bluuebunny/crossref_metadata_2025 huggingface dataset:
A phase I study of S-1 administration and a 24-h infusion of cisplatin plus paclitaxel in patients with advanced gastric cancer
Authors: Iwase H. , Shimada M. , Tsuzuki T. , Okeya M. , Kobayashi K. , Hibino Y. , Watanabe H. , Horiuchi Y. , Goto H.
Published: March 2020

4074

Background: S-1 may have a major role in the treatment of gastric cancer as single agent or as a component of combination chemotherapy in Japan. We previously reported a multicentric phase II study of S-1 combined with a 24-h infusion of cisplatin in patients with advanced gastric cancer. This combination was active, safe and had the possibility of being combined with other anticancer drug. Combination chemotherapy with S-1 and cisplatin plus paclitaxel for advanced gastric cancer might yield a stronger antitumor effect. The objective of this study was to determine the dose-limiting toxicity (DLT), the maximum tolerated dose (MTD), the recommended dose (RD), and the preliminary antitumor activity of S-1 and cisplatin plus paclitaxel for advanced gastric cancer. Methods: Paclitaxel was administered on day 1. A fixed dose of S-1 (70 mg/m2/day) was orally administered for 14 consecutive days from day 1, and a 24-h infusion of a fixed dose of cisplatin (60 mg/m2) was administered on day 14 of every 28-day cycle. Four dose escalation levels of paclitaxcel were studied (120, 140, 160, and 180 mg/m2). The DLT was defined as any of the following: grade 3 neutropenia lasting more than 5 days, grade 4 hematological toxicity, grade 3 non-hematological toxicity, or treatment delay of greater than 2 weeks as a result of toxicity. Results: Twenty patients were enrolled. Hematological and non- hematological toxicity of over grade 2 was not observed at dose level 1 and 2. Three patients started at dose level 3. One developed grade 3 neutropenia for 5 days following by grade 2 neutropenia lasted more than 10 days. Five more patients were added at this level. The treatment was delayed over 2 weeks in 1 out of 8 patients. Three patients started at dose level 4. One developed grade 3 neutropenia and needed longer than 14 days to recover. Three patients added this level. In total, at dose level 4 the treatment was delayed over 2 weeks in 3 out of 6 patients as a result of neutropenia. We considered level 4 is the MTD and the RD of paclitaxcel was 160 mg/m2 (dose level 3). The overall response rate was 75%. Conclusions: Triple combination chemotherapy consisting of S-1, cisplatin, and paclitaxel showed a tolerable dose of adverse reactions and favorable antitumor activity for gastric cancer.

No significant financial relationships to disclose.
Phase II study of neoadjuvant chemotherapy (NAC) with S-1 and cisplatin (CDDP) for patients (pts) with metastatic or locally unserectable gastric cancer (MGC)
Authors: Nashimoto A. , Yabusaki H. , Nakagawa S.
Published: March 2020

4078

Background: To improve the poor prognosis of pts with MGC, we conducted a phase II study to evaluate the feasibility and efficacy of intensive NAC to enhance surgical respectability and survival. Methods: Eligible criteria included histologically proven metastatic or locally unserectable gastric adenocarcinoma and measurable or evaluable disease, PS 0–2 and sufficient organ functions. The primary endpoint was overall survival and the secondary endpoints were overall resonse rate (ORR) and toxicities. Since Oct. 2000, chemotherapy-naïve 120 pts with MGC have received S-1 (80 mg/m2 orally intake for 21 consecutive days) and CDDP (50 mg/m2 intravenous drip infusion on day 8) as NAC. Treatment was repeated every 5 weeks. The median administered courses were three (range: 1–7), and median follow up periods were 13.8 months. Results: The proportion of the duration as an outpatient- therapy was 86%. 77.5% of pts (93/120) went to surgical resection; 36 had distal gastrectomy and 57 had total gastrectomy. ORR was 62.5% (CR 1, PR 74), and 61.7%, 75.7%, 28.6% and 23.8% for primary lesion, metastatic lymph nodes, liver metastases and peritoneal metastasis, respectively. Toxicity (grade 3/4): neutropenia 7.5%, thrombocytopenia 6.7%, anemia 6.7%, anorexia 5.8%, nausea 2.5%; no treatment related death. Survival: median 23 months; 1 year 79%; 4 year 31% in all pts, and 42 months; 83%; 38% in pts with gastrectomy, respectively. In univariate analyses, overall survival (OS) was predicted by the responder, limited tumor location, H0, P0, but not by age, sex, histological type, gross type, T-factor, N-factor, or performance status. In multivariate analyses, H0, P0 and responder independently predicted OS. In pts with gastrectomy, H0, curative resection, PS0 and responder predicted OS. Conclusions: NAC with S-1 and CDDP was feasible and useful for pts with MGC and resulted in a promising survival rate.

No significant financial relationships to disclose.
The utility of PET scanning in the management of squamous cell carcinoma of the anus
Authors: Nagle D. , Henry D. , Iagaru A. , Mastoris J. , Chmielewski L. , Rosenstock J.
Published: March 2020

4152

Background: PET scanning is an established modality that is useful in the clinical management of squamous cell carcinoma (SCC) of the head and neck and esophagus. This study evaluates the usefulness of PET scans in the management of anal SCC. Methods: Prospective case series of all patients treated for SCC of the anus between 2002 and 2006 in a multi-disciplinary oncology practice group. All patients had staging studies at diagnosis of anal SCC that included CT scan of the chest/abdomen/pelvis and PET scan. All patients with palpable inguinal adenopathy or PET scans positive for inguinal adenopathy underwent fine needle aspiration (FNA) of inguinal nodes. All patients were evaluated by physical exam (PE) and biopsy (Bx), when appropriate, within 3 months of completing treatment. All patients who completed combined chemoradiation for anal SCC and had a post-treatment PET scan were included in this study. Results: 14 of 20 treated patients met criteria for this study. Sensitivity of pre-treatment PET scan was 100% for primary tumor. Extra-pelvic sites with PET SUV<4.0 were uniformly negative for tumor. 66% of inguinal nodes identified by PET scan were FNA positive for metastatic disease. Post-treatment, combined PE and Bx accurately predicted presence or absence of disease in 93%. Post-treatment scans were obtained a mean of 7.6 months after chemoradiation (range 1 to 42 months). In these patients, PET scan sensitivity = 50%, specificity = 72%, predictive value positive (PVP) = 50%, predictive value negative = 80%. 64% of scans were performed within 6 months of treatment; in these, PVP = 33% and PVN = 66%. Conclusions: PET scanning for anal SCC provides accurate staging of disease at presentation and may alter treatment planning by identifying inguinal node involvement not apparent on clinical examination. In this series, PET scan results did not change post-chemoradiation management in any case. Importantly, resolution of primary tumor defined by PET scan was accurate only 80% of the time. PE and Bx within 3 months of treatment were more accurate than PET scan in assessing disease. Post-treatment evaluation of anal SCC should continue to include careful PE, CT scan and Bx when appropriate.

No significant financial relationships to disclose.
Single versus sequential high-dose chemotherapy (HDCT) in patients with relapsed or refractory germ-cell tumors (GCT)
Authors: Lorch A. , Rick O. , Hartmann J. T. , Kollmannsberger C. , Metzner B. , Schmidt-Wolf I. , Berdel W. E. , Schirren R. , Beyer J. , Bokemeyer C.
Published: March 2020

4511

Background: Patients (pts) with relapsed or refractory GCT may be cured by HDCT. It is unknown whether single or sequential HDCT is superior. Methods: Between 11/99 and 11/04, 216 pts with relapsed or refractory GTC were treated in a prospective, randomized, multicenter phase III trial with either one cycle of cisplatin 100 mg/m2, etoposide 375 mg/m2 and ifosfamide 6 g/m2 (VIP) plus three cycles of high-dose carboplatin 1500 mg/m2 and etoposide 1500 mg/m2 (CE, arm A) or three cycles of VIP plus one cycle of high-dose carboplatin 2200 mg/m2, etoposide 1800 mg/m2 and cyclophosphamide 6400 mg/m2 (CEC, arm B) followed by reinfusion of autologous peripheral blood progenitor cells. Primary study endpoint was the event-free survival (EFS) one year after randomization. Secondary endpoints were progression-free survival (PFS), overall survival (OS) and toxicities. An event was defined as any deviation from the planned treatment, relapse, progression or death from any cause. The planned study size was 230 pts to detect a difference of 15% with an alpha error of 5% and a power of 80%. Results: The study was stopped after recruitment of 216 pts due to excess treatment-related mortality in arm B: 111 pts were randomized in arm A and 105 pts in arm B. Due to non-GCT histologies at review 5/216 pts had to be excluded from further analysis. With a median follow-up of 36 months, 109/211 (52%) evaluable pts are still alive and 91/211 (43%) are progression-free. At one year EFS; PFS and OS are 40%, 55% and 80% in arm A as compared to 37%, 49% and 61% in arm B. Treatment-related deaths mainly due to sepsis and cardiac toxicity were less frequent in arm A (4/111 pts, 4%) as compared to arm B (15/105 pts, 14%) (p = 0.01). Severe non-hematologic organ toxicities were also less frequent in arm A. Conclusions: Treatment with sequential high-dose carboplatin and etoposide is at least as effective but less toxic than single HDCT with carboplatin, etoposide and cyclophosphamide.

No significant financial relationships to disclose.
Predicting men at high risk for PSA failure after salvage radiotherapy for rising PSA following prostatectomy
Authors: MacDonald O. K. , D’Amico A. V. , Sadetsky N. , Shrieve D. C. , Bakst A. W. , Carroll P. R.
Published: March 2020

4570

Background: Single and multi-institutional reports have published results indicating 5-year PSA response rates of 30 to 50% in men following salvage radiotherapy (RT) for rising PSA after radical prostatectomy (RP) depending upon the patient and disease factors. We analyzed a longitudinal observational database of men who received salvage RT following RP for their prostate cancer to evaluate for predictors of PSA failure despite salvage RT. Methods: Data from the Cancer of the Prostate Strategic Urologic Research Endeavor database (CaPSURE) identified 5,336 men with RP between 1989 and 2004; 200 underwent salvage RT ≥6 months after RP. PSA recurrence following salvage RT was defined as a PSA >0.2 ng/mL. A measure of the association between clinical and pathologic characteristics in men experiencing PSA failure following salvage RT was examined using a chi-square metric. Univariable and multivariable analyses of predictors for PSA recurrence using a Cox proportional hazard regression model were performed. Results: After a mean follow-up of 18 months (range 1 to 131 months), 121 (62%) men experienced PSA recurrence at a mean 13.7 months after salvage RT. Significant associations between time to PSA recurrence after salvage RT were found with the clinical risk group (p < .01), clinical T category (p < .01), race/ethnicity (p = .04), extraprostatic extension (p < .01), seminal vesicle invasion (p < .01), and pre-salvage RT PSA level (p < .01). The pre-salvage RT PSA level (p = .003) and seminal vesicle invasion (p = .02) remained significantly associated with time to PSA recurrence on multivariable analysis. Conclusions: The pre-salvage RT PSA level and the presence of seminal vesicle invasion were significantly associated with time to PSA recurrence following salvage RT within the CaPSURE database. Men with these risk factors are at increased risk for PSA recurrence despite salvage RT suggesting that these men would be ideal candidates for entry onto phase III studies comparing salvage RT plus systemic therapy with salvage RT alone at the time of post-operative PSA failure.

[Table: see text]
Cancer-specific survival following radical prostatectomy or radiation therapy and short course hormonal therapy in men with localized, unfavorable-risk prostate cancer
Authors: Tsai H. K. , Chen M. , McLeod D. G. , Carroll P. R. , Richie J. P. , D’Amico A. V.
Published: March 2020

4572

Background: We estimated prostate cancer-specific mortality (PCSM) rates following radical prostatectomy (RP) or external beam radiation therapy (RT) and 6 months of androgen suppression therapy (AST) in men with unfavorable-risk prostate cancer. Methods: Between 1981 and 2002, 3,240 men with intermediate- (T2b or Gleason score 7 or prostate-specific antigen (PSA) > 10 to 20 ng/mL) or high-risk (T2c or Gleason score 8 to 10 or PSA > 20 ng/mL) prostate cancer were treated with RP (n = 2,690) or RT+AST (n = 550) and comprised the study cohort. If PSA failure occurred, defined by a postoperative PSA level > 0.2 ng/mL and rising or by the ASTRO definition following RT+AST, then men received salvage RT or life-long AST, respectively. Life-long AST was initiated if PSA failure occurred after salvage RT. Imaging of the pelvis and skeleton was negative for metastases at the time of any salvage therapy. Gray’s formulation was used to compare the cumulative incidence estimates of PCSM and to calculate the adjusted hazard ratios (HR) and associated 95% confidence intervals for initial treatment and known prognostic factors. Results: After a median follow-up time for living patients of 4.5 and 4.2 years for the RP and RT+AST cohorts, respectively, there were no significant differences in the estimates of PCSM following RP or RT+AST in men with intermediate- (p = 0.44) or high-risk (p = 0.26) disease. As shown in the Table , after adjusting for PSA level, Gleason score, and T-category, initial therapy was not significantly associated with PCSM for men with intermediate- (HR: 1.2 [95% CI: 0.3, 4.3]; p = 0.78) or high-risk (HR: 1.2 [95% CI: 0.5, 2.8]; p = 0.62) disease. Conclusion: Men with localized, unfavorable-risk prostate cancer who receive RT and short course AST as initial therapy appear to have similar PCSM rates as men who undergo initial RP followed by salvage RT and life-long AST after first and second PSA failure, respectively.

[Table: see text]

No significant financial relationships to disclose.
Talactoferrin alfa may prolong progression-free survival in advanced renal carcinoma patients
Authors: Srinivas S. , Stadler W. M. , Bukowski R. , Figlin R. , Hayes T. , Yankee E. W. , Jonasch E.
Published: March 2020

4600

Background: Talactoferrin alfa (formerly known as recombinant human lactoferrin, rhLF) is a novel immunomodulatory 80 kD protein with demonstrated oral anti-tumor properties in animal models, and promising early results in patients with advanced renal cell carcinoma (RCC) in Phase 1/2 trials. Methods: An open label Phase 2 study of Talactoferrin Oral Solution at 1.5 g talactoferrin alfa b.i.d. given up to a maximum of 4 cycles of 12 weeks on, 2 weeks off was conducted at 6 sites. Eligibility included predominantly clear cell histology, failure of at least one prior systemic therapy, tumor progression within the prior 9 months, a performance status of <2 (ECOG) and adequate organ function. The primary endpoints were the incidence of 14-week progression-free survival (PFS) and overall tumor response (by RECIST). The statistical plan specified an objective of 12.5% response rate or a progression-free survival rate of ≥40% at 14 weeks. Secondary endpoints included median PFS and median overall survival (OS). Results: Forty-four patients were enrolled. Eighteen patients (41%) were considered low risk and twenty-six (59%) considered intermediate risk based on the Memorial Sloan-Kettering Cancer Center (MSKCC) criteria. There were no talactoferrin-related Grade 3 or 4 adverse events or laboratory abnormalities. The most common related grade 1 or 2 adverse events were gastrointestinal symptoms. There was one unconfirmed tumor response and the 14-week PFS was 55%. The median PFS was 21 weeks (46 weeks and 9.4 weeks in the patients with low and intermediate risk prognostic factors, respectively). The median OS has not yet been reached. Conclusions: Talactoferrin alfa is well tolerated. The 14-week PFS met the pre-specified criteria for success (>40%). Due to the heterogeneity of tumor biology of RCC, any further evaluation of talactoferrin in this population should be in a larger randomized trial.

[Table: see text]
Outcome of patients with non-metastatic versus metastatic hormone refractory prostate cancer (HRPC) treated with second-line hormonal therapy consisting of ketoconazole (keto) plus granulocyte macrophage colony stimulating factor (GM-CSF)
Authors: Ryan C. J. , Rosenberg J. , Lin A. , Ruttner L. , Weinberg V. , Small E.
Published: March 2020

4626

Background: Second line hormonal manipulations are frequently used in pts with HRPC. It is unknown if these manipulations are more effective in patients without clinical metastases. The efficacy of a second-line hormonal manipulation (keto plus GM-CSF) was prospectively evaluated in a cohort of HRPC patients with and without metastases. Methods: Eligible pts had progressive HRPC by consensus criteria, no prior immunotherapy, chemotherapy or keto. Pts received keto 400 mg po tid and hydrocortisone 20 mg po qAM and 10 mg po qPM. GM-CSF 250 mcg/m2 was administered SQ on days 15–28 of each 28-day cycle. Results: Forty-two of 48 planned pts have been enrolled, 30 with clinical metastases, 12 with PSA-only disease and are evaluable for PSA response, using consensus criteria. The median age is 68 years (range: 53–84), and median PSA 23.1 ng/mL (range: 5.4–306.5). The median treatment duration is 5.1 months (range: 0.3–22+). Overall, 30 of 43 patients (69%) have experienced a ≥ 50% reduction in PSA. The PSA response proportion in the non-metastatic patients is 8/12 (66%) while the response proportion in those with metastases is 16/30 (53%, chi squared p = 0.41). Twenty-three patients have discontinued therapy after a median of three cycles. Progressive disease has occurred in 17 patients, 3 of 12 patients with non-metastatic disease and in 14 of 30 patients with metastatic disease (25% vs. 47%, chi squared p=0.20). Six patients have discontinued due to toxicity or patient choice. The primary endpoint of the study, overall time to progression, has not been reached at a median follow up of 7 months. Conclusions: There was no significant difference in response proportion and progressive disease rate in HRPC patients with and without metastatic disease treated with keto/GM-CSF. While these data require prospective confirmation in a larger group of patients, they suggest that secondary hormonal manipulations are warranted in either patient group.

No significant financial relationships to disclose.
Mutational profiling of protein kinases in prostate carcinoma
Authors: Andea A. , Osman I. , Scardino P. , Scher H. , Gerald W.
Published: March 2020

4636

Background: Protein kinases are important signal transduction mediators that play a critical role in malignant transformation. However, their involvement in prostate carcinogenesis has not been fully elucidated. Methods: In this pilot study, we sequenced the coding and exon-flanking intronic regions of selected protein kinases in 15 human prostate carcinoma specimens and 2 prostate cancer cell lines using standard techniques (Agencourt Biosciences). The 15 protein kinases genes included: tyrosine kinases (EGFR, EPHA3, EPHB2, ERBB2, FES, FGFR2, KDR, KIT, MET, NTRK1, NTRK2, NTRK3), tyrosine kinase-like (BRAF), serine/threonine kinase (AKT2), and the lipid kinase (PIK3CA). We also sequenced PTEN, p53 and AR because of their known association with prostate cancer and interactions with protein kinases. Results: We identified 452 different sites of single nucleotide sequence alterations and 50 insertion/deletion changes in multiple genes in the 17 specimens. The majority were intronic or involved untranslated regions (364 single nucleotide and all indels), and therefore were not further evaluated. Of the remaining 88 coding region alterations, 59 were synonymous and 10 were previously identified single nucleotide polymorphisms leaving 19 non-synonymous coding region changes (12 in 12 patient tumors and 9 in cell lines). Sequencing of corresponding non-neoplastic tissue revealed that 4 genes with sequence alterations were also altered in the germ-line and likely represent polymorphisms (EPHA3, KDR, NTRK1 and NTRK3). Six tumor specific mutation sites have been confirmed (one mutation is yet to be studied). Three represent unreported sites of mutation in prostate cancer involving MET (1 site) and EPHB2 (2 sites) and the others involved known sites within AR (1 site) and TP53 (2 sites). Conclusions: Our study successfully identified specific mutations of tyrosine kinases occurring in prostate cancer. Evaluation of a larger sample representing natural and treated history of prostate cancer to determine frequency and clinical associations, as well as functional studies to determine the biological significance of these mutations, is needed.

No significant financial relationships to disclose.
A modified CA-125 progression criterion in ovarian cancer (OC) patients (pts) receiving maintenance treatment following complete clinical response (cCR) to primary therapy
Authors: Liu P. , Moon J. , Alberts D. S. , Monk B. J. , Brady M. , Markman M.
Published: March 2020

5080

Background: CA-125 progression criterion for OC by Vergote et al (JNCI 2000; 92:1534) has been widely adopted, with 35 U/ml as the most commonly used normal limit. Based on recent findings (ASCO Proceedings 2005, #5013), primary therapy cCR OC pts with nadir CA-125 ≤10 versus >10–20 versus >20–35 have different prognosis. We propose to modify the CA-125 progression criterion in this setting as follows: for pts with nadir ≤10, value ≥20 that is confirmed equals progression; for pts with nadir >10, value ≥ 2×nadir that is confirmed equals progression. This new criterion essentially treats 10 U/ml as the normal limit. Methods: The proposed criterion combined with RECIST was tested on SWOG 9701/GOG 178 pts (n = 287) and compared to the existing criterion. All pts achieved cCR from primary therapy and entered the above maintenance trial with CA125 ≤35. Results: Of 91 pts last known to be progression-free by existing criterion, 10 (11%) new progressions were called. Available CA-125 values continued to rise in all except 1 case (1%). For 196 pts with known progressive disease, the progression date was unchanged by the new criterion in 42%, and was earlier by ≤60 days in 31%, 61–180 days in 16% and >180 days in 11% (overall median days early = 56). Conclusions: In a series of 39 primary therapy cCR pts with CA-125 ≤35, Santillan et al found a progressive low-level increase in CA-125 to be strongly predictive of disease recurrence (JCO 2005; 23:9338). Similarly, initial testing of the proposed CA-125 criterion demonstrated a low false positive rate and early detection of disease progression >2 months in approximately 30% of the same first line complete responders with progressive disease during or after maintenance treatment. Such pts can potentially benefit from starting alternative treatments early. The proposed criterion should be further investigated.

No significant financial relationships to disclose.
Concommitant boost: An effective regimen in locoregionally advanced head and neck cancers—A phase III randomised trial from a single institute in India
Authors: Sastri G. J. , Ghoshal S. , Kehwar T. S. , Sharma S. C.
Published: March 2020

5546

Background: The basic objective of this randomized trial was to test the efficacy of concomitant boost against standard fractionation in advanced head and neck cancers. Material and Methods: 285 patients with advanced head and neck cancers were randomized to receive either conventional radiotherapy 66 Gy/33 #/6.5 weeks or concomitant boost to a dose of 67.5 Gy/40 #/5 weeks. Results: The compliance to treatment was equal in both the arms.With a median follow up of 24 months, patients treated with concomitant boost had a significantly better two-year disease free survival and overall survival (p = 0.007 and p = 0.001respectively) than those treated by conventional fractionation. Grade III mucositis was seen in 35% patients in the concomitant boost arm and 19% in the conventional arm. On univariate analysis, the difference in outcome of oropharyngeal lesion p = 0.000, T3&T4 lesions (p = 0.004), Stage IV disease (p = 0.0005) and N+ disease (p = 0.000) were statistically significant in favour of concomitant boost arm. On multivariate analysis base of tongue site was an independent prognostic factor. Conclusions: Concomitant boost is an effective regimen in advanced head and neck cancers. In developing countries where 50–60% patients present at an advanced stage, this seems to be an optimal radiation therapy regimen especially in advanced oropharyngeal cancers.

No significant financial relationships to disclose.
Cancer patients’ attitudes toward future research uses of their donated tissue: Preliminary results of a mail survey study
Authors: Helft P. R. , Eckles R. E. , Kempf J. , Johnson-Calley C. S. , Brooks J. , Meslin E. M.
Published: March 2020

6009

Background: Millions of tissue samples are stored in the United States, but little is known about the attitudes of tissue donors. Understanding the attitudes of those who donate tissue for use in future research would inform the design of studies using stored tissues (ST). Methods: Eligible subjects included cancer patients who donated remaining tissue after biopsy or surgery to the Indiana University Cancer Center Tissue Bank. All subjects signed informed consent to donate tissue. A convenience sample were approached for participation. A survey instrument was developed from literature review and expert input, and refined by focus groups. Results: 243 surveys were mailed, and 196 completed surveys were returned (response rate 80.7%). Respondents were 70% married, 93% white, 54% female. 57% had completed at least some college. Average age was 60. Average time since diagnosis was 13.8 months. 81% of respondents remembered donating tissue. 61% were not at all or a little concerned about the privacy of their ST. >80% of subjects agreed that their ST could be used in future research on their type of cancer, other cancers, and other diseases,. Non-whites were less likely than whites to allow tissue to be used in research (p = 0.0128). Around 40% of respondents agreed that researchers should have to recontact them before using their ST. Non-whites and less educated subjects were more likely to want to be recontacted for each research use of their ST. 90% of subjects would allow their ST to be used by university researchers, but only 60% agreed that ST could be used by pharmaceutical companies. 39% objected to the use of STs to develop a treatment for profit. No differences were found in willingness of ST to be used in future research whether samples were identified, de-identified, or linked. 60% of respondents wanted to be notified of research results that would impact their, or their children’s, health whether treatments were available or not, and whether results had been validated or not. Conclusions: This cohort of cancer patients was very willing to allow their ST to be used in future research on all conditions, but a significant minority desired to be recontacted each time ST were used. These findings do not support policies based on a simple presumed consent model.

No significant financial relationships to disclose.
Correlates of patient referral to surgeons for treatment of breast cancer
Authors: Katz S. J. , Hofer T. P. , Hawley S. , Lantz P. M. , Janz N. K. , Schwartz K. , Liu L. , Deapen D. , Morrow M.
Published: March 2020

6032

Background: Characteristics of surgeons and their practice settings have been associated with cancer treatments and outcomes. Yet, there is little information about factors that are associated with referral pathways to surgeons and treatment settings. Methods: We merged and analyzed tumor registry and survey data from all women with DCIS and a 20% random sample of women with invasive breast cancer diagnosed in 2002 and reported to the Detroit and Los Angeles SEER registries (N = 1,844, response rate 77.4%,) and their surgeons (N = 365, response rate 80.0%). Results: About half of the patients (54.2%) reported that they were referred to their surgeon by another provider or health plan; 20.3% reported that they selected their surgeon; 21.9% reported that they both were referred and were involved in selecting their surgeon; and the remaining patients (4.9%) reported that they had a prior relationship with their surgeon primarily through previous surgery. Selecting their surgeon based on reputation was more frequently reported by white patients (36.5% vs 26.5%, p < .001), and more highly educated patients (40.0% and 21.6%, respectively for highest and lowest education categories, p < .001). Patients who selected their surgeon based on reputation were more likely to have received treatment from a high volume surgeon (adjusted odds ratio 2.3; 95% CI 1.7, 3.2) and more likely to have been treated in an American College of Surgeon approved cancer program or NCI-designated cancer center (adjusted odds ratio 1.8; 95% CI 1.1, 2.8; 3.0 95% CI 1.6, 5.3, respectively). Patients who were referred to their surgeon were less likely to be treated in an NCI-designated cancer center (adjusted OR 0.4; 95% CI 0.2, 0.8). Conclusions: Women with breast cancer who actively participate in the surgeon selection process are more likely to be treated by more experienced surgeons and in hospitals with approved cancer programs. Patients should be aware that provider or health plan-based referral may not connect them with the most experienced surgeon or comprehensive practice setting in their community. An active patient role in the surgeon selection process has important implications for both the type of treatment received and where care is delivered.

No significant financial relationships to disclose.
Economic evaluation of DVd versus VAd in the treatment of multiple myeloma: Results from a phase III multicenter randomized clinical trial
Authors: Rifkin R. M. , Hussein M. , Iskandar R. , O’Sullivan A. , Thompson D. , Forlenza J. , Fruchtman S. , Wildgust M. , McGarry L.
Published: March 2020

6050

Background: A randomized Phase III clinical trial of pegylated liposomal doxorubicin, vincristine, and reduced-dose dexamethasone (DVd) versus conventional doxorubicin, vincristine, and reduced-dose dexamethasone (VAd) found similar efficacy in the treatment of newly-diagnosed multiple myeloma (Cancer, in press). However, observed clinical advantages of DVd included less toxicity and supportive care. (Cancer In press). Methods: This economic evaluation was conducted as a piggyback to the clinical trial. Utilization data were collected prospectively for enrolled patients (DVd = 97; VAd = 95). Costs were estimated by applying standard US unit costs in 2004 to observed utilization. We compared resource utilization and costs for study drug administration, other care (hospitalizations due to AEs, tests, transfusions, and concomitant medications), and total costs during follow-up for patients receiving DVd versus VAd using 2-sided t-tests. Results: DVd patients required significantly fewer hospital (1.5 vs 8.5; p < 0.01) and clinic days (4.8 vs 14.4; p < 0.01) for study drug administration. Costs of study drug were significantly higher for DVd patients ($16,181 vs $788; p < 0.01), but lower hospitalization costs ($3,311 vs $18,492; p < 0.01) and clinic costs ($797 vs $2,412; p < 0.01) for drug administration more than offset these costs, resulting in nominally lower overall study drug administration costs for DVd versus VAd ($20,289 vs $21,692; p = 0.64). No other component of care differed significantly between the two groups (costs of other care: $14,152 for DVd vs $14,154 for VAd; p = 0.99) and overall treatment costs ($34,442 for DVd vs $35,846 for VAd; p = 0.76) were similar in the two groups. DVd patients had approximately 10 additional days of follow-up over the trial period (149.4 vs 139.2) versus VAd patients. Conclusions: Despite higher drug acquisition costs, use of DVd did not increase the overall cost of treatment compared to VAd.

[Table: see text]
Cost-effectiveness of influenza vaccination of adult cancer patients
Authors: Avritscher E. B. , Cooksley C. D. , Geraci J. M. , Bekele B. N. , Cantor S. B. , Rolston K. V. , Elting L. S.
Published: March 2020

6079

Background: Despite recommendations to immunize all patients at increased risk from underlying immunosuppressive disease against influenza, many insurance plans do not cover the vaccine. We analyzed the cost-effectiveness of vaccinating adult cancer patients against influenza from the perspective of a third-party payer. Methods: We developed a decision-analytic model using epidemiological, vaccine effectiveness, resource utilization, cost, and utility data from published sources, supplemented with data collected from our institutional accounting system. Two strategies were compared: vaccination of adult cancer patients against influenza, and no vaccination. The cost-effectiveness analysis included charges (inflated to 2005 US$) for vaccination, influenza-related hospitalizations, physician and emergency visits, and the average wholesale price for prescription drugs and influenza vaccine. The base-case patient for the model was assumed to be a 67-year-old cancer patient (the median age at initial cancer diagnosis - all sites - for the 1998–2002 SEER population) with active disease. Results: The effectiveness of the no vaccination strategy was 4.665 QALYs at a cost of $95.23. The effectiveness of the influenza vaccine was 4.672 QALYs at a cost of $70.73. Thus, the vaccination strategy provided an incremental effectiveness of 0.007 QALYs over the no vaccination strategy at a reduction in cost of $24.50. Based on these gains, we estimate that vaccination of all adult cancer patients could potentially save third-party payers over $87 million in addition to gains in clinical benefits. The model was not sensitive to plausible changes in cancer survival, incidence of influenza, vaccine effectiveness, vaccine price, and risk of influenza-related hospitalization. Conclusions: Influenza vaccine is cost-effective for adult cancer patients. Health plans should expand their coverage to include the vaccine for adult patients with cancer.

No significant financial relationships to disclose.
Association of low P27 with loss of hormone receptors in small (T1a/b) breast cancers
Authors: Wu J. , Mirchandani D. , Smith J. A. , Inghirami G. , Roses D. , Zeleniuch-Jacquotte A. , Muggia F.
Published: March 2020

624

Background: P27kip1 is a nuclear protein that controls the cell cycle by inhibiting cyclin dependent kinases. In breast cancer cell lines, both estrogen and her-2/neu degrade p27 through the ubiquitin-proteasome pathway. T1N0M0 breast cancers with high p27 expression have excellent long-term survival (Loda et al, Cancer Research 1998), now we examine the association of low p27 and other prognostic factors in these patients. Methods: 122 T1N0M0 infiltrating ductal carcinoma were examined using immunohistochemistry. Specific monoclonal antibodies were used against estrogen receptor (ER), progesterone receptor (PR), Her-2/neu, p53 and p27. Percentage of cells stained were considered negative (or low for p27) if: ER <10%, PR <10%, p53<40%, her-2/neu DAKO score ≤ 1+, p27 (nuclear stain) <50%. Results: In T1a/bN0M0 tumors, 4/5 (80%) of low p27 tumors were also hormone receptor negative, while only 5/63 (8%) of the high p27 tumors were hormone receptor negative (P< 0.001, Fisher’s exact test). Although T1cN0M0 tumors showed a similar trend [4/12 (33%) of low p27 vs. 7/42 (17%) of high p27 tumors were hormone receptor negative], the difference was not statistically significant. No correlation was seen between low p27, her-2/neu, or p53 mutation. Conclusion: There is an association of low p27 and loss of hormone receptors in T1a/bN0M0 breast cancers, which may identify a subset of patients with a worse prognosis. Exploring the causes of p27 dysregulation (e.g., ubiquitin ligase overexpression) may shed further light on the significance of these associations.

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No significant financial relationships to disclose.
Correlation of CA15.3 levels with clinical response in advanced breast cancer (ABC) patients receiving fulvestrant
Authors: Robertson J. F. , Agrawal A. , Gutteridge E. , Cheung K. , Evans A. J.
Published: March 2020

641

Background: A transient initial rise (i.e. spike) in CA15.3 has been reported during treatment with anti-cancer therapies such as tamoxifen and chemotherapy. The spike may result from the partial agonistic and cytotoxic effects of these agents, respectively. Here, we report the clinical relevance of a transient initial rise in CA15.3 in patients treated with fulvestrant, an estrogen receptor (ER) antagonist with no agonist effects. Methods: Serial measurements of CA15.3 were made at regular intervals to monitor response in patients receiving fulvestrant 250 mg/month for the treatment of ABC. Marker profile at baseline, after 1, 3, 6, 9, and 12 months of treatment and at the time of progression was correlated with clinical benefit (CB) (complete response [CR]/partial response [PR]/stable disease ≥6 months) as per UICC criteria. Results: Sixty-seven patients (41 with metastatic breast cancer [MBC]; 26 with locally advanced primary breast cancer [LAPC]) with a median age of 72.9 years were treated with fulvestrant. CB was observed in 64.2% (n=43) with objective response (OR) in 19.4% (n=13). Median duration of clinical benefit (DoCB) was 26.6+ months. CA15.3 data at month 1 were available for 33 patients with CB. Eleven patients with CB (33.3%) had a rise in CA15.3 at month 1. Comparative responses in patients with and without spike phenomenon are shown in the Table . Five MBC patients with a spike in CA15.3 had an OR (CR=1; PR=4) compared with none of the MBC patients without a spike. Conclusions: Spike phenomenon is observed in more patients with MBC than patients with LAPC, which may reflect the overall tumor load in MBC patients. Higher OR rates were observed in MBC patients with spike phenomenon, but shorter DoCB. There was no apparent difference in ER status between patients with or without spike. Fulvestrant should not be stopped during the initial 1–2 months of treatment solely on the basis of a rising tumor marker, as a spike is observed in one-third of ABC patients who achieve CB with fulvestrant.

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K562/GM-CSF vaccination reduces tumor burden, including achieving molecular remissions, in chronic myeloid leukemia (CML) patients (PTS) with residual disease on imatinib mesylate (IM)
Authors: Smith B. , Kasamon Y. L. , Miller C. B. , Chia C. , Gocke C. , Kowalski J. , Tartakovsky I. , Biedrzycki B. , Jones R. J. , Hege K. , Levitsky H. I.
Published: March 2020

6509

Background: Despite high rates of clinical responses to IM, molecular complete responses are rare. The curative potential of allo transplantation and donor lymphocyte infusions underscores CML’s responsiveness to T cell mediated immunity. K562/GM-CSF is a tumor vaccine derived from a CML cell line that expresses several defined CML associated antigens and has been genetically engineered to produce GM-CSF. A pilot vaccination strategy was developed to determine if K562/GM-CSF immunotherapy in combination with IM could enhance T cell reactivity and clinical responses in pts having persistent, measurable disease despite 1 or more years on IM. Methods: Eligibility required pts to have achieved a major cytogenetic response (<35% Ph+ cells) while on a stable dose of IM. Disease burden was measured serially over 12 wks prior to vaccines. 4 vaccines were administered in 3 wk intervals, each consisting of 1 × 108 irradiated K562/GM-CSF cells distributed over 10 sites, with or without topical 5% Aldara (a Toll-like receptor 7 agonist) used as a vaccine adjuvant. Disease burden was measured at 6 wk intervals for 9 mos from the first vaccine and specimens were banked for measurement of immune responses. Results: The trial enrolled 19 pts, all have completed the planned 4 vaccinations and 14 pts have completed all planned disease burden measurements. The median age is 52 (range 28–76) yrs with a median time from dx to enrollment of 57 (range 16–111) mos. Pts were on IM for a median of 37 (13–53) mos prior. 4 of 19 pts had FISH pos as their best previous response (BPR) with 2 becoming FISH neg post-vaccine (1 became PCR neg and 1 achieved a >1 log reduction in disease burden by PCR). Of the 15 pts whose BPR was FISH neg/PCR pos, 4 are now PCR neg post vaccine, 4 experienced a >1 log and 1 had 0.5–0.99 log reduction by PCR. Mean PCR levels for the 19 pts declined btwn pre- and post-vaccine measures (p=0.01). 3 of 5 pts achieving PCR neg remain so beyond 6 months. Only 1 pt progressed having entered the study with a heavy disease burden (30% FISH pos). Conclusions: K562/GM-CSF vaccine appears to improve responses in pts on IM, including achieving complete molecular remissions, despite long durations of previous IM therapy.

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Nonmyeloablative hematopoietic cell transplantation (HCT) for treatment of patients (pts) with fludarabine-refractory chronic lymphocytic leukemia (CLL) results in prolonged median survival
Authors: Sorror M. , Sandmaier B. , Maris M. , Storer B. , Radich J. , Agura E. , Niederwieser D. , Blume K. , Storb R. , Maloney D.
Published: March 2020

6520

Background: Pts with fludarabine-refractory CLL have a poor prognosis with median survival of 12 months. A phase II trial of Campath resulted in median survival of 16 months. Curative alternatives are required. Methods: We previously reported 2-year overall survival (OS) of 60% for 64 pts treated with nonmyeloablative HCT from related (n=44) or unrelated (n=20) donors (Sorror. JCO, 2005). Those pts were refractory to fludarabine (88%) ± additional agents. Eligibility criteria, conditioning and immunosuppression regimens, and primary endpoint were previously described. Here, we extended the follow up to 38 (range: 10–74) months after HCT ( Table ). Results: Chronic extensive graft-versus-host disease (GVHD) at 3 years was 53% and non-relapse mortality (NRM) was 27%. Among 30 pts who achieved initial responses {25 complete (CR) and 5 partial (PR)}, one patient died while in CR from NRM, one patient with PR progressed, while remaining 28 pts continued alive and in remission. CR and relapse rate at 3 years were 54% and 32%, respectively. Unrelated recipients had a significantly higher CR rate than related recipients. Ten responding pts were tested for molecular eradication of their disease and all were negative at a median of 52 months. There were 6 deaths in this extended follow up, 5 from relapse/progression and one from pneumonia. Overall, 33 pts are alive; 24 in CR, 4 in PR, 2 with stable disease, and 3 with relapse/progression. Estimated 3-year rates of OS, disease-free survival (DFS), and NRM were 54%, 42%, and 27% respectively. In multivariate analysis, high pretransplant comorbidity scores predicted higher NRM and worse OS while bulky lymphadenopathy predicted increased risk of progression. Conclusion: Nonmyeloablative HCT resulted in an extended median survival of greater than 3 years for pts with fludarabine-refractory CLL. The use of unrelated grafts was associated with a trend toward better DFS.

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No significant financial relationships to disclose.
Treatment of patients (pts) with chronic myeloid leukemia (CML) and imatinib failure after developing BCR-ABL kinase mutations with allogeneic stem cell transplantation (ASCT)
Authors: Champlin R. E. , Jabbour E. , Cortes J. , Kantarjian H. , Andersson B. S. , Giralt S. , De Lima M.
Published: March 2020

6545

Background: ASCT is curative for many pts with CML, and may be effective after imatinib failure. Resistance to imatinib is most often associated with point mutations in the Bcr-Abl kinase domain. The outcome of pts with Bcr-Abl kinase mutations after ASCT is not known. Methods: We assessed the outcome of ASCT in 10 pts with CML (chronic phase [CP]=3, accelerated phase [AP]=4, blast phase [BP]=3) harboring 9 different protein kinase mutations. P-loop mutations were detected in 5 (50%) pts; the most common type of mutation was T315I detected in 2 pts (one AP and one CP). At the time of ASCT, one pt was in major molecular remission (MMR) (BP, Q252H), one was in major cytogenetic response (CP, T315I), and 2 were in complete hematologic response (2 BP, Y253H and E255K). Preparative regimen was busulfan based regimen in 7 and fludarabine + melphalan in 3 pts. Eight male and 2 female pts, median age of 44 years (range, 26–63 years), received their ASCT between July 2002 and October 2005. Donor was fully matched related in 5 (50%) and unrelated in 5 (50%) pts. Source of stem cells was peripheral blood and bone marrow in 3 and 7 pts, respectively. Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus and mini methotrexate. Results: All patients engrafted; there was no treatment-related mortality. Chimerism studies at day 30 and 100 post ASCT were available in 9 pts and were 100% of donor type in all but one. Nine pts responded: 7 achieved a complete molecular remission (CMR) and 2 achieved a MMR. Two (22%) pts (Q252H [BP] and T315I [AP]) relapsed and died of disease progression after a median of 9 months. All the remaining 7 pts were in CMR for a median of 17 months (range, 3–22+ months). Conclusions: ASCT is an important salvage option for pts who develop resistance to imatinib through Bcr-Abl mutations. Early introduction of such strategy may result in better outcome.

No significant financial relationships to disclose.
Autologous or allogeneic stem cell transplantation versus chemotherapy in acute myeloid leukemia and subgroups: A multicenter trial by the German AML Cooperative Group
Authors: Buchner T. , Berdel W. E. , Kienast J. , Kolb H. , Staib P. , Reichle A. , Schoch C. , Haferlach T. , Sauerland M. C. , Hiddemann W.
Published: March 2020

6556

Background: From the data available the role of autologous and allogeneic stem cell transplantation (auto/allo SCT) versus post-remission chemotherapy appears uncertain and is readdressed in the present trial. Methods: Pts were stratified for cytogenetic groups, de-novo/secondary AML, LDH, WBC, and were up-front randomized in one step to induction by HAM-HAM vs TAD-HAM, and to G-CSF priming vs. no G-CSF. These two randomizations did not result in different outcome. Pts were also upfront randomized to auto SCT vs monthly maintenance chemotherapy. Within the two randomized arms pts with histocompatible family donors underwent priority allo SCT. Results: Since 1999 840 pts 16–60 y of age entered the trial. 14%, 62%, 21%, and 3% of pts had favorable, intermediate, unfavorable and unknown karyotype, and 19% had secondary AML. 70% of pts went into complete remission (CR). The probability of overall survival (OS) at 3 years in the auto SCT and the maintenance arm is 43% vs 41% (p=0.52), the relapse-free survival (RFS) is 40% vs 40% (p=0.78), and the ongoing remission duration (RD) is 48% vs 46% (p=0.65). Among pts alive and in CR 73% did receive auto SCT or maintenance or allo SCT, similar to previous trials (NEJM 332:217,1995, Blood 90:2978,1997, Lancet 351:700,1998, NEJM 339:1649,1998). The outcome according to therapy given in the auto SCT arm and the maintenance arm shows ongoing RD of 44% vs 50% (p=0.31), RFS of 44% vs 48% (p=0.35), and OS of 53% vs 69% (p=0.005). 128 pts underwent allo SCT. In a matched pair analysis with concordance of pairs in karyotype, de-novo/secondary AML, induction chemotherapy, and RFS at the time of SCT, RD shows a superiority of allo SCT (p<0.001), while OS is similar between the two arms (p=0.65). No prognostic subgroup with a special benefit from auto or allo SCT can be identified so far. Conclusions: Among current alternative strategies only novel approaches in allo SCT reducing the high transplant related death rate may further improve the cure of pts with AML and subgroups.

No significant financial relationships to disclose.