tbuckley/cabot-search huggingface dataset:
Determination factors of patients' decision between surgery and chemoradiotherapy for stage I esophageal carcinoma: From the results of JCOG0502—A comparative study of the two modalities.
Authors: Ken Kato, Hiroyasu Igaki, Yoshinori Ito, Isao Nozaki, Hiroyuki Daiko, Masahiko Yano, Harushi Udagawa, Satoru Nakagawa, Masakazu Takagi, Hiroshi Okabe, Tetsuya Abe, Tatsuya Okuno, Jun Hihara, Yasushi Toh, Yasunori Akutsu, Yuichi Shibuya, Junki Mizusawa, Kenichi Nakamura, Haruhiko Fukuda, Yuko Kitagawa
Journal: Journal of Clinical Oncology (2015)

114 Background: Surgery is the standard of care for stage I esophageal squamous cell carcinoma. However, definitive chemoradiothearpy (CRT) is optional treatment which can preserve organ function with cure. The aim of this study was to investigate what factors have influence patients(pts)’ decision on the treatment, surgery or CRT. Methods: JCOG0502 is a randomized controlled trial comparing surgery to CRT. Sufficient information about both treatments was provided for pts before enrollment. Pts who declined to participate in randomized part can choose a preferred treatment and join a non-randomized part of JCOG0502. Between Dec 2006 and Feb 2013, 379 pts were enrolled to JCOG0502 from 37 institutions of Japan Clinical Oncology Group. Among those, 368 pts who enrolled to non-randomized part were analyzed. Clinical baseline data, social data and doctor’s preference which was not mandatory informed to patients were collected on the case report forms and compared between surgery arm and CRT arm. Preference of doctors for each pt was divided into three categories, A: “surgery is preferred”, B: “either is adequate” and C: “CRT is preferred”. This trial was registered as UMIN000000551. Logistic regression were performed to evaluate the influence of each factors. Results: Of the 368 pts, 209 pts chose surgery with their own intention, while 159 pts chose CRT. There were no differences on baseline clinical characteristics between two groups except median age (Surgery: CRT = 62:65 years). Multivariate logistic regression analyses showed that &gt;=65 years (vs&lt;65) (OR 2.04, p=0.006), male (vs female) (OR 2.10, p=0.043), multi-focal primary (vs single) (OR 2.76, p=0.013), status of patient’s children (vs presence of children) (absence of children: OR 2.27, p=0.034) (unknown: OR 4.422, p=0.13), and B or C category of preference of the doctor (vs A) (B:OR 11.67, p&lt;0.001)(C:HR 29.64, p&lt;0.001) were associated with selection of CRT. Conclusions: Older age, male, multifocal primary, absence of children and doctor’s preference are independent factor to choose CRT. Doctor’s preference to each pt was the strongest factor on decision making of patients.
Phase II trial of oral etoposide plus IV irinotecan for patients with platinum-resistant and taxane-pretreated ovarian cancer (JCOG0503).
Authors: Koji Matsumoto, Noriyuki Katsumata, Taro Shibata, Tadao Takano, Ryuichiro Nishimura, Takahiro Kasamatsu, Toyomi Satoh, Motoaki Saitoh, Sadako Nishimura, Noriomi Matsumura, Hiroaki Kobayashi, Satomi Aihara, Takayoshi Nogawa, Toshiaki Saito, Kimio Ushijima, Haruhiko Fukuda, Ikuo Konishi, Toshiharu Kamura
Journal: Journal of Clinical Oncology (2013)

5537 Background: Developing effective chemotherapy for patients (pts) with platinum (Pt) resistant ovarian cancer is unmet medical needs. Topoisomerase inhibitors, such as oral etoposide and iv irinotecan, have been reported to show some efficacy for Pt - resistant ovarian cancer as monotherapy. Combining these two agents should be an intriguing idea. Following phase 1 and feasibility study reported in ASCO2002 and 2005, this study aimed to assess safety and efficacy of oral etoposide plus iv irinotecan for pts with Pt -resistant and taxane pre-treated ovarian cancer (UMIN-CTR ID: UMIN000001837). Methods: Eligible pts are given etoposide at 50 mg/m 2 p.o. from day 1 to 21, and irinotecan 70 mg/m 2 iv, at day1 and day15, repeated every 28 days, up to 6 cycles. Primary endpoint is response rate (RR), secondary endpoints are adverse events, progression-free survival (PFS), and overall survival (OS). As a SWOG two-stage design, at least 55 pts are required with one-sided alpha of 0.05, beta of 0.2 and expected and threshold value for primary endpoint as 35% and 20%. Sixty pts are to be registered. Results: From April 2009 to January 2012, 61 pts were entered to this study. One patient was ineligible, thus 60 pts were analyzed for the study. RR was 21.7% (1 CR + 12 PR, 89% C.I. 13.5 – 31.9 %, one-sided p=0.42). At the data cut-off at November 2012, median PFS and OS were 4.1 (95% C.I. 3.5 – 5.6) and 12.4 (95% C.I. 10.1 – 14.8) months, respectively. Six months-PFS was 35.0 %. For pts with Pt --free interval (PFI) &gt;= three months (n = 33), RR was 30.3 % (95% C.I. 15.6 -48.7 %), median PFS and OS was 5.8and 16.9 months, respectively. For safety, G3/4 neutropenia, anemia, and thrombocytopenia were 60.0 %, 36.7 % and 11.7%, respectively. G3/4 non-hematological toxicities over 10 % were febrile neutropenia (FN) (18.3%), fatigue (13.3%), nausea (11.7 %) and anorexia (11.7 %). FN was more frequent in elderly pts of 65 years or older (28.6 %). Two treatment-related deaths occurred, both in elderly. Conclusions: As a whole, this regimen did not meet primary endpoint for further phase 3 study. Elderly pts should be treated very cautiously with this regimen. However, promising efficacy could be expected for those with PFI &gt;= 3 months. Clinical trial information: UMIN000001837.
More misleading science from the tobacco industry
Authors: Michael J Thun
Journal: BMJ (2003)

Delaying clean air laws through disinformation 

From BMJ USA 2003;July:352 

The article by Enstrom and Kabat (p 369) is the latest in a long series of publications funded by the tobacco industry that report little or no relationship between environmental tobacco smoke (ETS) and disease.1 The current study has an aura of legitimacy because it is drawn from the American Cancer Society (ACS) Cancer Prevention Study I (CPS-I), a landmark prospective study of the hazards of active smoking,2 and because the analyses are based on nearly 40 years of data. Despite these apparent strengths, the study by Enstrom and Kabat is uninformative and its conclusions are exaggerated.

Indeed, the negative conclusions were entirely predictable from the outset because of the flawed way in which exposure to ETS was classified. CPS-I collected no information on ETS exposure other than the smoking status of the spouse. The study began in 1959, an era in which secondhand smoke was pervasive; virtually everyone was exposed at work, in social settings, or in other activities of daily living. Enstrom and Kabat therefore could not identify a comparison group of “unexposed” persons. Their analyses essentially compare nonsmokers married to a smoking spouse to nonsmokers with other sources of ETS exposure. This potential for misclassification was further exacerbated in the final 26 years …
Incidence of central port failure among patients receiving bevacizumab.
Authors: A. Muslimani, R. Reid, H. Daw, S. M. Wills, S. K. Wang, I. A. Jaiyesimi, D. Decker
Journal: Journal of Clinical Oncology (2010)

e19579 Background: Central venous port (CVP) failure is a common problem in cancer patients (pts) during chemotherapy. Risk factors include increasing age, male gender, and hematogenous malignancy. The incidence of CVP failure in adult cancer pts previously reported in the literature ranges from 3.4–10%, with infection as the most common cause. Pts receiving Bevacizumab (bev) showed an increase in wound dehiscence, as well as increase thromboembolic event. We conducted a study to determine the frequency of port failure among pts receiving bev. Methods: A multi-center chart review of cancer pts receiving ≥ 2 doses of bev from Cleveland Clinic Cancer Center (Moll Pavilion) and Beaumont Hospitals was conducted. All pts had a CVP placed between July 2006 and August 2009. Pts who had wound adhesions, CVP failure due to infection, without proper monthly heparinization were excluded. The incidence of CVP failure was calculated. CVP failure was defined as difficulty to inject and blood draw requiring port removal. Results: We identified 164 pts (61 males; 103 females; age range 36-88). Twenty eight pts (17 %) experienced CVP failure (9 males, age 42-79). There were 18 breast, 5 colorectal and 5 non-squamous cell lung cancer pts. Median follow up was 142 days (range 30-258). The CVP was placed 59% in the left side, and 41% in the right side of the chest. Using Venography to assess the case of malfunction; thrombus or fibrin sheath was the most common cause of failure (16 Pts) 57%, other causes (disconnection, cath rupture or fracture) in (7 pts) 25%, and the venograph was normal in (5 pts) 18%. The proportion of CVP failure in pts receiving bev in this study is significantly higher than previously reported. Since we excluded infection as a cause of the CVP failure, it is likely that the observed CVP failure was underestimated. Conclusions: Bev is associated with a higher rate (17%) of CVP failure compared with previous reports even after excluding infection as a cause. The thrombus as the main cause may be secondary to bev increasing thromboembolic event. Since the number of pts is small, a prospective cohort study is needed to verify our results. No significant financial relationships to disclose.
Ribosomal DNA (rDNA) spacer polymorphism in mole rats.
Authors: H Suzuki, K Moriwaki, E Nevo
Journal: Molecular Biology and Evolution (1987)

Genetic differentiation of ribosomal DNA (rDNA) nontranscribed-spacer (NTS) polymorphism was analyzed in 50 individuals from 13 populations among the four chromosomal species (2n = 52, 2n = 54, 2n = 58, and 2n = 60) of subterranean mole rats of the Spalax ehrenbergi complex in Israel. Southern blot analysis with a mouse rDNA probe and two restriction enzymes, EcoRI and BamHI, revealed various sizes of major restriction fragments. The assumption that this variation is due to length polymorphism of NTS DNA was supported by the construction of restriction-site maps. On the basis of the EcoRI and BamHi fragment lengths, we could characterize the major types of NTS rDNA repeating units in each individual. Each member of the central population in the four chromosomal groups of mole rats has a characteristic combination of the NTS types, suggesting that the karyotype groups were genetically diverged. Some near-hybrid-zone populations reflect similarities with the rDNA spectra of a neighbor chromosomal group. This might have resulted from gene flow across the hybrid zones.
Results of a phase II clinical trial of 2 doses and schedules of CP-675,206, an anti-CTLA4 monoclonal antibody, in patients (pts) with advanced melanoma
Authors: A. Ribas, S. Antonia, J. Sosman, J. M. Kirkwood, B. Redman, T. F. Gajewski, D. Pavlov, C. Bulanhagui, J. Gomez- Navarro, L. H. Camacho
Journal: Journal of Clinical Oncology (2007)

3000 Background: CP-675,206 has antitumor activity in pts with metastatic melanoma. A 2-stage, 2-arm phase II trial was conducted to choose the optimal dosing regimen for pivotal clinical trial testing. Methods: Eligible pts had measurable melanoma (stage IIIc or IV) progressing on or after prior therapy with ECOG PS = 1. In stage 1, 18 pts per arm were randomized to either 10 mg/kg monthly (10 Q1M) or 15 mg/kg every 3 months (15 Q3M). If 3 or more pts in either arm had CR or PR, then 25 more pts were entered to that arm. Primary endpoint was objective tumor response, and secondary endpoints were safety and survival. Results: 89 pts received at least 1 dose (44 at 10 Q1M, 45 at 15 Q3M), with both study arms moving to stage 2. 96% of pts had stage IV disease, and 57% had elevated LDH. There were no significant differences in age, sex, stage, or baseline LDH levels between study groups. A median of 3 doses (range, 1 to 26) at 10 Q1M and 1 dose (range, 1 to 9) at 15 Q3M were administered with 100% compliance. Dose delays occurred in 30% of pts treated at 10 Q1M and 16% at 15 Q3M. 2 pts at 10 Q1M and 5 pts at 15 Q3M continued on study beyond 12 months (mo). To date, 6 pts at 10 Q1M have been discontinued due to toxicity (3 diarrhea/colitis [1 requiring colectomy], Grave’s ophthalmopathy, pancreatitis, hypersensitivity reaction) and 2 pts at 15 Q3M (colitis and pancreatitis, diarrhea) (P = 0.14). There were no toxic deaths. 15 Q3M was associated with lower incidence of grade 3 or 4 AEs (31% vs 41% at 10 Q1M; P = 0.42). Responses by investigator assessment were 1 CR and 3 PRs at 10 Q1M, and 1 CR and 2 PRs at 15 mg/kg Q3M, including responses in skin, LN, bone, liver, lung, and adrenal glands. To date, only 1 pt with PR at 10 Q1M has relapsed, and the remaining responses are ongoing (18+ to 28+ mo). Median survival is 10.3 mo at 10 Q1M and 11.0 mo at 15 Q3M (P = NS). Conclusions: The 15 mg/kg Q3M regimen was chosen for further clinical testing based on comparable antitumor efficacy and a trend to improved feasibility and safety compared with 10 mg/kg Q1M. CP-675,206 at this dose and schedule is being examined in pivotal phase II and III clinical trials for pts with melanoma, and in early phase II trials in pts with CRC and NSCLC. No significant financial relationships to disclose.
Deep electro-hyperthermia (EHY) with or without thermo-active agents in patients with advanced hepatic cell carcinoma: Phase II study
Authors: V. D. Ferrari, S. De Ponti, F. Valcamonico, V. Amoroso, S. Grisanti, G. Rangoni, P. Marpicati, L. Vassalli, E. Simoncini, G. Marini
Journal: Journal of Clinical Oncology (2007)

15168 Background: Advanced HCC has no standard chemotherapy , all pts would be valuabled in clinical trials. We evaluated effectiveness and toxicity of capacitatively coupled low-frequency 13.56 MHz deep hyperthermia (Oncotherm-EHY 2000) treatment on chemo- refractory malignant primary liver cancer which underwent all other possible treatment. Methods: From February 2005 to July 2006, we enrolled 22 pts with advanced HCC. ECOG PS was 1 or O. Viral hepatic infection status was 7 HBV+, 8 HCV+, 1 HCV/HBV+. Median age was 67,5 y (range 63 -78), male/female 20/2 . 15 pts were uneligible for liver surgery, 3 pts received TACE, 1 PEI, 1 a lot of therapy. 7 pts were pre-treated with surgery, 2 also received TACE, 1 PEI and 1 a lot of therapy. 75% of pts were in stage C of BCLC classification. 2 pts had also distant metastases, 70% of pts had portal vein thromboses. 8 pts underwent only to EHY without CT. Schedule : EHY was achieved by arrangements of capacitative electrodes with a radiofrequency field of 13.56 Mhz (RF-DHT) at 80- 130 W equivalent to 41 °- 47° C for 60 minutes, 2 times/w for 5 weeks in combination with thermo-active agents . EHY was applied over 2 time a week over 1 hour as mono - combined therapy . Concomitant chemotherapy was oxaliplatin 50 mgr at fixed dose on D 1and D 15 . One cycle is 10 treatments of EHY ; 4 pts underwent 2 cycles and 2 pts to 3 cycles and 1 pt to 4 cycles . Median number of cycles was 1,5 (range 1–4), total EHY applications were 365. Results: EHY plus thermo-active drug is beneficial on clinical conditions off treated pts with an excellent compliance on out- patients. We observed 1 CR ( pt has only one bone metastases after 6 months without liver relapse), no PR, 25% of SD. Median survival time was 20’5 weeks (5 - 81+) We noted that 11 pts (50%) presented evidence of increasing well-being. Toxicity : 4 pts had skin reaction after application of EHY. In 3 pts we observed cutaneous hyperemia on the area of treatment and mild burn on the skin ; all symptoms disappeared after local steroid therapy , treatment was interrupted until resolution . Conclusions: Low toxicity and clinical benefit will be confirmed in further clinical studies. Capacitively coupled low-frequency 13.56 deep-hyperthermia is feasible for chemo-refractory HCC. No significant financial relationships to disclose.
Outcome of patients with glioblastoma multiformae (GBM), treated with pre-radiation chemotherapy and concomitant chemoradiation followed by post-radiation treatment using continuous low dose temozolomide schedule
Authors: S. Kurian, E. B. Crowell
Journal: Journal of Clinical Oncology (2005)

1577 Rationale: To study the effect of low dose daily temozolomide in non-irradiated patients with resected GBM, in view of the possibly improved drug delivery prior to radiation induced changes in the tumor bed. Continuous administration schedule was based on the fact that, continuous exposure to temozolomide has shown to deplete the enzyme responsible for acquisition of drug resistance. This is a single institution phase II study with planned enrollment of 10 patients. Method: Patients who underwent near total excision of their GBM were started on temozolomide 75 mg/m2/day for six weeks given on an eight-week cycle. Patients were given one cycle prior to radiation therapy, followed by concomitant chemo-radiation and the same schedule of chemotherapy continued post- radiation, until tumor progression. Patients underwent weekly blood count and monthly MRI throughout the treatment. Results: The first 2 patients enrolled showed progression during the pre-radiation phase, and the protocol was amended to start radiation concommitantly with the first cycle of chemotherapy. There was high incidence of prolonged grade 4 neutropenia and bilateral lung infiltrates, including one death from progressive sepsis. Conclusion: Even though phase II and III studies have shown survival benefit for using temozolomide during radiation therapy, caution should be exercised in the elderly and immunosuppressed patients. Appropriate prophylactic antibiotic therapy is essential in these patients. Future studies should include correlation with biological markers, not only to predict response, but also to attempt to identify patients at high risk for toxicity. The continuous administration schedule provides higher cumulative drug dose, likely resulting in excess toxicity than the bolus regimen and the latter schedule may be preferrable in the post radiation phase. In summary, our study supports that the continuous schedule temozolomide has activity with brain radiation, but this schedule was ineffective as a pre-radiation therapy, and also appears to be associated with excessive toxicity with prolonged use. No significant financial relationships to disclose.
Increased Troponin-T level is associated with anthracycline-induced diastolic dysfunction of the left ventricle
Authors: S. Kilickap, I. Barista, E. Akgul, K. Aytemir, S. Aksoyek, I. Celik, S. S. Kes, G. Tekuzman
Journal: Journal of Clinical Oncology (2004)

9722 Background: The serum troponin-T (cTnT) level increases with myocardial damage. We sought to assess whether cTnT level could be a useful marker for the early detection of anthracycline cardiotoxicity. Methods: 41 Patients who had been planned to receive anthracycline containing combination chemotherapy were included into the study. Serum cTnT levels were measured before (baseline) and after first cycle of chemotherapy, and repeated after the last cycle of chemotherapy. In all patients, the left ventricular ejection fraction (LVEF), fractional shortening (FS), early peak flow/atrial flow (E/A) velocity ratio, and the isovolemic relaxation time (IRT) were measured echocardiographically, both before and after the study. Results: LVEF and FS did not change in any patients. In 21 patients (49%), the E/A ratio decreased after therapy. The decrease in E/A ratio was more prominent in patients who were older than mean age of our study group which was 44 years (p<0.05). The post-therapy IRT was prolonged (94.0±2.0 vs 85.6±10.5 msec). cTnT levels after completion of therapy were elevated in 14 (34%) patients, but it exceeded the upper limit of normal range (>0.01 ng/mL) only in a single case. cTnT levels after completion of therapy were significantly higher, compared to those baseline and after the first cycles of therapy (p<0.05). In the younger age group (≤44 years), there was a 2-fold decrease in the E/A ratio in patients whose cTnT levels increased during the therapy, compared to those whose cTnT levels did not change (21% vs 43%, p<0.05) (Table 1). Conclusions: Increased serum cTnT levels can be detected in the early stages of anthracycline therapy and it is associated with diastolic dysfunction of the left ventricle. Therefore, serum cTnT level could be a useful marker for the early detection of anthracycline-induced cardiomyopathy. No significant financial relationships to disclose.
More thoughts prompted by the Bristol case
Authors: C Thomson, R. Hopkins
Journal: BMJ (1999)

Editor—I can readily identify myself as one of the two consultants principally concerned with the case of whistleblowing or professional assassination reported anonymously as a personal view.1 Many of the problems we had with reporting poor performance should be resolved if the new formal procedures and assessments of the General Medical Council (GMC) work. However, the central issue of a practitioner’s first responsibility being to protect patients from underperforming colleagues by speaking out remains. It will be difficult to reassure doctors about the consequences to themselves of so reporting if, later, accusations of malice or personal motives are cited. The alternative of anonymous reporting is unacceptable since it would then be easier to make malicious accusations and it is normal in law for people making accusations to be available for cross examination by the accused.

A major problem is for doctors to know at what point a level of failure is significant. In my case, questions from general practitioners, requests for second opinions, and complaints from junior doctors who were willing to cite the cases that worried them were sufficient for me to act. The subsequent process of suspension is clearly damaging to a doctor, but the decision must be taken exclusively by the management as part of a risk assessment. The preliminary screening in the GMC’s new procedure should probably be the stage at which a decision can be made on the evidence provided to suspend the practitioner or permit him or her to continue at work while being investigated; the screeners will become familiar with accepted standards in each specialty.

My experience of the management’s independent assessment was wholly unsatisfactory: we were not told who carried it out but simply that “the frequency and degree [of errors that we reported] could be considered acceptable medical practice.” Such assessments probably explain why Tomlin reports that in only two of 28 cases that he surveyed was fault proved against the accused doctors.2 Neither were we told of any advice given to our colleague to modify his practice. This is unsatisfactory, since those making complaints have no feedback and cannot evaluate their own actions. I would recommend that this aspect was addressed in the formal GMC procedure so that there is an evolving and published set of standards.

Sometimes in professional work we have to do what we think is our best and take partially informed criticism on the chin. That is what I have learnt from blowing the whistle.