bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy and tolerability of fentanyl buccal tablet (FBT) in opioid-tolerant cancer patients with neuropathic pain
Authors: Thakur R. , Vaughan J. A. , Messina J. , Xie F. , Taylor D. R.
Published: March 2020

19549

Background: Fentanyl buccal tablet (FBT), a new formulation recently approved by the FDA for opioid-tolerant patients with cancer-related breakthrough pain (BTP), provides rapid-onset analgesia. Neuropathic pain is the primary pain pathophysiology in a significant proportion of patients with chronic cancer pain; therefore, the efficacy and safety of FBT was studied in this subpopulation. Methods: The efficacy and safety of FBT in the treatment of BTP in opioid-tolerant cancer patients with neuropathic pain were evaluated as a sub-analysis of two randomized, double-blind, placebo-controlled studies. Of the 45 patients in the sub-analysis (50% male, 86% white, mean age 56 years), 30 identified an effective FBT dose during open-label titration and were randomly assigned to double-blind crossover dose sequences of 10 tablets (7 FBT, 3 placebo). Pain intensity (PI) and pain relief (PR) were recorded at intervals after dosing. The primary efficacy measures were the sum of pain intensity differences (PIDs) for the first 30 (SPID30) and 60 minutes (SPID60); secondary efficacy measures included PIDs, PR, and total pain relief (TOTPAR). Use of supplemental BTP medication and adverse events (AEs) were recorded. Results: Combined data (all values mean ±SD) favored FBT vs placebo for SPID30 (3.35±3.11 vs 1.88±2.58) and were significant for SPID60 (9.90±7.19 vs 5.51±6.06; 95% CI, 2.99, 5.81). There was a greater reduction in PI following FBT vs placebo at 10 minutes (PID, 0.55±0.89 vs 0.24±0.48), which continued through observation periods of up to 2 hours (3.43±2.44 vs 1.95±1.99). Higher PR scores were noted following FBT vs placebo at 10 minutes (0.43±0.39 vs 0.21±0.28), which continued for up to 2 hours (1.99±0.72 vs 1.36±0.60). TOTPAR was better following FBT vs placebo at 15 (0.88±0.89 vs 0.48±0.73), 30 (2.42±1.85 vs 1.40±1.65), 45 (4.29±2.90 vs 2.61±2.68), and 60 minutes (6.34±4.02 vs 3.94±3.81). Patients were more than twice as likely to require supplemental opioids for BTP episodes following placebo vs FBT. AEs were typical for opioids; e.g., headache (23%), nausea (18%), dizziness (18%), vomiting (14%), and fatigue (11%). Conclusions: FBT was effective and well tolerated in a subgroup of cancer patients with BTP in association with chronic neuropathic pain.

No significant financial relationships to disclose.
Increased incidence of non-melanomatous skin cancer in patients with chronic lymphocytic leukemia, an 11-year case-control study
Authors: Schoen M. W. , Gable P. S. , Reese A. M.
Published: March 2020

19554

Background: Chronic Lymphocytic Leukemia (CLL) is a disease of B lymphocytes that affects immune tolerance and surveillance. Patients with CLL have an increased risk of basal and squamous cell skin carcinomas, which tend to be aggressive. We report the incidence of non-melanomatous (NM) in a >80% Caucasian cohort of patients with CLL and compared them to normal controls who reside in Southern California. Methods: A retrospective review was conducted of all patients in the Naval Medical Center San Diego tumor registry with CLL diagnosed between Jan 1, 1995 and Dec 31, 2005. The electronic records of 74 CLL patients and 100 control patients from the internal medicine clinic were assessed for skin biopsies performed at our institution revealing NM skin malignancies. Results: Within our CLL population, the average age at diagnosis was 72.2 years. 34% (25/74) had NM skin cancer with an incidence of 11,457 NM skin cancers per 100,000 person-years. The average number of malignant lesions was 3.7 per patient with one patient receiving 17 biopsies. 27% (7/25) of CLL patients with NM skin cancer had only squamous cell carcinoma and 23% (6/25) had only basal cell carcinoma. 42% (11/25) of patients had both squamous and basal cell cancers and one had a Merkel cell carcinoma. In the control population, the average age at diagnosis was 76.4 years. 16% (16/100) had NM skin malignancies with an incidence of 5,333 NM skin cancers per 100,000 person-years. The average number of malignant lesions was 3.7 per patient with one patient receiving 28 biopsies. 63% (10/16) had basal cell carcinomas, only 25% (4/16) had squamous cell carcinomas and 13% (2/16) had both types of cancer. Conclusions: Patients with CLL are at increased risk of developing NM skin cancers, especially squamous cell carcinomas. Patients with CLL have a 2.1 times higher risk of developing NM skin cancer than our control population, who had an incredibly high rate of skin cancer compared to prior publications. CLL patients should be closely screened for cutaneous malignancies in order to excise them before they cause further morbidity. Increased surveillance is especially prudent for elderly patients with fair skin types who have been exposed to a large amount of UV-light.

No significant financial relationships to disclose.
Celiac disease and chemotherapy
Authors: Robinson S. I. , Murray J. , McWilliams R. R.
Published: March 2020

19561

Background: Diarrhea is a common side effect of chemotherapy (CT). At times, often unpredictably, patients develop profound diarrhea during CT. Though the clinical diagnosis of celiac disease (CD) is relatively rare, (1/ 2000), the serologic prevalence is much higher (1/ 133), suggesting a large number of undiagnosed cases. Latent CD may be unmasked by stressors, such as CT. We hypothesized that undiagnosed CD may account for some cases of severe diarrhea from CT. Methods: We performed a retrospective chart review at the Mayo Clinic (1980–2006) for patients with diagnoses of cancer and CD that received CT at our center. CD cases were confirmed by biopsy (n= 25) or serologic studies. Data analyzed included severe (grade ≥ 3,) diarrhea while on CT, site of primary cancer, diagnosis of CD prior to or after CT, and specific CT agents received. Results: We identified 27 patients with CD and cancer (12 lymphoma, 6 gastrointestinal, 2 leukemia, 2 breast, 1 brain, bladder, lung, uterine, sarcoma) who received CT at our center. Fifteen were diagnosed with CD prior to receiving CT and 12 after, with the former group presumably on a gluten-free diet. One patient was excluded for lack of clinical data. Five of remaining 14 patients (35%) managed for their CD prior to CT had diarrhea, though 4 of these 5 had only mild diarrhea (gr. 1). One patient suffered gr. 3 diarrhea, though was reported to be poorly compliant with his diet. Three patients received treatment with 5- fluorouracil (5FU), and 2 had gr. 1 diarrhea. Five of the 12 patients (42%) with celiac disease undiagnosed prior to CT were reported to have diarrhea during treatment (3 gr. 4; 2 gr. 1). Of those receiving 5FU, 3 out of 4 had severe (gr. 4) diarrhea. The small numbers of patients precluded meaningful statistical analysis. Conclusion: Patients with known CD compliant with a gluten-free diet tolerated CT well. However, in a subset of undiagnosed patients, severe diarrhea developed during CT, most notably with 5FU-based regimens. We propose that when patients have diarrhea disproportionate to other effects, CD should be considered. Also, in malignancies with a high incidence of CD such as lymphoma and small bowel cancer, underlying CD should be considered before CT is given.

No significant financial relationships to disclose.
Phase II trial of pegylated liposomal doxorubicin-cyclophosphamide combination as first-line chemotherapy in elderly metastatic breast cancer patients
Authors: Dufour P. R. , Rousseau F. , Meyer N. , Delozier T. , Serin D. , Nabet M. , Djafari L. , Kurtz J.
Published: March 2020

19565

Background: Although the majority of metastatic breast cancer (MBC) patients (pts) responds to endocrine therapy, treatment failure is a concern, as well as front-line therapy for pts with ER/PR negative disease.The combination of anthracyclines (A) and cyclophosphamide (C) is active in younger pts, but cardiac toxicity of A in elderly MBC pts has to be considered. Pegylated liposomal doxorubicin (PLD) (Caelyx®) is active in MBC and has much less cardiotoxicity than A, and we present the preliminary data of the PLD/C in elderly MBC pts. Methods: This was a multicentric phase II trial. Inclusion criteria included: pts aged between 65 and 75, histologically proven measurable MBC, ECOG PS 0–1, LVEF = 50%, first-line chemotherapy for MBC. Prior adjuvant chemotherapy was allowed if stopped for = 6 or 12 months without and with anthracyclines, respectively. Endocrine therapy either in the adjuvant or metastatic setting had to be stopped for = 1 month. All pts gave a written informed consent. The treatment schedule was : PLD 40mg/m2 and C 500mg/m2 d1 every 4 weeks. Efficacy as well as response duration and tolerance were the primary and secondary end-points, respectively. Results: 35 patients were enrolled (Median age 71.3, range 65.6–75.9). A total of 166 cycles have been administered. The median number of cycles was 6 (range 1–9). No toxic death was reported, one patient died of diabetes mellitus decompensation. No congestive heart failure or decrease in LVEF was reported, although 1 pt experience grade 3 dyspnea and stopped treatment. Other (gr3–4) NCI-CTC toxicity included: neutropenia in 7 (gr3) and 3 (gr4) pts; gr3 mucositis (4). No febrile neutropenia was reported. Grade 3 hand-foot syndrome occurred in 1 pt, whereas treatment was stopped due to a generalized rash in 1 pt. An objective response (CR + PR) was achieved in 10 (28,6%) pts (1 CR and 8 PR), and a disease control in 24 (68.6%) with a progression free survival of 8.8 months and a median survival of 20.4 months Conclusions: The LPD-C combination is active in elderly MBC pts, with an acceptable toxicity profile.

No significant financial relationships to disclose.
Pegfilgrastim can be effectively administered the same day as chemotherapy to prevent neutropenia-related complications
Authors: Gupta N. K. , Thorpe S. , Vanderhoff P. , Gomez S. , Stiltner M. , Alvares D. , Lee D. , Chandler T. , Connelly S. , Clark A. , Bohnen R.
Published: March 2020

19571

Background: Pegfilgrastim has been proven to reduce neutropenia-related complications of chemotherapy. However, the administration of pegfilgrastim 24 hours after chemotherapy treatment often poses an inconvenience for the patients and care givers. Methods: A retrospective chart review of the patients who received pegfilgrastim the same day as chemotherapy was done at a rural oncology practice, where some patients travel more than 100 miles each way for treatment. Incidence of febrile neutropenia (FN), defined as ANC = 500 and temperature =101° F; hospitalization for FN; dose-delay; dose-reduction (= 15% reduction in the planned dose); ANC recovery (ANC=1,500 on the day of next treatment), Grade III/IV neutropenia one week after chemotherapy and empiric use of prophylactic antibiotics was recorded. Results: Between 11/05 and 11/06, 243 doses of pegfilgrastim were given the same day as chemotherapy to 48 patients. M/F=14/34; Age(median): 61.2 yrs (range: 27–88 yrs).The diagnoses were NSCLC=13 (Stage II, III, IV: 2, 2 and 9, respectively); Breast Ca=11 (stage II, III, IV: 4, 6 and 1, respectively); Diffuse large B-cell lymphoma (DLBCL)= 6 (stage III, IV: 4, 2); Follicular lymphoma=3 (stage IV: 3); SCLC=3 (stage IV: 3); Ovarian Ca=2 (stage III, IV: 1, 1); and others=10. Twenty five different chemotherapy regimens were administered (Q3 wk. regimens: 19, Q2 wk. regimens: 4 and others=2). No patient had FN or hospitalization for FN. ANC recovery was sub- optimal twice (ANC of 880 and 1,010 on the day of next treatment). Dose was delayed only once due to neutropenia (ANC=880), patient with ANC of 1,010 received treatment as scheduled. Three patients needed dose-reduction of more than 15% (all had DLBCL). Grade III/IV neutropenia after one week of treatment (CBC was available after 235 treatments) was observed in 52 (0.2%) patients, 23 patients had had AC and 25 patients had had CHOP. Empiric prophylactic antibiotics were not given to any patient. Conclusions: Pegfilgrastim can be effectively given the same day as chemotherapy to ameliorate neutropenia-related complications. Same-day administration of pegfilgrastim could improve the quality of life of patients and may reduce the health care costs. Large prospective trials should be done to address this issue.

No significant financial relationships to disclose.
Predictors of outcome and treatment decisions of older patients with stage III non-small cell lung cancer
Authors: Luong D. D. , Poon D. , Gao G. , Boulware D. , Simon G. , Extermann M.
Published: March 2020

19574

Background: In treating Stage III non-small cell lung cancer in the elderly, oncologists often empirically adjust treatment without clear guidelines. Identifying patient characteristics that impact prognosis will aid in creating better treatment algorithms in this patient population. Methods: A retrospective analysis was done on older patients (age > 70) treated for Stage III NSCLC (excluding “wet” IIIB) at the H. Lee Moffitt Cancer. Cox multivariate analysis identified variables impacting progression free survival, overall survival, treatment chosen, treatment interruptions, and hospitalizations. Correlation and regression tree analysis (CART) was performed to create potential decision making models. Results: 213 patients were evaluable. Multivariate analysis identified ECOG performance status (hazard ratio = 1.52, p = 0.005) and nodal status (HR = 1.36, p = 0.001) as negatively associated with PFS while BMI (HR = 0.96, p = 0.02) was positively associated. ECOG performance status (HR = 2.26, p < 0.0001), nodal status (HR = 1.18, p = 0.08), and CIRS3 (having a comorbidity classified as severity 3; HR = 1.33, p = 0.02) were negatively associated with OS. BMI (HR = 0.95, p = 0.002) and CIRSmean (mean CIRS-G severity score; HR 0.61, p = 0.01) were positively associated with OS. These variables were also identified as the most significant splitters, along with smoking status and pulmonary function, in CART analyses. Trees using PFS and OS as outcomes were created with receiver operating curves (ROC) ranging from 0.64–0.75. A CART analysis targeting treatment modality chosen had ROCs ranging from 0.49–0.78. Conclusions: Our multivariate analysis found ECOG performance status, nodal status, and severe medical comorbidity as negatively associated with survival. Unexpectedly, BMI (at initial treatment), independent of weight loss, was found to be positively associated. Also, the splitter variables identified by CART analysis were very similar to the general multivariate model, but the weights differed in the various analyses and subgroups of patients. The CART analyses suggest that we can create decision making models with a range of applicability comparable to those commonly considered useful for clinical guidelines, i.e. about 60% of straightforward application.

No significant financial relationships to disclose.
Increased toxicity associated with delayed clearance of methothrexate (MTX) in patients with lymphoma receiving high-dose MTX
Authors: Huen A. , Romaguera J. E. , Fayad L. E. , Teegala S. R. , Ji Y. , Vadhan-Raj S.
Published: March 2020

19578

Background: High response rates have been observed with the rituximab (R), cyclophosphamide, vincristine, doxorubicin, and dexamethasone (R-HyperCVAD) alternating R-MTX and cytarabine(AraC) regimen in patients with mantle cell lymphoma (MCL). Delayed MTX clearance, related to high dose MTX (1gm/m2) used in this regimen, is an important problem since the common practice is to monitor patients in the hospital for leucovorin rescue, hydration and urine alkalinization to avoid potential toxicity. It is unclear, however, if moderate delay in clearance is associated with increased toxicity. Methods: In this retrospective cohort study, we analyzed toxicity data from pts with MCL who received R-MTX (1gm/m2 given intravenously over 24 hours)/Ara-C as part of the R-HyperCVAD regimen. Delayed MTX clearance was defined as serum MTX level ≥ 0.1 μmol/L at 48 hours after end of infusion. Results: 112 patients received a total of 232 cycles of the (R)MTX/Ara-C regimen. The median age was 61 years (range, 40–80) with 37% of patients over 65 years. Of the 228 evaluable cycles, 80 cycles (35 %) had delayed MTX clearance. Median time to clearance of MTX in the delayed clearance group was 72 hours post treatment (range 72–336 hours). Serum MTX levels at 48 hours from MTX completion in the delayed group ranged from 0.1 to 3.55 micromol/L. The cycles with delayed MTX clearance were associated with more toxicity than cycles with non-delayed clearance as shown in the table below. *(out of 143 evaluable cycles) Conclusions: These findings indicate that patients with delayed MTX clearance at 48 hours are at increased risk for myelosuppression and renal toxicity. These findings suggest future evaluation of the role of Carboxypeptidase (CPDG2), a novel enzyme that cleaves MTX into inactive metabolite, for early intervention in patients with an evidence of delayed clearance at 48 hours to reduce hospitalization and prevent subsequent complications.

[Table: see text]

No significant financial relationships to disclose.
Emergence of quinolone-resistant Escherichia coli at a comprehensive cancer center
Authors: Rolston K. V. , Coyle E. , Prince R.
Published: March 2020

19623

Background: Quinolone prophylaxis is recommended in high-risk neutropenic patients. Although effective in reducing the frequency of febrile episodes and documented gram-negative infections, this approach can lead to the emergence of resistant organisms. Surveillance studies looking for changes in resistance patterns at institutions that care for high-risk patients are also recommended. Methods: Our institution has participated in the meropenem yearly susceptibility test information collection (MYSTIC) program since 2000. The susceptibility of E. coli isolates from our cancer patients to quinolones (ciprofloxacin and levofloxacin) and broad-spectrum agents often used in empiric antimicrobial regimens in such patients, was determined. These studies were conducted by JMI Laboratories, Iowa, USA, and combined results as well as results of each participating institution were provided. CLSI designated breakpoints for susceptibility were used. Ribotyping and PFGE studies were performed on recent isolates. Results: Table 1 documents the declining susceptibility of E. coli isolates to the quinolones. In 2006 only 40.7% were quinolone susceptible compared to 84.2% in 2000 (p = 0.0032). All E. coli isolates remain susceptible to the carbapenems (meropenem, imipenem, ertapenem) and 95.5% remain susceptible to cefepime, ceftazidime, piperacillin-tazobactam, and the aminoglycosides. Twenty-one resistant E. coli isolates underwent ribotyping. Fourteen isolates showed identical ribotype and similar PFGE patterns suggesting the presence of an endemic clone. The other 7 isolates showed variability in their molecular patterns. Conclusions: Quinolone resistance among E. coli strains isolated from cancer patients has increased substantially. Fortunately these isolates remain susceptible to most broad-spectrum beta-lactams and aminoglycosides. Effective infection control methods need to be implemented and enforced in order to reduce the spread of these organisms in high risk patients.

No significant financial relationships to disclose.

[Table: see text]
What can we do for gastrointestinal cancer patients with poor performance status (PS)?
Authors: Shitara K. , Munakata M. , Muto O. , Kasai M. , Sakata Y.
Published: March 2020

19629

Background: The prognosis of advanced gastrointestinal cancer patients, especially those with poor PS, is generally dismal. Needless to say, such patients are ineligible for participation in clinical studies. However, there are many patients with poor PS who wish to receive chemotherapy. Methods: From June 2000 to October 2006, a total of 508 patients with advanced cancer, including 304 gastrointestinal cancer patients, were treated by chemotherapy in our hospital. Of these, 110 gastrointestinal cancer patients (gastric=35, colorectal=30, pancreatic=26, biliary tract=11, esophageal=8) had poor PS (ECOG PS 3 = 68 patients, PS 4 = 42 patients). In 103 patients with at least one measurable lesion, a partial response according to RECIST criteria was obtained in 13 patients (12.6%). In 60 patients with ascites (47 patients), pleural effusion (25 patients), or both (12 patients), 11 of the patients (18.3%) achieved decreased fluid accumulation. A decline in tumor markers (>25%) was observed in 28 patients. Improvement in PS was seen in 13 patients (11.8%). As a result, 35 patients (31.8 %, including 9 patients with PS 4) achieved a tumor response, a decrease in accumulated fluid, or a decline in tumor markers, which resulted in a survival benefit compared to the other 75 patients without effect (6.4 months vs. 2.3 months, p<0.001). Alleviation of some symptoms was observed in 28 out of 98 symptomatic patients (30.4%). A better response and/or a decline in tumor markers significantly correlated with alleviation of symptoms (p<0.001). No treatment related death was seen. Conclusions: With regard to response rate, chemotherapy was rarely effective for patients with advanced gastrointestinal cancer with poor PS. However, more than a few patients gained a certain survival benefit and alleviation of symptoms. Thus, chemotherapy may be warranted in cases of patients with advanced gastrointestinal cancer who wish to receive chemotherapy despite the low possibility of response.

No significant financial relationships to disclose.
Invasive healthcare-associated (HA) environmental fungal infections (EFI) in pediatric oncology (ONC) patients (PTS) are an ever-present risk
Authors: Cox J. , Metcalf P. , Seigel J. , Winick N.
Published: March 2020

19631

To reduce the risk of HA EFI, our ICUs, onc inpatient and stem cell transplant (SCT) units are centrally HEPA filtered and portable HEPA filters are used in each onc outpatient clinic room. Anticipating demolition and then construction of a new, adjacent hospital tower, infection control (IC) verified (Feb 2006) that all windows were completely sealed, provided valet parking remote to the construction and N95 respirators to be worn in all areas except the HEPA filtered locations for immunosuppressed pts to reduce exposure to construction dust; a known risk factor for HA EFI. Eleven new cases of possible HA EFI were diagnosed in 2006: 3 part of a Jan-Feb cluster related to a new construction elevator and malfunction of a door to the outside and 8 clustered July-Oct after demolition and construction began in April. This compares with only 4 cases in 2005. The primary diagnoses in 2006 were AML (6), ALL (4), and hemophagocytic lymphohistiocytosis (1) versus AML (2) and SCT (2) in 2005. Pts with AML and SCT received antifungal prophylaxis or were receiving antifungal therapy at the time of EFI diagnosis. Different isolates were identified including Aspergillus (numerous species), Scedosporium, Fusarium, and Rhizopus; sites of infection included paranasal sinuses (5), pulmonary (6), skin (2) and GI tract (1). 3 of 11 pts died; all required long term antifungal therapy, and most required altered chemotherapy. 4 of 8 pts in the Jul-Oct cluster had been in rooms later found to have faulty window caulking caused by severe weather conditions in Mar 2006. Our data suggest that despite implementation of measures to prevent HA EFI, new sources of outside air and construction dust likely led to an increase in HA EFI. The absence of HA EFI in SCT pts in 2006 may be attributed to the positive pressurization of the SCT unit, location of the unit facing away from the construction site and the antifungal prophylaxis used. The variety of fungi also support outside air as a source. After the faulty caulking was identified and repaired, no further HA EFI occurred; a case-control study is underway to identify important risk factors. Vigilance for potential new sources of contaminated air is required on units with high risk patients.

No significant financial relationships to disclose.
Invasive respiratory Aspergillosis is a treatable disease with early diagnosis and aggressive therapy
Authors: Cakir F. B. , Cakir E. , Berrak S. G. , Uyan Z. S. , Beker D. B. , Karakoc F. , Canpolat C. , Dagli E.
Published: March 2020

19632

Background: Invasive respiratory aspergillosis (IRA) is a fulminant infection in immunocompromised hosts. This study aims to evaluate the effectiveness of early screening of patients and the outcome of them during febrile neutropenia (FNP) episodes. Methods: Between 2003 and 2006, 212 FNP episodes were evaluated and the cases who are still febrile at their fifth FNP treatment were screened with computerized tomography (CT) of sinus, thorax and and other relevant sites. Results: Fungal infection rate was 15%, while IRA was detected in 22 patients. Thirteen of these patients were male. Fifteen patients had hematological malignancies, 6 had solid tumors and one patient had combined immunodeficiency and hemophagocytic lymphohistiocytosis. All patients had absolute neutrophil count of zero for 5 to 30 days (median 11.5 days). IRA cases were classified as definite (n:3), probable (n:7) and possible (n:12) according to European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group. Amphotericin B was administered emprically to all cases and continued as a single agent in 7 patients. Variable modifications with caspofungin, voriconazole or itraconazole were done in 11, 9 and 2 patients, respectively. At present, 7 patients are disease-free after completion of treatment, 6 patients are still on antifungal therapy, 4 patients were lost despite antifungal therapy and 5 patients died of underlying disease while in remission or with stabile disease for a median of 339 days (range: 13–1027 days). Therefore, our remission rate and overall survival rates are 83% and 60% respectively. Conclusions: Contrary to the previous reports, we suggest that IRA is a treatable disease with early diagnosis and aggressive antifungal therapy and it is worthwhile to screen FNP patients who are resistant to wide-spectrum antibiotics with CT for early intervention.

No significant financial relationships to disclose.
Symptom profile and clinical characteristics of metastases in metastatic renal cell carcinoma
Authors: Sawhney R. , Kabbinavar F. , Pantuck A. , Klatte T. , Zomorodian N. , Belldegrun A.
Published: March 2020

19638

Background: In the US, 39,000 new cases of renal cell carcinoma (RCC) will be diagnosed and 13,000 people will die of RCC, in 2006(1). While incidence has increased 126% since 1950 (2,3), little information is available regarding prevalence of symptoms & signs or metastases in patients presenting with metastatic RCC. Significance of such information is high as patients will be living longer, in this emerging era of targeted therapies for RCC. Method: Data were taken from prospective database of 1818 patients evaluated at UCLA with histologically confirmed RCC. From this 631 patients were identified with metastatic disease & surveyed at diagnosis. Data was obtained on matching variables, that included age, gender, ethnicity, smoking status, comorbidities, performance status, symptoms, site of metastasis & therapy. Results: 449 (71%) men, 182 (29%) women, were evaluated. Weight loss, hematuria, fatigue, flank pain, cough and musculoskeletal pains were the five most prevalent symptoms and signs. Of these patients, 557 (88%) were symptomatic with atleast one or more symptom on presentation and their presence lead to a diagnosis in 565 (90%) patients. In only 55 (8%) patients was metastatic RCC diagnosed incidentally. Most common metastatic site were the lungs 461 (73%), bones 200 (32%), followed by adrenals, non regional lymph nodes and soft tissue.Conclusion: In a large survey of metastatic RCC patients, weight loss, hematuria, fatigue, flank pain, cough and musculoskeletal pains were the five most prevalent symptoms and signs. Presence of atleast one or more of the above mentioned signs and symptoms led to a diagnosis in 90% of patients. Involvement of lungs and bones was most common at presentation. We believe that a better understanding of symptom and signs in patients with metastatic RCC, will lead to the development of better symptom assessment strategies, as well as early and thus cost-effective interventions. Especially in an era of increased disease control with targeted therapies.

No significant financial relationships to disclose.

[Table: see text]
Radiation pneumonitis (RP) in lung cancer patients treated with chemotherapy (CT) and thoracic radiation (TR): Retrospective analyses of patients treated at a comprehensive cancer center
Authors: Vishnu P. , Srinivasan S. , Heilbrun L. , Venkataramanamoorthy R. , Wozniak A. , Soubani A. , Gadgeel S. M.
Published: March 2020

19642

Background: Combined CT and TR is the current standard for locally advanced non-small cell lung cancer (NSCLC) and SCLC. Severe RP, an important adverse effect of TR, is reported in clinical trials to occur in 10% of patients receiving CT and TR. The rate in routine care may be higher as patients are not selected based on lung function. We conducted a retrospective study to assess the incidence of RP in lung cancer patients treated with CT and TR. Methods: Retrospective identification of patients who underwent combined modality therapy (concurrent or sequential CT and TR) for lung cancer (NSCLC & SCLC) at our cancer center between January 2001 and December 2004. Demographic features, RP incidence and grade (RTOG criteria), hospitalization rate and overall survival (OS) were assessed. Results: 51 patients who met the selection criteria were analyzed. The demographic features were - males 61%; Caucasians - 53%; African Americans - 39%; history of pulmonary disorder - 45%; NSCLC - 82%; CT - 62% received Cisplatin/Etoposide, while 24% received Carboplatin/Paclitaxel; 92% received concurrent CT and TR. The median dose of TR was 5940 cGy. 20 patients (39%) developed RP; 13 (25%) had grade = 3 RP. Median time to development of RP was 4.4 months. Rate of RP in females and males was 50% vs. 32% (p=0.25). Rate of RP in patients with pulmonary disorder at baseline was 52% vs. 29% in others (p=0.15). 1 year hospitalization rate was 75% and 42% in RP and non-RP patients (p=0.025). For all 51 patients, the median overall survival (OS) was 16.4 months (95% CI 11.8 - 23.3). Length of OS did not differ significantly (p = 0.36) between the 20 patients who had RP vs. the 31 who had no RP (median OS: 22.2 vs. 14.5 months, respectively). Conclusions: The RP rate in these 51 lung cancer patients treated off- protocol with CT and TR is higher than that reported in clinical trials. Despite higher morbidity in patients with RP (i.e., increased hospitalization), survival duration did not differ significantly based on RP status.

No significant financial relationships to disclose.
Multidimensional geriatric evaluation in elderly cancer patients and its relationship with age
Authors: Molina-Garrido M. , Guillén-Ponce C. , Carrato A.
Published: March 2020

19651

Background: Age is the major risk factor for the majority of patients with cancer. More than 50% of cancers occurs after the age of 60. Older patients are not simply old, but are geriatric patients because of interacting psychosocial and physical problems. As a consequence, the health status of old persons cannot be evaluated by merely describing the single disease or the group of age. We tested the performance of a new Comprehensive Geriatric Assessment (CGA) and its relationship with groups of age in cancer patients. Methods: Between June 2006 and December 2006, a total of 64 oncologic patients older than 75 years were approached to enrol in our study to analyze their functional, physical, mental, pharmacotherapeutic and socio-economic status and to correlate them to some groups of age: youngest-old (75 to 80 years-old), old-old (80 and 85 years-old) and oldest-old (older than 85 years). They were analysed Activities of Daily Living (ADL) measured by Barthel Scale, Instrumental Activities of Daily Living (IADL) measured by Lawton-Brody Scale, Grade of Fragility measured by Barber Scale, cognitive evaluation measured by Pfeiffer Test, and medication intake. A Chi Squared test was used for statistical analysis; p-value <0,05 was considered significative. Results: Sixty-four oncologic patients age > or = 75 years were recruited. Median age was 80.24 years (range 73.88 to 86.94). 51.6% female. Breast cancer was the most frequent diagnosis (30.2%), followed by lung cancer (19%). 29 patients (45.3%) were aged between 75 and 80 years old; 27 patients (43.5%) were between 80 and 85 years- old. There were statistic significative association between groups of age and Pfeiffer Test (p=0.037), Barber Scale (p=0.031) and medication intake (p=0.021). However, there was not a significative relationship between groups of age and Barthel Scale (p=0.052), Lawton-Brody Scale (p=0.2425), Cruz-Roja Scale (p=0,1485) or number of geriatric syndromes (p=0.129). Conclusions: This abstract reviews the findings regarding the correlation between a comprehensive geriatric assessment (CGA) and groups of age in older patients with cancer. Age per se must not be the only criterion for medical decision as it is not correlated to the health status of older cancer patients.

No significant financial relationships to disclose.
A brief measure of patients self-reported chemotherapy-related memory problem: Psychometric studies
Authors: Jean-Pierre P. , Morrow G. R. , Fiscella K. , Parrella M. , Kohli S. , Khanna R. , Jacobs A. D. , Issell B.
Published: March 2020

19655

Background: Memory is a central component of individuals’ functional systems of behavior, (i.e., cognition, emotionality, and executive functioning) that can be deleteriously affected by cancer treatment. It is important to identify and understand the effects of cancer treatment on memory in order to develop effective interventions to ameliorate these problems. This study involves structural and reliability analyses of a brief measure of chemotherapy-related memory problem to facilitate prompt and reliable preliminary assessments in oncology research and practice. Methods: Patients (N = 821) included in this analysis were part of a larger randomized clinical trial on cancer-related fatigue. These patients completed the Fatigue Symptom Checklist (FSCL) at four time points. Five items from the FSCL that assess memory problems were aggregated into a brief self-report memory problem measure (SRMP). Results: Reliability assessment of the SRMP revealed a Cronbach coefficient alpha of 0.90. The data was found suitable for latent structure analysis using various criteria: Kaiser-Myer-Olkin, Bartlett’s Test of sphericity, Kaiser’s (1959) simplest criterion test of γ >1, and the presence of item-correlation coefficients of r = .30. Principal components analysis showed one component with eigenvalue (γ) exceeding 1, that explained 72% of the variance. Subsequent reliability assessments of the SRMP revealed Cronbach coefficients alpha of 0.90 and above, all with a single component explaining 71.36% to 73.36% of the variances. Conclusions: The results supported the use of the SRMP as a reliable one- dimensional measure of cancer treatment-related memory problem. The SMRP could be used for preliminary assessment of possible underlying memory problems that might need further examinations. Studies to establish the construct validity of the SRMP are under way. Supported by NCI grant R25CA102618.

No significant financial relationships to disclose.
Dosimetric evaluation and comparison of small-field non-coplanar multi-arc radiotherapy (SMART) and intensity-modulated radiotherapy (IMRT) in treatment of tumor-related bronchial/superior vena cava (SVC) obstructions
Authors: Figura A. T. , Montebello J. , Wang J. , Zhang H. , Mayr N. , Gupta N. , Grecula J.
Published: March 2020

19668

Background: Rapid and cost-effective palliation is of great importance in patients with complications from lung cancer progression. To offer immediate treatment for a tumor-related obstructed bronchus or SVC, we have implemented the SMART technique which has been shown to be effective and safe in the primary and re-treatment of malignant bronchial/SVC obstructions. The purpose of this study was to determine if the dose coverage to the obstructed bronchus/SVC and normal tissue sparing achieved by SMART compare favorably to the lengthier and more expensive IMRT technique. Methods: Treatment planning CT’s from 9 patients with a bronchial obstruction and 1 with SVC were studied. The planning target volume (PTV) consisted of the clinical target volume (CTV = obstructed bronchus or SVC) plus a 1 cm margin. For SMART, a dose of 10 Gy in a single treatment to the target was computed using 18 MV photons with 5 to 8 non-coplanar arcs with field sizes ranging from 4 cm2 to 8 cm2. For a dosimetric comparison using the same planning CT, an IMRT plan with 5 to 9 fields using 6 MV photons with 95% CTV coverage was computed to deliver the same dose. Dose volume histograms (DVH), treatment delivery time based on monitor units (MUs), and mean doses to the CTV, PTV, heart, lungs, spinal cord, and total body dose were compared using Student’s t-test. Results: Pooled DVH analysis of SMART and IMRT showed that SMART provided slightly better, but not statistically significant, coverage of the CTV (97±1.1 vs. 92±5%) and PTV (94±2 vs. 89±5%). There was no difference in normal tissue sparing between SMART and IMRT with respect to the mean lung dose (9±7 vs. 9±7%), heart dose (7±10 vs. 3±5%), cord dose (37±13 vs.30±13%), and total body dose (8±4 vs.7±4 Joules). However, SMART delivery was faster requiring significantly less MUs compared to IMRT (1,284±65 vs.1984±90, p<0.002). Conclusions: IMRT showed no advantage over SMART in dose coverage of the CTV/PTV and sparing of critical normal tissues. Therefore, less complex planning and faster treatment delivery of SMART maybe clinically preferable for rapid palliation of critically ill patients with an obstructed bronchus/SVC.

No significant financial relationships to disclose.
Usefulness of frailty markers in the assessment of the health and functional status in older cancer patient referred for chemotherapy
Authors: Retornaz F. G. , Monette J. , Monette M. , Sourial N. , Wan-Chow-Wah D. , Batist G. , Bergman H.
Published: March 2020

19673

Background: In order to properly support clinical decisions, geriatric assessment (GA) is recommended for older cancer patients. However, the best form of GA remained unknown and recent studies demonstrated that usual GA tools may have a ceiling effect in detecting adverse outcomes to cancer treatment. Frailty has emerged as a concept characterizing cumulative declines across multiple physiologic systems, leading to increased vulnerability and risk of adverse outcomes. Consequently, the concept of frailty may represent a more sensitive way to better characterize health and functional status and to detect potential vulnerability to adverse outcomes in older cancer patients. The purpose of this pilot study was to explore the usefulness of frailty markers in older cancer patients. Methods: This cross- sectional study included 50 cancer patients, (70 years and older) referred to an oncology clinic for chemotherapy. Chronic diseases, IADL and ADL disabilities, and seven domains considered as frailty markers (nutrition, mobility, strength, energy, physical activities, mood and cognition) were assessed. Patients were classified into hierarchical groups based on the results of their assessment. Results: While 15 (30%) patients had at least one disability in IADL and 8 (16%) patients had at least one disability in ADL, 27 patients (54 %) were completely independent for IADL and ADL. Among those patients with no IADL nor ADL disability, 21 patients (42%) presented at least one frailty marker. In the whole cohort, 44 patients (88%) had at least one frailty markers. The most prevalent of the frailty markers were nutrition, mobility and physical activity (respectively 62%, 58% and 42%). Conclusion: Markers of frailty add substantial information to the usual GA tools in detecting potential vulnerability in older cancer patients. Additional studies are needed to determine if the addition of the frailty markers to the usual GA tools can help to better characterize the older cancer population and predict risk of toxicities and adverse outcomes due to cancer treatment.

No significant financial relationships to disclose.
Patient weight and event-free survival for children under 2 years of age at diagnosis with favorable histology Wilms tumor
Authors: Fernandez C. V. , Anderson J. , Breslow N. , Dome J. , Grundy P. , Perlman E. , Green D.
Published: March 2020

20002

Background: Over- and underweight have been associated with excess mortality in certain childhood cancers. The impact of the child’s weight at diagnosis on event-free survival (EFS) in favorable histology Wilms tumor (FH WT) is unknown. Methods: Patients with FH WT under 2 years of age at enrolment on NWTS-5 were included. This age group was analyzed by body weight in kilograms because body mass index (BMI) norms do not exist for individuals less than 2 years old. Outcomes by BMI for children older than 2 years of age with FH WT will be analyzed separately. CDC 2000 growth charts were used. Patients were stratified for risk based on stage and chemotherapy protocol [EE4A = vincristine/dactinomycin] [DD4A = vincristine/doxorubicin/ actinomycin]. A univariate analysis of the relationship of weight-for-age and EFS was calculated. A Cox proportional hazards model was fitted for EFS examining four subsets of weight-for-age by percentiles: a) less than 5%, b) 5–9.9%, c) 90–94.9% and d) more than 95% and adjusting for risk/treatment groups via stratification. Results: 594 patients met the study criteria. 567 had weights recorded. Median follow-up was 4.7 years. 10% of patients had a weight for age percentile of 5.6 or below and 10% had a weight percentile of 94.1 or above. A univariate analysis of the relationship of weight-for-age and EFS showed no relationship (p=0.40, log-rank test). A Cox proportional hazards model, stratified by risk/treatment groups, showed that low or high weight-for-age was not predictive of outcome (p=0.24). Conclusions: There was no evidence that low or high weight-for-age was predictive for EFS among patients less than 2 years old with FH WT. There were more patients with lower or higher weight than would be expected.

[Table: see text]

No significant financial relationships to disclose.
Effect of race on the quantity and timing of end-of-life discussions in pediatric oncology
Authors: Baker J. N. , Hinds P. S. , Zawistowski C. A. , Rai S. , Ma Y. , Althoff J. , Smalls A. , West N. , Kane J. R.
Published: March 2020

20004

Background: Clinicians and parents report that end-of-life (EoL) care discussions and decision making are complex, difficult and affected by personal, family, and disease and treatment factors. The influence of race on EoL discussions and decision making has not been carefully examined in a large pediatric oncology study. The purpose of this study was to assess if race (white, black, Hispanic) influenced the quantity or timing of end-of-life care discussions and decisions. Methods: This abstract represents a retrospective chart review leading to the creation of an EoL database of pediatric oncology patients at St Jude Children’s Research Hospital who died during the time period of July 01, 2001 to February 28, 2005. Eligibility criteria were oncologic diagnosis, and patient age less than 21.99 years of age at the time of death. After strict application of the eligibility criteria, a total of 380 patients met study inclusion criteria. The effect of race on the quantity and timing of EoL discussions and decision making was then analyzed from the database. All extracted data were validated by a different team member as was the accuracy of all entered data. The association of race with other factors was assessed using regression analysis and chi-squared testing statistics. Results: None of the following differed by race: the total number of EoL discussions before an EoL decision was made (p=0.58); the total time from the first such discussion to a specific EoL decision (p=0.23–0.68), the total time from the first discussion to the patient’s death (p=0.105), or having a DNR in place at the time of death (p=0.55). Conclusions: In this cohort of patients from a tertiary referral center, race is not a significant factor on the quantity and timing of EoL discussions and decision making in pediatric oncology patients.

[Table: see text]

No significant financial relationships to disclose.
Effects of multiple courses of oral gefitinib, topotecan, and cyclophosphamide in poor risk neuroblastoma
Authors: Donfrancesco A. , De Ioris M. , Jenkner A. , Ilari I. , De Sio L. , Castellano A. , Fidani P. , Serra A. , Cozza R. , De Laurentis C. , Dominici C.
Published: March 2020

20009

Background: Gefitinib (G) has shown potent inhibitory activity on neuroblastoma (NB) cell proliferation in in vitro models. Experimental data have also reported that the addition of G to cytotoxic drugs can increase in vitro and in vivo antitumor activity in several tumor models, but if this will translate in significant clinical benefits, with respect to survival, is still unclear. We evaluated the feasibility of administering an oral regimen including G combined with topotecan (TPT) and cyclophosphamide (CPA) in heavily pretreated pts with relapsed/resistant metastatic NB. Methods: Patients received oral CPA (50 mg/m2/day) followed by TPT (0.8 mg/m2/day) plus G (at the fixed dose of 250 mg/day) for 14 consecutive days in an outpatient setting. Courses were repeated every 28 days until progression, and response was evaluated every second course. Expression of EGFR mRNA in primary tumors was assessed by real-time RT-PCR. Results: Six pts (1M/5F), median age 5.4 years (range 4.1–8.2), were enrolled between October 2004 and October 2006. All pts were relapsed after high-dose chemotherapy and hemopoietic rescue with PBSCs. At the time of inclusion, 3 pts were in PR after 8 courses of second-line therapy, whilst 2 pts had achieved SD after 1 and 8 courses of second-line therapy, resp; 1 pt had PD right after PBSC rescue. Significant levels of EGFR mRNA were detected in 4/6 tumors. A median of 7.5 courses (range 1–24) per pt were administered. In 4 pts, the dose of TPT and CPA was reduced by 25% after the first course. After a median follow-up of 12 months (range 1–26), 1 pt is DOD at 15 months since the inclusion and 5 pts are alive, 1 in VGPR (26+ months) and 5 with SD (26+, 1+, 4+, 9+ and 18+ months). Median PFS is 7.5 months (range 1–26). Neutropenia grade 4 was observed in 4/6 pts; rash grade 2 in 2 pts, and hepatic (LFT increase) grade 3 toxicity in 1. Conclusions: The regimen was feasible and well tolerated in this series of heavily pretreated pts. PFS is encouraging, but deserves further evaluation and longer follow-up. Additional molecular studies are ongoing aimed at identifying the subset of NB pts most likely to benefit from the synergy between G and cytotoxic drugs observed in preclinical models.

No significant financial relationships to disclose.