tbuckley/cabot-search huggingface dataset:
Novel oral combination chemotherapy in the treatment of intermediate-grade and high-grade AIDS-related non-Hodgkin's lymphoma.
Authors: S C Remick, J J McSharry, B C Wolf, C G Blanchard, A Y Eastman, H Wagner, E Portuese, T Wighton, D Powell, T Pearce
Journal: Journal of Clinical Oncology (1993)

PURPOSE To determine the toxicity, response, and survival rate of orally administered combination chemotherapy in patients with AIDS-related intermediate- and high-grade non-Hodgkin's lymphoma. Secondary objectives included prospective quality-of-life assessment and quantitation of cell-associated p24 antigen (p24 Ag) by flow cytometry. PATIENTS AND METHODS Eighteen patients with biopsy-proven lymphoma were treated with oral chemotherapy consisting of lomustine (CCNU) 100 mg/m2 on day 1, etoposide 200 mg/m2 on days 1 through 3; cyclophosphamide 100 mg/m2 on days 22 through 31, and procarbazine 100 mg/m2 on days 22 through 31 at 6-week intervals. A variety of clinical assessments were performed: prospective quality-of-life assessment using the Functional Living Index-Cancer (FLIC) and Brief Symptom Inventory (BSI) instruments; indirect immunofluorescence with flow cytometry to measure cell-associated p24 antigen; and price of the oral regimen compared with two other intravenous combination chemotherapy regimens. RESULTS The overall objective response rate using Eastern Cooperative Oncology Group (ECOG) criteria was 61% (95% confidence interval, 39% to 84%), with seven complete remissions (39%) and four partial remissions (22%). The median survival duration was 7 months, with a range of 11 days to 36 months. The treatment-related mortality rate was 11%. One patient developed CNS progression. Myelosuppression was the most frequent and severe toxicity encountered. Predictor variables of performance status (PS), prior history of thrush, and CD4 lymphocyte count were found to be of prognostic value. In a separate analysis, scores on the three subscales of the BSI were also found to be predictive of complete response. The price of this regimen is several thousand dollars less than that of other intravenous combination chemotherapy regimens. CONCLUSION This regimen is active in patients with AIDS-related non-Hodgkin's lymphoma. Because it is important to design systemic cytotoxic chemotherapy regimens that are cost-effective, considerate of quality-of-life issues, and efficacious in this patient population, this approach should be compared with standard intravenous combination chemotherapy regimens in randomized controlled clinical trials.
Tolerability of long-term use of trabectedin (Tr) in combination with pegylated liposomal doxorubicin (PLD) in patients (pts) with relapsed ovarian cancer (ROC).
Authors: I. Romero, N. Colombo, S. B. Kaye, J. Arranz, A. Roszak, D. M. Provencher, P. Santabarbara, E. Bayever, E. Almorin, F. Muggia
Journal: Journal of Clinical Oncology (2010)

5121
Male breast cancer in veteran population: Retrospective analysis of VACCR database.
Authors: S. Subbiah, T. Tashi, W. Gonsalves, M. Kalaiah, N. Didwaniya, R. Thota, S. Kanuri, P. Townley, I. Aldoss, P. T. Silberstein
Journal: Journal of Clinical Oncology (2010)

1031 Background: Male breast cancer (MBC) accounts for less than 1% of all breast cancers. Its rarity has to lead to extrapolation of its clinical, pathological characteristics and treatment from female breast cancer studies. Methods: A total of 939 patients diagnosed with male breast cancer from 1995 to 2009 were identified from the VA Central Cancer Registry (VACCR) database. Age, race, histology, lymph node status, hormone status, and type of treatment received data were collected. Results: Out of 939 patients, 697 (74.2%) were white, 227 (24.2%) were black, and 14 patients were listed as unknown. Median age was 68 years (range 23-93 years). Pathological T-stages were as follows:T1=237 (25.2%),T2=304 (32.4%),T3=25 (2.7%),T4=62 (6.6%), and unknown 259 (27.6%). Of the total, 681 (72.5%) were ductal carcinomas whereas 549 (58.5%) were ER/PR positive. 315 (33.5%) were lymph node positive, 325 (34.6%) were lymph node negative, and 299 (31.8%) were unknown. Histologically grade 2 (37.5%) was most commonly reported followed by grade 3 (23.4%) and in 25.7% grade was unknown. 292 (31.1%) patients received only surgery while 489 (52.1%) received surgery with adjuvant chemotherapy, radiation or a combination of both, 73 (7.8%) patients received either chemotherapy, radiation or hormonal therapy alone, 85 (9%) did not receive any therapy. After surgical resection, 287 (30.6%) received adjuvant hormone therapy.Overall median survival was 6.92 years. 5-year survival for each stage were as: stage 1= 80.6%; stage 2=59.8%; stage 3= 47.6%; stage 4= 25%. Median survival for lymph node positive patients is 6.4 years and in lymph node negative 9.4 years (p=0.003, HR 0.69). Conclusions: MBC survival rates are lower than female breast cancer. Median age of diagnosis of MBC is higher than their female counterparts and more than half of them are hormone receptor positive. Lymph node status plays a significant role in survival of MBC patients. Due to rarity of the disease further multi-institute studies are required for more in-depth understanding and analysis of this uncommon disease. No significant financial relationships to disclose.
Weekly doxorubicin in endocrine-refractory carcinoma of the prostate.
Authors: F M Torti, D Aston, B L Lum, M Kohler, R Williams, J T Spaulding, L Shortliffe, F S Freiha
Journal: Journal of Clinical Oncology (1983)

Twenty-five patients with endocrine-refractory prostatic carcinoma were treated with doxorubicin, 20 mg/m2 given weekly. All patients had prior hormonal therapy (68% had two or more prior hormonal maneuvers), and 21 (84%) had prior therapeutic or palliative irradiation. Median Karnofsky performance status at the time of entry was 70. Hemoglobin was less than 12.0 g/dL in 15 patients. Bidimensional tumors were present in 12 patients in 19 disease sites; four of the 12 patients (33%) responded in eight of the 19 sites (42%); and three of eight patients had a 75% decrease in prostatic nodule size. Ten of 20 evaluable patients had an improvement of 20% or greater in Karnofsky performance status and 67% (14 of 21) had marked improvement in pain. A greater than 50% reduction or normalization of acid phosphatase occurred in 19% and of alkaline phosphatase in 53%. The overall response rate by National Prostatic Cancer Project criteria was 84%. Gastrointestinal toxicity and alopecia were minimal and myelosuppression was not life threatening in any patient.
Antitumor effects of sorafenib and sunitinib in patients (pts) with metastatic renal cell carcinoma (mRCC) who had prior therapy with anti-angiogenic agents
Authors: I. Tamaskar, P. Shaheen, L. Wood, S. Hodnick, C. Nemec, J. Garcia, R. Dreicer, B. Rini, R. Bukowski
Journal: Journal of Clinical Oncology (2006)

4597 Background: Sorafenib and sunitinib are multi-targeted kinase inhibitors (TKI’s) with clinical activity in mRCC. Their effect in mRCC pts refractory to prior anti-angiogenic agents is unclear. We investigated the anti-tumor effect of sorafenib and sunitinib in patients with mRCC who failed prior treatment with anti-angiogenic agents. Methods: Pts with mRCC receiving sorafenib and sunitinib on compassionate use trials were identified. Those pts who had received prior treatment with anti-angiogenic agents defined as thalidomide, lenalidomide, M200 (anti-α5β1 integrin monoclonal antibody), bevacizumab, AG013736, sunitinib or sorafenib were selected and their treatment response to current sorafenib or sunitinib evaluated. Results: Seventy-two pts (39 receiving sorafenib and 33 receiving sunitinib) were identified. Of these 72 pts, 23 pts (32%) had received prior anti-angiogenic therapy as defined above. Demographics included: 19 male and 4 female, median age 61 years (range 44 to 77). Thirteen pts (57%) are currently evaluable; the remainder are too early for assessment. Twelve pts (92%) demonstrated tumor reduction including 4 pts with objective partial response (PR); 8 pts had stable disease with tumor shrinkage ranging from 4 to 27% and 1 pt had disease progression. Of the 4 PR pts, prior therapy included M200 (1 pt), lenalidomide (2 pts) and sorafenib (1 pt). Of the 13 evaluable pts 4 had failed a prior TKI and received a subsequent TKI and all had evidence of tumor shrinkage to subsequent therapy (sunitinib followed by sorafenib, 1pt - 16% shrinkage, sorafenib followed by sunitinib 2 pts - 33.4% and 24% and AG013736 followed by sunitinib 1 pt - 12% ). Conclusion: Sorafenib and sunitinib have anti-tumor activity in mRCC pts who have received prior anti-angiogenic agents. [Table: see text]
Pegfilgrastim induces elevation of serum CA 15–3 in breast carcinoma patients after receiving dose-dense adjuvant chemotherapy
Authors: C. Saura, E. Vilar, J. Cortes, M. Bellet, A. Ocaña, P. Gomez, J. Baselga
Journal: Journal of Clinical Oncology (2006)

8595 Background: CA 15–3, an epytope related with MUC-1 gene products, is a well known tumour marker to predict early recurrent disease breast cancer. MUC-1 expression can be detected in neutrophil membrane and cytoplasm. It is known that patients with breast cancer who receive adjuvant chemotherapy with G-CSF support may show CA 15–3 false positive elevations Methods: We identified by medical records 76 patients who received adjuvant sequential chemotherapy for breast cancer consisted in Doxorubicin/Ciclophosphamide for 4 cycles followed by Paclitaxel for 4 cycles every-2 (with haematopoietic support with Pegfilgrastim (Cohort A, n=29) or Filgrastim (Cohort B, n=10)) and every-3-weeks without haematopoietic support (cohort C, n=37) between October 2003 and November 2005. Mean values of CA 15–3 recorded at the first follow up (FU) visit after treatment and number of patients with levels above the cut-off value of 40 U/mL were compared between the three patients cohorts. Correlation between CA 15–3 with alkaline phosphatase (AP) levels measured at first FU and with absolute neutrophil count (ANC) mean values measured on day 14 of every cycle were performed for each cohort Results: Patients characteristics between cohorts were well balanced except for age. A statistically significantly difference in median CA 15–3 post-treatment values were observed between Cohort A and C (34.01 versus 22.3, p=0.001), but no between Cohort A and B (34.01 versus 30.53). Eight patients in Cohort A, 2 in B and 1 in C had CA 15–3 levels above 40 UI/mL (27.6% versus 20% versus 2.7%, p=0.009). CA 15–3 decreased to normal values at subsequent visits. CA 15–3, mean ANC (r= 0.272, p= 0.020), and AP (r= 0.361, p= 0.002) were found associated each other when the whole database was analyzed Conclusions: These data provide evidence that Pegfilgrastim induces elevation of CA 15–3 level in comparison with patients treated without G-CSF support. This elevation may be related to the increased neutrophil counts. Physicians should be aware of this fact during the follow up to avoid unnecessary diagnostic workup. [Table: see text]
Predictors for emergency room visits (ERV) and inpatient hospital stay (IH) utilization in elderly veterans with advanced non-small cell lung cancer (NSCLC)
Authors: L. M. Thomas, S. Lappin, M. Gautam, N. Newman, C. Shah, A. Gajra
Journal: Journal of Clinical Oncology (2008)

20572 Background: Diagnosis of advanced NSCLC is associated with significant morbidity in the elderly. Complications of the cancer and/ or its therapy can lead to frequent ERV and IH. High rates of ERV and IH can negatively impact medical center resources. In addition to comorbidities, number of medications especially the Beers criteria medications may predict those at highest risk for ERV and IH. Methods: We carried out a retrospective study at Syracuse VA utilizing logistic regression models to determine statistically significant variables associated with ERV and IH. After IRB approval, patients (> 65 y) with AJCC stage 3/4 NSCLC were identified from 2000 to 2006. Data gathered included: demographics, stage, performance status (PS), use of chemotherapy (CT)/radiation (RT), chronic kidney disease stage, comorbidities using Charlson’s weighted index (CCI) and total comorbidities (TCM), total number of prescription medications (MEDS), medications based on Beer’s criteria. Results: We identified 151 patients with median age of 75 yrs. All patients were male with 65% stage 4 NSCLC, 33 % had good PS (0–1), 24% were on ≥ 1 Beers medication and 33% were on > 8 MEDS. The median CCI score was 2 and median TCM was 5. In univariate analysis, only use of CT and RT therapy was associated with increased ERV and IH (all p values <.02). Paradoxically, stage 3 and good PS also demonstrated strong correlation with ERV and IH (P ≤02). CCI, TCM, MEDS, age or Beers meds did not correlate with ERV or IH. ERV and IH were strongly correlated (r = 0.75, p<.001). When only patients treated with systemic CT were considered, TCM score demonstrated a correlation trend for ERV (r=.23, p=.08) and IH (r=.26, p=.04). MEDS also had a trend for higher ERV (r=.25, p=.06) and for IH (r=0.32, p=.01). Conclusions: In elderly patients with advanced NSCLC, CT and RT use are associated with morbidity leading to ERV and IH. The high ERV and IH rates for good PS and stage 3 likely reflect early diversion to palliative care in poor PS and stage 4 patients. MEDS and TCM reflect a trend towards a higher morbidity in patients treated with CT. If confirmed in larger prospective series, these simple parameters may serve as surrogates in assessing morbidity in the elderly diagnosed with advanced NSCLC. No significant financial relationships to disclose.
My Body, Your Crime
Authors: Muninder K. Dhaliwal
Journal: JAMA (2016)

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Phosphorylated Rho-kinase (ROCK) as a novel therapeutic target in treatment of breast cancer
Authors: S. Shiotani, N. Sadanaga, K. Sugimachi, S. Okada, E. Tokunaga, E. Oki, H. Shimokawa, Y. Maehara
Journal: Journal of Clinical Oncology (2008)

3508 Background: Rho-kinase (ROCK) has been identified as one of the effectors of the small GTP-binding protein Rho. ROCK is activated through phosphorylation (p-ROCK) by activated Rho. Accumulating evidence both in vitro and in vivo has demonstrated that Rho/ROCK pathway plays an important role in invasion and migration of cancer cells. However, it remains to be examined whether ROCK activation is linked to the clinicopathological factors and prognosis of patients with breast cancer. Methods: Primary breast cancer tissues were obtained from 221 patients with breast cancer. The distribution and location of ROCK and p-ROCK protein were evaluated with immunohistochemical staining in paraffin sections. The extent of the immunoreactivity was analyzed in terms of the clinicopathological factors and survival of the patients in the 3-years follow-up period after the operation. Results: The enhanced immunoreactivity of p-ROCK (>20% positive area in total high-power field) was frequently observed in patients with invasive ductal carcinoma (47.1%, n=104), especially in the invasive area of cancer tissue. By contrast, there was no increase in the immunoreactivity in normal breast tissue, in patients with benign fibroadenoma or those with ductal carcinoma in situ. The extent of p-ROCK immunoreactivity was significantly associated with lymph node metastasis (P<0.0001) and lymph vessel invasion (P<0.05). However, no correlation was found with other factors, such as hormone receptor or HER2 protein expressions. The prognosis of patients with enhanced p-ROCK immunoreactivity was significantly poor as compared with those without it (P=0.05). Conclusions: These results indicate that ROCK activation is substantially associated with lymph node metastasis, lymph vessel invasion and prognosis of patients with breast cancer, suggesting a potential usefulness of the combination therapy with chemotherapy and a ROCK inhibitor for the treatment of breast cancer. No significant financial relationships to disclose.
Prediction of the benefit of trastuzumab (T)-based therapy by the change of gene expression of peripheral blood mononuclear cells (PBMC)
Authors: C. Shimizu, K. Tamura, F. Koizumi, O. Komori, M. Pritchard, M. H. Mollah, S. Eguchi, Y. Fujiwara
Journal: Journal of Clinical Oncology (2009)

e14578 Background: Identification of molecular predictors of response is important in the aspect of personalization of treatment, especially in the era of molecular targeted drugs. Antibody-dependent cell-mediated cytotoxicity (ADCC) is suggested as one of the main mechanism of action of T. Moreover, PBMC specimens can securely be obtained with minimal invasion. We therefore hypothesized that gene expression changes induced by T of PBMC may be useful for prediction of response of T. Methods: 36 HER2-positive metastatic breast cancer (BC) patients were enrolled in this prospective biomarker study. The patients were treated with single-agent T (q1w) for chemotherapy-naïve, hormone refractory metastatic disease. The clinical response was measured after 8 cycles of single-agent T. PBMC were collected prior to and 1-week after the first administration of T. Gene expressions of PBMC were measured using Affimetrix GeneChip Human Genome U133 Plus 2.0 array. Change of gene expressions before and after T was correlated with clinical response using Wilcoxon rank sum test. A multi-gene predictor of response to T was generated using the highly ranked genes. The performance of the predictor was then assessed in patients prospectively treated with neoadjuvant chemotherapy (NAC): HER2- positive BC patients recieved NAC containing T. PBMC were collected prior to NAC and 1-week after the first administration of T. Results: 34 patients were evaluable for clinical outcome. 15 and 19 patients were classified as responders and non- responders, respectively. The top 4 genes differentially regulated by T between responders and non-responders were selected for development of a predictor by leave-one-out cross validation. The 4-gene predictor correctly predicted the pathological complete response (pCR) in 5 out of 5 patients who achieved pCR and residual disease (RD) in 10 out of 12 patients with RD (error rate 12 %) in HER2-positive breast BC patients treated with NAC containing T. However, it was not associated with pathological response in 19 HER2- negative patients treated with NAC without T (error rate 39 %). Conclusions: Change in PBMC gene expression after single dosage of T may be useful as a predictor of response to T-based therapy. No significant financial relationships to disclose.
Prognostic value of DNA flow cytometry in the locally recurrent, conservatively treated breast cancer patient.
Authors: B G Haffty, M Toth, S Flynn, D Fischer, D Carter
Journal: Journal of Clinical Oncology (1992)

PURPOSE This study attempted to determine the prognostic value of DNA flow cytometry in the treatment of patients with locally recurrent, conservatively treated breast cancer. METHODS AND MATERIALS Of 433 patients with clinical stage I and II breast cancer treated with conservative surgery and radiotherapy at Yale-New Haven Hospital before January 1985, 50 patients experienced an ipsilateral breast relapse as a first site of treatment failure. Using standard flow-cytometric techniques, DNA ploidy, DNA index, and S-phase fraction (SPF) were measured for 38 of the 50 (76%) paraffin-embedded specimens available for analysis. RESULTS At a median postrecurrence follow-up of 5.8 years, the 5-year and disease-free survival rates following ipsilateral breast treatment failure were 48% and 54%, respectively. Sixty-three percent of the recurrent tumors were DNA diploid and 37% were aneuploid. Both DNA ploidy and SPF were statistically significant prognostic indicators for 5-year survival and disease-free survival after local recurrence. The 5-year survival rate of the DNA diploid population was 64%, compared with 15% in the aneuploid population (P &lt; .02). Patients with low SPF (&lt; 12%) experienced an 83% 5-year survival rate, compared with a 24% 5-year survival rate in patients with high SPF (&gt; or = 12%) (P &lt; .03). Ploidy and SPF were combined to define the categories of favorable (diploid, low SPF) and unfavorable (diploid, high SPF or any aneuploid subgroups). Patients in the favorable category experienced an 89% 5-year postrecurrence survival rate and a 100% disease-free survival rate, whereas patients in the unfavorable category had a 24% 5-year survival rate and a 32% disease-free survival rate (P &lt; .01). The flow cytometry as a factor correlated with other clinical parameters previously shown to be of prognostic significance in this patient population. In a multivariate analysis, flow cytometry was a statistically significant and independent prognostic factor for disease-free survival following local recurrence. CONCLUSIONS DNA ploidy and SPF as measured by currently available flow-cytometric techniques show promise as a tool in determining prognosis for the patient with locally recurrent breast cancer. Implications of these findings with respect to issues of adjuvant systemic therapy at the time of local recurrence are discussed.