovirus Capsid Hexon Is the Main Target Protein of Adenovirus-Specific Cellular Immunity.
Authors: Olga Arbach, Marco Frentsch, Barbara Chmielewicz, Marco Kaiser, Heinz Ellerbrock, Roland Lauster, Renate Arnold, Andreas Radbruch, Sebastian Voigt, Wolfram Ebell, Andreas Thiel
Journal: Blood (2006)
Do inflammatory bowel disease patients experience more toxicity after radiotherapy for colorectal and anal cancer?
Authors: Bianca W. Chang, Aryavarta M. S. Kumar, Ravi P. Kiran, Matthew F. Kalady, Ian C. Lavery, May Abdel-Wahab
Journal: Journal of Clinical Oncology (2014)

570 Background: Despite potential oncologic gains from using radiotherapy in patients with inflammatory bowel disease (IBD), it has historically been contraindicated due to increased acute gastrointestinal (GI) toxicity. Yet recent published literature is mixed with regards to toxicity outcomes in these patients. In this study, we examine GI, genitourinary (GU), and skin toxicity in IBD patients compared to non-IBD patients both treated with external beam radiation therapy (EBRT) for anal or colorectal cancer (CRC). Methods: Anal and CRC patients who received EBRT were included in this single institutional IRB-approved study. 15 IBD patients and 30 non-IBD patients were matched 1:2 based on age (±5 years), treatment year (±1 year), BMI (±10 kg/m 2 ), and clinical stage. No IBD patients had documented active disease at the time of treatment. All patients had a pathologic diagnosis of anal or CRC and received EBRT either neoadjuvantly or adjuvantly. Acute toxicity occurred within 100 days of EBRT. Data was collected via retrospective review of the treatment charts. Results: All patients received radiation doses between 45-52 Gy in 1.8Gy/fx or 2Gy/fx, delivered using AP/PA, IMRT, 3-field, or 4-field plans. There was no difference in the rate of grade 3 (20% vs 7%, p=0.19) or grade 4 (7% vs 0%, p=0.13) lower GI toxicity. There was also no difference in the incidence of GU (47% vs 30%, p=0.37), upper GI (60% vs 33.3%, p=0.08), or skin toxicity (40% vs 64%, p=0.17). Post-operatively, IBD patients had a significantly higher rate of wound dehiscence (35.7% vs 7.1%, p=0.02); however, there was no difference in the rate of bleeding (29% vs 18%, p=0.43), infection (50% vs 32%, p=0.50), or ileus (36% vs 11%, p=0.06). Conclusions: IBD patients with anal or CRC who received EBRT neoadjuvantly or adjuvantly did not experience more acute GI, GU, or skin toxicity than matched non-IBD patients with similar treatment. Post-operatively, IBD patients were more likely to have wound dehiscence, but were not more likely to have bleeding, infection, or ileus.
Ketoconazole plus dutasteride in patients with castration-resistant prostate cancer: Results of a retrospective analysis.
Authors: C. H. Ohlmann, M. Ehmann, J. Kamradt, M. Saar, S. Siemer, M. Stöckle
Journal: Journal of Clinical Oncology (2011)

e15166 Background: Due to the underlying mechanism of action by inhibiting intracelluar testosterone production and metabolism, the combination of ketoconazole and dutasteride displays a promising treatment option in patients with castrations-resistant prostate cancer (CRPC). The efficacy of this combination has already been shown in a phase-II clinical trial in asymptomatic CRPC patients that reported PSA-response rates of 56% and a biochemical progression free survival of 14.5 months. The aim of our study was to retrospectively analyse the efficacy of the combination in a cohort of patients with CRPC. Methods: Medical records of 26 patients that have been treated with ketoconazole 800mg/d, hydrocortisone 30mg/d and dutasteride 0.5mg/d (K/H/D) between 04/09 and 08/10 have been analyzed. Median age of the patients was 69.94 years with a median PSA of 84.17ng/ml before therapy. Results: 23/26 (88.5%) were eligible for analyzing PSA-response and time to PSA-progression. 7/23 (30.4%) patients experienced a PSA-reduction ≥50% and 5/23 (21.7%) showed even a PSA-reduction of ≥80%. Median time zu PSA-progression of patients with PSA-reduction <50% was 55days compared to 274days (so far) for patients who experienced a PSA-reduction of ≥50% including 5/7 censored patients that did not show PSA-progression at the time of analysis. Updated results of time to progression will be presented at the meeting. Conclusions: Our results confirm the efficacy of the combination of ketoconazole, hydrocortisone and dutasteride in CRPC patients. A subset of patients benefit from treatment by a significant PSA-response leading to long-term PSA progression free survival. Identification of predicitve biomarkers to that helpt to identify patients that are most likely to benefit from treatment seems to be worthwhile.
Preoperative hyperfractionated radiotherapy (HFRT) and concomitant chemotherapy (CT) in locally advanced primary rectal cancer (LA-PRC) in elderly patients
Authors: S. Cordio, G. Vitali, M. Ronzoni, F. Marletta, G. Foresta, S. Franco, M. Reni, H. Soto Parra, G. Giannone, E. Villa
Journal: Journal of Clinical Oncology (2005)

3661 Background: The potential advantages of preoperative chemoradiation includes increased resectability, sphincter preservation (SP) and local control. We evaluated the feasibility, pathologic complete remissions (pCR) rate and SP of preoperative HFRT+CT in LA-PRC elderly pts (age ≥ 65 yrs). Patients and Methods: From 8/96 to 9/04 57 pts with LA-PRC were enrolled: M/F 40/17; median age 71 (range 65–81); median distance from the anal verge: 5 cm (range 1–14); T3/T4: 42/15.Thirty-seven out of 57 pts (65%) had invasive tumor involving distal half of rectum requiring abdominal-perineal resection. HFRT+CT consisted of 1.25 Gy twice a day with 6 hours interval (total dose 45 Gy) concomitant to continuous infusion of 5-Fluorouracil (250 mg/sqm/day). Surgery (S) was performed with total mesorectal excision technique after 6–8 wks of induction treatment. Results: All patients completed HFRT+CT and 55 underwent S (1 pt has just completed induction and 1 refused S). Fifty-three pts had curative resections and pTNM stage was as follows: pCR: 13 pts (23.6%), T1–2N0: 11, T3N0: 14, T2–3N1:12,T4N1:3. Dowstaging was observed in 35/55 pts (63%). Twenty-five out of 37 pts (67.5%) with lesions allocated in lower rectum had SP. Combined treatment was well tolerated: G3 diarrhoea and proctitis were recorded in respectively 12% and 8% of pts. Overall surgical morbidity was acceptable with no anastomotic leaks although one post-operative death was recorded. Nineteen pts were evaluable postoperatively by anorectal-manometry assessment: 12/19 (63%) showed well functioning sphincter. Adjuvant chemotherapy was performed in 16 pts with De Gramont or Mayo Clinic regimen for 4–6 months. With a median follow up of 25 months, 16 pts (28%) have died: 12 were related to rectal cancer progression and 4 were not related. Local recurrence occurred in 5 pts (8.7%) and 8 pts (14.5%) had visceral failures. Conclusion: These results demonstrate that HFRT+CT is feasible even in elderly pts obtaining similar results in term of pCR and SP as in younger pts. Longer follow up is required to confirm the benefit of combined treatment on local control rate and overall survival No significant financial relationships to disclose.
Comparison of transthoracic esophagectomy with definitive chemoradiotherapy as initial treatment for esophageal squamous cell carcinoma in patients who could tolerate transthoracic esophagectomy.
Authors: Satoru Matsuda, Yasuhiro Tsubosa, Masahiro Niihara, Katsushi Takebayashi, Keisuke Kawamorita, Keita Mori, Takahiro Tsushima, Tomoya Yokota, Hirofumi Ogawa, Yusuke Onozawa, Hirofumi Yasui
Journal: Journal of Clinical Oncology (2015)

145 Background: Transthoracic esophagectomy (TTE) and definitive chemoradiotherapy (dCRT) have been recognized as initial curative treatments for esophageal squamous cell carcinoma (ESCC). We aimed to compare TTE with dCRT as initial treatments in patients who had potentially curable ESCC and could tolerate TTE. Methods: Consecutive patients who were histologically diagnosed as ESCC with stage I/II/III (excluding cT4 or cN3) or stage IV due to supraclavicular lymph node metastasis and were planned to undergo surgery or chemoradiotherapy as an initial treatment were eligible for this retrospective study. In order to select patients who could tolerate TTE, respiratory function, ECOG PS and preoperative complications were additionally considered in patients’ selection. Patient characteristics, recurrence free survival (RFS), 3-year and 5-year overall survival (3yOS, 5yOS) and the treatments after failure of initial treatments were investigated. Results: 112 patients were included in TTE, 65 in dCRT. No significant differences were observed in age, sex and clinical stage between TTE and dCRT (stage I/II/III/IIV of 29/47/46/10 in TTE, 23/15/20/7 in dCRT). R0 resection rate was 87% in TTE and CR rate was 68% in dCRT. In intension to treat analysis, there was no significant difference in RFS of non-stage IA patients. In contrast, 3yOS was significantly longer in TTE than dCRT (TTE, 66.3%; dCRT, 51.0%; P=0.029).In non-stage IA patients, after initial treatment failure, significantly more patients could undergo local treatment (radiotherapy or surgery in TTE, surgery or endoscopic resection or photodynamic therapy in dCRT) in TTE than dCRT (TTE 74%, dCRT 40%, P=0.003). Conclusions: In patients with locally advanced ESCC who could tolerate TTE, TTE could extend short term survival, which might be encouraged by utilizing local treatment after initial treatment failure.
Potential regulators of HER2 activity in HER2-overexpressing gastric and gastroesophageal tumors: Analysis of HER3 and heregulin expression.
Authors: Arthur J. Kudla, Violette Paragas, Elena Geretti, Matthew D. Onsum, Charlotte Fenton McDonagh
Journal: Journal of Clinical Oncology (2014)

48 Background: HER2 is overexpressed in gastric and gastroesophageal junction (GEJ) tumors. Though treatment of these tumors with the HER2-targeted agent trastuzumab offers clinical benefit, patients ultimately progress. Signaling by HER2/HER3 heterodimers following activation by HER3’s ligand heregulin has been shown to be a resistance mechanism to trastuzumab. The objective of this study was to quantitate HER2, HER3 and heregulin in gastric and GEJ tumor samples to determine whether these tumors express components for signaling through this complex and thus have potential for developing trastuzumab resistance. Methods: A novel immunofluorescent assay was used to quantitate HER2 and cytokeratin in 236 gastric and GEJ tumors. Using image analysis, each cell within a section was classified as tumor or non-tumor based on cytokeratin level. HER2 fluorescence was also quantitated in each cell and converted to number of HER2 receptors per cell using a standard curve from an array of cell lines with defined HER2. The assay’s single cell output enables an assessment of HER2 heterogeneity in any tissue. In those tumors overexpressing HER2, HER3 and heregulin were quantitated using immunofluorescence as for HER2 and by RT-PCR. Results: In concordance with published data, HER2 was overexpressed in ~10% of gastric and ~20% of GEJ tumors. HER2-overexpressing tumors could be divided into two groups with levels of HER2 consistent with IHC scores of 2+ and 3+ as assessed by clinical assays. All HER2-overexpressing samples also expressed HER3 and heregulin. Heregulin expression was detected in both tumor cells and/or in adjacent stroma. Conclusions: HER3 and heregulin are present in HER2-overexpressing gastric and GEJ tumors. To evaluate the importance of HER3 and heregulin in these patients, a randomized open label second line Phase 2 trial has been initiated with MM-111, a HER2/HER3 bispecific antibody that inhibits HER3 activity in HER2-overexpressing cells by blocking heregulin binding. HER2, HER3 and heregulin expression will be retrospectively analyzed in tumor samples from patients in this trial, providing further insight into the role of this complex in gastric and GEJ cancer.
Patient-provider communication and decision making regarding adjuvant endocrine therapy-related symptom management: Provider perspectives.
Authors: Kea Turner, Cleo A. Samuel, Heidi AS Donovan, G J. Van Londen
Journal: Journal of Clinical Oncology (2016)

156 Background: Adjuvant endocrine therapy (AET)-related symptom management (SM) among breast cancer survivors (BCS) is greatly influenced by the quality of patient-provider communication; yet, few studies have examined provider perspectives on patient-provider communication and decision-making for AET-related SM. We assessed provider perspectives on AET-related SM to identify challenges and opportunities for improvement in patient-provider communication and decision-making. Methods: We conducted 3 focus groups (FGs) with a multidisciplinary group of health care providers (n = [6] physician; n = [7] non-physician) experienced in caring for BCS undergoing AET. We utilized semi-structured discussion guides to elicit provider perspectives on patient-provider communication and decision-making for AET-related SM as well as recommendations for improvement. All FGs were held at the University of Pittsburgh, audiotaped, and transcribed. We analyzed FG transcripts using qualitative software to identify key themes. Results: Providers described multiple challenges to patient-provider communication and decision-making for AET-related SM. Providers reported that BCS are often uncertain whether their symptoms are related to AET and unsure of whom to speak with about their symptoms. Providers also felt that patients are reluctant to bring up symptoms for fear that bringing up symptoms would detract from their care. Providers agreed that patient-provider communication influences BCS’ awareness and beliefs about SM. Providers indicated that provider communication strategies such as probing for symptoms, setting realistic treatment expectations, and assessing patient satisfaction with their SM plan enhances patient decision-making about AET-related SM. Conclusions: Although providers identified several challenges related to patient-provider communication and decision-making, many of these challenges are amenable to change through provider-level interventions. Future efforts aimed at improving AET-related SM should include strategies that address patient-provider communication and decision-making.