tbuckley/cabot-search huggingface dataset:
Nonsurgical management of esophageal cancer: report of a study of combined radiotherapy and chemotherapy.
Authors: L R Coia, P F Engstrom, A Paul
Journal: Journal of Clinical Oncology (1987)

Between October 1980 and December 1985, 50 patients with esophageal cancer were treated with combined radiotherapy and chemotherapy (5-fluorouracil [5-FU] and mitomycin C). Thirty patients with stage I or II disease received definitive treatment consisting of 6,000 cGy in 6 to 7 weeks and 5-FU (1,000 mg/m2/24 h) as a continuous intravenous (IV) infusion for 96 hours, starting on days 2 and 29. Mitomycin C (10 mg/m2) was administered as a bolus injection on day 2. Twenty patients received palliative treatment (5,000 cGy plus chemotherapy) for stage III or IV disease (extraesophageal spread or distant metastases). All patients treated in this program had an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2. Of the 30 definitively treated patients, 23 had squamous cell cancer, while seven had adenocarcinoma. Follow-up ranged from 6 months to 63 months. The complete response rate at 1 to 3 months following completion of treatment was 87% (26 of 30) documented by barium swallow and endoscopy (+/- biopsy). The actuarially determined local relapse-free rate at 1 year and beyond was 73%, and the actuarial survivals at 1, 2, and 5 years were 68%, 47%, and 32%, respectively. Of the 20 palliatively treated patients, ten had squamous cell carcinoma, eight had adenocarcinoma, and two had undifferentiated carcinoma. Seventeen patients were evaluable for freedom from dysphagia 1 or more months following completion of treatment. Eighty-two percent of evaluable patients (14 of 17) had no dysphagia posttreatment, while 64% (11 of 17) remained free of dysphagia until death or last follow-up, emphasizing the significant local control of those patients. The median survival for this group was 8 months. Treatment was well tolerated, and acute toxicity included esophagitis, stomatitis, oral candidiasis, and hematologic toxicities of thrombocytopenia and neutropenia. Late toxicities were predominantly manifested as a mild to moderate benign stricture, which required dilatation in four patients. One patient developed a perforation into the mediastinum in the absence of tumor, while two patients with persistent local disease developed tracheoesophageal fistula, and radiation pneumonitis was observed in two patients. This combination of radiation therapy with infusional 5-FU and mitomycin C is an effective and relatively well-tolerated regimen in the treatment of esophageal cancer. Surgical resection may not be necessary when high-dose radiation and chemotherapy are used.
Phase II study of amonafide: results of treatment and lessons learned from the study of an investigational agent in previously untreated patients with extensive small-cell lung cancer.
Authors: W K Evans, E A Eisenhauer, Y Cormier, J Ayoub, R Wierzbicki, F Laberge, F A Shepherd
Journal: Journal of Clinical Oncology (1990)

Thirteen previously untreated patients with extensive small-cell lung cancer (SCLC) were treated with the investigational agent amonafide in a dose of 300 mg/m2 intravenously (IV) over 1 hour daily for 5 consecutive days. No responses were seen in 12 eligible patients. Myelosuppression was only occasionally seen. Other toxicities included diaphoresis, chest pain, local irritation at the injection site, arthralgias, nausea and vomiting, and neuromuscular problems. There were two early deaths, both attributable to tumor progression with resultant obstruction of a vital structure. Ten patients crossed over to alternate active therapy (etoposide [VP-16]-cisplatin) and five responded. The median survival time (MST) of the whole group of treated patients was 31 weeks. In future trials of investigational new drugs in previously untreated SCLC, we recommend that patients with the following characteristics be excluded: Eastern Cooperative Oncology Group (ECOG) performance status 2, 3, and 4; superior vena cava (SVC) obstruction; any major paraneoplastic syndrome; serious comorbid illness; and extensive hepatic involvement by tumor. The trial design should include prompt crossover to active alternative therapy, such as VP-16 and cisplatin, for disease progression or for failure to respond after two treatment cycles. Also, the trial design should use an early stopping rule based on interest in identifying only very active agents with a minimum response rate of 30%.
Phase II study of verubulin (MPC-6827) for the treatment of subjects with recurrent glioblastoma naïve to treatment with bevacizumab.
Authors: L. J. Kim, M. C. Chamberlain, J. Zhu, J. J. Raizer, S. A. Grimm, S. Phuphanich, C. E. Fadul, S. Rosenfeld, A. H. Balch, C. C. Pope, M. Brulotte, A. A. P. Beelen, L. D. Recht
Journal: Journal of Clinical Oncology (2011)

2088 Background: Treatment options are limited for recurrent glioblastoma (GBM). Verubulin is a microtubule destabilizer and vascular disrupting agent that achieves high brain concentration relative to plasma in animals. Methods: Adults with recurrent GBM who failed prior standard therapy were eligible. The primary endpoint was 6-month progression-free survival (PFS-6). Eligible subjects had a KPS ≥ 60, were free of active cardiovascular disease and uncontrolled hypertension and had no prior treatment with angiogenic inhibitors. Verubulin was administered at 3.3mg/m2as a 2-hour IV infusion once weekly for 3 consecutive weeks in a 4-week cycle. Response was assessed using the Macdonald criteria. The planned sample size was thirty-four subjects. Results: 31 adults were treated (20 men; 11 women). All subjects had prior tumor resection, a median of two chemotherapies (up-front with RT and salvage); the majority were in first relapse (77%). Median age and KPS were 56 years (range 23-74) and 90 (range 70-100), respectively. Median number of verubulin cycles completed was 2 (range 0-12); one subject remains on treatment. The most common adverse events were fatigue (19%), nausea (10%) and constipation (6%). One subject discontinued the study due to a grade 2 ventricular arrhythmia. Another subject with significant cardiovascular risk factors had a non-fatal myocardial infarction. 3 subjects (10%) did not complete at least 2 cycles of treatment and were not evaluated for disease response. The PFS-6 was 14% (4/28) [90% CI: 3%, 25%] with a median PFS time of 1.8 months [90%CI: 1.8, 1.9], a mean PFS time of 2.6 months [range 0.8-11.9], a median overall survival of 9.9 months [90%CI: 8.3, 11.6] and a mean overall survival of 6.7 months [range 1.1-15.9]. Best overall response by Macdonald criteria was partial response (n=3; 10%) and stable disease (n=7; 23%). Median duration of stable disease was 3.9 months [90% CI: 3.8, 4.0]. Conclusions: Single agent verubulin, in this dose and schedule, in adults with recurrent GBM is well tolerated and associated with acceptable toxicity, and appears to have modest activity.
A phase I study of sequential administration of S-1 and cisplatin (CDDP) for patients with metastatic gastric cancer (MGC)
Authors: E. Baba, H. Fujishima, H. Kusaba, T. Esaki, H. Ariyama, K. Kato, R. Tanaka, S. Nakano, M. Harada
Journal: Journal of Clinical Oncology (2006)

14101 Background: The combination of 5-FU and CDDP has been reported to be active against metastatic gastric cancer (MGC), and great synergy has been shown in vivo and in vitro when 5-FU precedes CDDP. We investigated a sequential combination of S-1 (Tegafur, oxonic acid, CDHP) followed by CDDP for MGC. Methods: In order to determine a maximum tolerated dose (MTD) and recommended phase II dose (RD), we conducted a phase I trial applying increasing doses of oral administration of S-1 (65–80mg/m 2 ) for 21 days and increasing doses of CDDP (60–80mg/m 2 ) on day 22 every 35 days. Pts with metastatic or recurrent gastric cancer, no prior chemotherapy, measurable disease, performance status ECOG less than 3, and adequate organ functions were eligible for the study. Three pts were treated at each dose level with escalation based on toxicity. Fifteen pts were included and evaluated for DLT and MTD. Results: DLT was NCICTC grade 3 anorexia and fatigue in patients treated at the dose level 5 of S-1 80mg/m 2 and CDDP 80mg/m 2 . Other toxicity more than grade 3 was neutropenia (grade 3) and nausea/vomiting (grade 3). Non-hematological toxicities were grade 1/2 and included diarrhea, nausea and stomatitis. There was no treatment-related mortality. The recommended dose was a combination of S-1 80mg/m 2 and CDDP 70mg/m 2 . A tentative median survival was 19.5 months. Conclusions: This sequential S-1 and CDDP administered every 35 days is tolerable and beneficial for patients with MGC, and thus the consequent phase II trial is recommended. A multicenter phase II study is currently under way. No significant financial relationships to disclose.
Toddler deaths resulting from ingestion of iron supplements--Los Angeles, 1992-1993
Authors: Billie P. Weiss, A. Alkon, Alexander Kelter
Journal: MMWR Morbidity and Mortality Weekly Report (1993)

During June 1992-January 1993, five children aged 11-18 months in the Los Angeles area died after ingesting iron supplement tablets. The first death was reported by the Consumer Product Safety Commission (CPSC) to the Los Angeles County Department of Health Services (LADHS) in November 1992 and then reviewed by the Los Angeles County Child Death Review Committee. On January 6, the Los Angeles County coroner's office reported three additional deaths associated with ingestion of iron to the Child Death Review Committee and the health department. A fifth death resulting from iron poisoning was reported January 29. This report summarizes preliminary information from an investigation of these cases. Language: en
Excision of 13 phyllodes bilateral breast tumors in one patient
Authors: J. L. Marti, K. Hiotis
Journal: Journal of Clinical Oncology (2008)

11584 Background: Phyllodes tumors are rare fibroepithelial breast tumors, classified as benign, borderline, or malignant. The prognosis is favorable, with a local recurrence rate of 15% and distant recurrence of 5–10%. Phyllodes tumors require wide excision with negative margins to prevent recurrence. We report a case of multiple bilateral tumors in one patient, an occurrence not yet reported in the world literature. Methods: The medical records of a patient diagnosed with multiple bilateral phyllodes tumors and fibroadenomas of the breast were reviewed. Results: A 16-year old girl reported the presence of palpable bilateral breast masses over the past few years. An initial ultrasound at age 14 revealed “indeterminate” solid masses. Her family history was significant for a grandmother with premenopausal breast cancer. On exam, she had multiple masses palpable bilaterally, with the largest masses of the right breast measuring 8 cm and 5 cm. The largest mass on the left was approximately 9 cm. No lymphadenopathy was present. Ultrasound revealed multiple masses bilaterally, some increased in size, with many suspicious for malignancy, with a BI-RADS score of 4b. Mammography revealed multiple bilateral masses, with many suspicious for cancer. A core biopsy of a left breast mass revealed a possible fibroadenoma, while core biopsy of the right suggested giant juvenile fibroadenoma versus low-grade phyllodes tumor. The patient underwent bilateral excision of multiple breast masses with breast reduction. Final pathology confirmed 15 right breast masses. The dominant mass on the right was a low-grade phyllodes tumor. The other masses consisted of a low-grade phyllodes tumor, 8 benign phyllodes tumors, and 5 fibroadenomas. On the left, 12 breast masses were excised: 3 benign phyllodes tumors, 8 fibroadenomas, and 1 complex fibroadenoma. Conclusions: To our knowledge, we present the first reported case of multiple, bilateral phyllodes breast tumors in an adolescent girl. Multiple bilateral breast masses in a young patient do not always represent benign fibroadenomas or fibrocystic disease. Young patients with multiple bilateral breast masses should receive a thorough evaluation to rule out malignancy. No significant financial relationships to disclose.
Testicular ultrasound (TU) screening in men from familial testicular cancer (FTC) kindreds
Authors: L. A. Korde, A. Premkumar, J. L. Kramer, W. Linehan, S. Pfeiffer, G. Bratslavsky, M. H. Greene
Journal: Journal of Clinical Oncology (2006)

14547 Background: A family history of testicular cancer (TC) is associated with a 2- to 10-fold increase in TC risk. Specific abnormalities of the urogenital tract (e.g., cryptorchidism, inguinal hernia) also increase risk. The association between testicular microlithiasis (TM) and testicular intraepithelial neoplasia (TIN) has suggested that the former may be a TC risk factor. The finding of inhomogenous echotexture on ultrasound has also been associated with an increased risk of TIN. In this study, we evaluate ultrasongraphic abnormalities in men with a history of TC and their kindreds. Methods: We analyzed testicular ultrasounds (TU) from 45 FTC cases and 35 unaffected male relatives, drawn from 31 multiple-case FTC families. TU were performed between January 2003 and November 2005 as part of an NCI multidisciplinary etiologic study of FTC. All studies were reviewed by a single radiologist. Results: We found no incident TC. Five focal lesions were seen. Three were thought to be cysts and 2 required further follow-up. The frequency of varicocele and epididymal cyst was similar in both groups. Hydrocele was seen in 7 (16%) cases and 3 (9%) unaffecteds (OR = 2.0; 95% CI = 0.5–8.3). Inhomogenous testicular parenchyma was noted in 12 (27%) cases and 3 (9%) unaffected family members (OR = 3.9; 95% CI = 1.0–15.0). TM was seen in 20 subjects [15 (34%) cases and 5 (14%) unaffecteds, OR = 3.1; 95% CI = 1.0–9.6]. An additional 10 subjects (7 cases, 3 unaffecteds) had calcifications that did not meet diagnostic criteria for TM. The finding of TM was confined to 13 of the 31 families. In 6 of these 13 families, 2 or more subjects had TM. Conclusion: A number of genitourinary conditions were more common in FTC cases than in unaffected blood relatives, providing support for the testicular dysgenesis hypothesis related to TC etiology. TM was found in a high proportion of cases and in a smaller proportion of unaffecteds. In this small series, TM appeared to cluster in families. If validated, these findings could have important implications for both screening and follow-up of FTC families. No significant financial relationships to disclose.
On the Epizootiology of the Lactic Dehydrogenase Agent&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Charles G. Crispens, Jr.
Journal: JNCI Journal of the National Cancer Institute (1964)

The lactic dehydrogenase (LDH) agent was in saliva and urine from mice at 36 hours, but not at 5 weeks, after infection. In feces, excretion of this “virus” was demonstrable in tumor-bearing mice and infected animals, the latter as early as 36 hours and as late as 105 days after inoculation. These findings and the demonstration that fecal material is infectious, even after 96 hours at room temperature, suggest that feces may be important in transmission of the LDH agent between mice in the same cage. Transmission of the LDH agent was not observed between animals in different cages. No evidence indicated that it is transmitted in the semen of infected males, and in utero or in the milk of females infected before pregnancy. These observations suggest that most mouse colonies should be free from the LDH agent. However, inadequate cleaning of cages or handling of animals might result in the spread of this “virus” to normal mice.
Study of 19 patients (pts) with large-cell neuroendocrine tumors of the lung.
Authors: M. M. Vaslamatzis, G. Papaxoinis, P. Karra, N. Alevizopoulos, C. Vamvouka, E. Patila, E. Ballis, E. Testempassi, C. Zoublios, E. Ntouvelis
Journal: Journal of Clinical Oncology (2010)

e18138 Background: The term large cell neuroendocrine carcinomas (LCNEC) includes lung tumors with neuroendocrine phenotype, but do not meet the criteria for the carcinoid, atypical carcinoid and SCLC. Methods: The aim of the study was to present clinicopathological characteristics and treatment results of LCNEC pts. Results: In our Dept 19 LCNEC pts (m/f = 17/2, 1/1996-1/2010), were consecutively treated. All histological specimens were reviewed. Cough ± haemoptysis ± fever, cervical lymphadenopathy, bone pain, SVC syndrome, chest pain, epilepsy, paraneoplastic tetraplegy or myopathy were the most common presenting symptoms in 5, 3, 3, 2, 1, 1, 1, and 1 pts, respectively. Two pts were asymptomatic. Pure LCNEC was diagnosed in 13, mixed LCNEC-SCLC in 3 and LCNEC-adenoCa in 3 pts. Six pts had stage (st) I-IIIA and 13 st IIIB+IV. Diagnosis was done by curative surgery in 6 or by lymph node biopsy, FNA and during bronchoscopy in 5, 4 and 4 pts, respectively. Four pts (st I-IIIA) were only followed-up (f-u), while 15 received chemotherapy (CTP) consisted of CDDP+VP16 in 8, CAVE in 6 and CDDP + pemetrexed in 1. Two pts (st I and IIIA) were disease free 22 and 80 mo post-surgery vs those treated with CTP who had m PFS 2.5 mo and m OS 6 mo. The m PFS was 16 and 2.5 mo (p = 0.006) and the m OS was 24 and 6 mo (p = 0.003) for st ≤ IIIA and > IIIA respectively. All neoplasms had neuroendocrine morphology, extensive necrosis, atypical mitosis and stained CD 56, synaptophysin and chromogranin (++/+++). Specimens from 8 pts were stained for TopoIIa and ERCC1. All pts expressed TopoIIa (m expression 40% of cells) and only 3 ERCC1 (10%-90%). TopoIIa expression seemed to be positively correlated with ERCC1 (Spearman's Rho = 0.873, p = 0.005), although specimen number was low. M expression of TopoIIa in st I-IIIA pts was 25% (10-60%) vs 65% (35-80%) in IIIB+IV. ERCC1 was expressed in 1/5 pts (10% of cells) with st ≤ IIIA and in 2/3 pts (40-90%) with metastases. The pt with st IV and ERCC1 (-) is progression-free after 16 mo, time much longer than that achieved by the rest of st IV pts. Conclusions: In our study, metastatic LCNEC pts had poor prognosis and chemorefractory disease while those with operable disease had better outcome. TopoIIa and ERCC1 expression seems to be consistent with this difference in biological behavior. No significant financial relationships to disclose.
Analysis of risk factors predicting time to development of brain metastases
Authors: M. Knauer, A. Rottenfusser, R. Bartsch, K. Dieckmann, C. Wenzel, S. Fromm, H. Eiter, G. G. Steger, C. C. Zielinski, A. de Vries
Journal: Journal of Clinical Oncology (2008)

1076 Background: Since the introduction of trastuzumab (T), different groups reported an increased incidence of brain metastases (BM) in patients (pts) with HER2-positive breast cancer (BC), although one centre published contradicting results. Usually, this is attributed to prolonged survival, in association with the inability of antibodies to pass the blood-brain-barrier. Furthermore, based on preclinical data, it was suggested that HER2-positive BC had an increased affinity to brain tissue. We investigated which factors were potentially associated with shorter time to development of BM. Methods: One hundred ninety-four pts with BM from BC were identified at two Austrian centres. All received whole brain radiotherapy (WBRT) of 30 Gy with or without boost irradiation or surgical resection. All pt data concerning epidemiology, histology, and outcome is available. A multivariate analysis (Cox regression) was performed to identify factors (age, grading, ER/PgR-status, HER2-status, tumour stage at diagnosis, lung metastases, liver metastases, T before diagnosis of BM) significantly associated with shorter time to development of BM. Results: Median age was 55 years (y), range 28 - 81 y, and time to development of BM was 29 months (m), range 2 - 254 m, 95% CI 22.97–35.03. Overall survival following WBRT was 7 m, range 1 - 83 m, 95% CI 5.08–8.92. The following factors predicted shorter time to development of BM: negative endocrine receptor status (p=0.026), HER2-positive disease (p=0.003), stage IV disease at first presentation (p<0.001), and lung metastases (p=0.043). Conclusions: Risk factors associated with increased incidence of BM have been described: ER/PgR-negative, HER2-positive disease, high grade, and lung metastases. Some groups reported an increase in pts on T. Our data show that HER2-positive BC is significantly associated with shorter time to development of BM, while no influence of T treatment was observed. These results underline preclinical data suggesting a higher affinity of HER2-positive BC to the brain. T, on the other hand, had no prophylactic effect. Therefore, trials evaluating the combination of T with substances able to penetrate into the brain are warranted in this population. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Amgen, Pfizer, sanofi-aventis Amgen
Effect of anti-CD19 BiTE blinatumomab on complete remission rate and overall survival in adult patients with relapsed/refractory B-precursor ALL.
Authors: Max Topp, Nicola Goekbuget, Gerhard Zugmaier, Andreas Viardot, Matthias Stelljes, Svenja Neumann, Heinz-August Horst, Albrecht Reichle, Reinhard Marks, Brueggemann Monika, Matthias Ritgen, Petra Klappers, Noemi Mergen, Marie-Elisabeth Goebeler, Hermann Einsele, Dieter Hoelzer, Ralph Bargou
Journal: Journal of Clinical Oncology (2012)

6500^ Background: Blinatumomab is a bispecific T-cell engaging (BiTE) antibody that directs cytotoxic T-cells to CD19 expressing target cells. Methods: In adult patients with relapsed/refractory B-precursor ALL, a phase II dose ranging trial is being conducted to evaluate efficacy and safety of blinatumomab. The primary endpoint is the rate of hematological complete remission (CR) or CR with partial hematological recovery (CRh*) within 2 cycles of blinatumomab treatment. Blinatumomab is administered by continuous intravenous infusion for 28-days followed by a 14-day treatment-free interval. Responding patients can receive 3 additional cycles of treatment or proceed to bone marrow transplantation. Three dose levels were explored as shown in the table. Results: In total 36 patients have been enrolled, 25 are currently evaluable. Seventeen out of 25 treated patients (68%) reached a hematological CR/CRh* and a minimal residual disease (MRD) response (MRD level &lt;10 -4 ) within the first 2 cycles. Five out of 17 responders (29%) showed a CRh* due to partial recovery of platelets. For the first 18 patients, response duration is 7.1 months and the median follow-up time for overall survival (OS) is 9.7 months (median not reached). Six cases of relapses have been recorded of which 3 were CD19 + , and 3 CD19 - . As final dose 5 µg/m²/day in week 1 and 15 µg/m²/day for the remaining treatment (cohort 2a and 3) was selected. In these cohorts (n=12), the most common treatment emergent adverse events (TEAEs, all grade 1-2) were pyrexia (67%), headache (33%) and tremor (33%). TEAEs of grade ≥3 (7 in 5 patients, no grade 4), irrespective of relationship, were infections, confusion, epilepsy, hypertension and thrombocytopenia. Conclusions: The final dose was well-tolerated and produced an exceptionally high complete remission rate. A global phase 2 study to confirm these data is underway. [Table: see text]