bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of the role of FDG-PET imaging in malignant pleural mesothelioma (MPM)
Authors: Power D. G. , Farrelly C. T. , McDermott R. A. , O’Byrne K. J.
Published: March 2020

17113

Background: MPM is a rapidly progressive malignancy with a median survival of 6 to 9 months. Studies in non-small cell lung cancer, gastrointestinal stromal tumours, and breast cancer suggest that Positron Emission Tomography (PET) scanning may predict the clinical outcome of chemotherapy at an early stage of treatment. The role of PET in predicting and monitoring response to treatment in MPM is unclear. In this study we assessed if baseline and early interval PET scanning could be of benefit in MPM, correlating the results with standard Computerised Tomography (CT) assessment using the modified Response Evaluation Criteria In Solid Tumours (RECIST) of Byrne and Nowak. Methods: 10 patients with histologically proven MPM proceeded to baseline PET and CT scanning prior to chemotherapy. In 8 patients a second PET scan was performed within three weeks of commencing treatment. The following PET derived parameters were calculated: Standard Uptake Value (SUV)maximum, SUVaverage, PETvolume, and Total Lesion Glycolysis (TLG). Baseline SUVmaximum and early PET response was compared with CT response and survival. Results: Baseline SUVmaximum predicted subsequent CT response in the 10 patients studied. Four out of 5 patients with baseline SUVmaximum of <15 showed a subsequent partial response on CT, whilst the 5th patient had resolution of a pleural effusion. All 5 patients with baseline SUVmaximum of >15 had stable or progressive disease on CT. In contrast change in early SUVmaximum from baseline to 3 weeks did not predict subsequent CT response (Kappa value 0.07) in the 8 patients evaluated. Change in PET volume and TLG correlated with subsequent CT response (Kappa value= 0.80 for both). Only 1 patient with a partial response on % PETvolume and %TLG has died 14 months after commencing treatment. The other 3 patients are alive at 17+, 19+ and 20+ months. The 4 patients with stable or progressive disease using these parameters were deceased at 5, 6, 10, and 12 months respectively. Conclusion: PET may be useful in predicting and evaluating response to treatment in MPM. Furthermore, the results suggest that PET response may be a useful prognostic tool in this disease. It is important to use the appropriate PET derived parameters. Further study with a larger patient population is warranted.

No significant financial relationships to disclose.
Influence of histological type, smoking history and chemotherapy after 1st line on treatment outcome in advanced non-small cell lung cancer
Authors: Yamamoto N. , Itaya T. , Takahashi T. , Asai G. , Ebisawa M.
Published: March 2020

17118

Background: Primary endpoint of clinical trials of 1st line chemotherapy in advanced non-small cell lung cancer (NSCLC) is usually used over all survival. However, we know that 2nd line chemotherapy is prolonged survival time. Especially, Asian ethnicity, non-smokier and adenocarcinoma (Ad) were possible to be associated with survival in EGFR TKI such as gefitinib. Thus, we undertook this analysis to identify the prognostic factors of the progression free survival (PFS) and overall survival (OS) and to examine the effect of chemotherapy after 1st line in advanced NSCLC patients. Methods: We selected the patients who were received 1st line chemotherapy in the Shizuoka Cancer Center between October, 2002 and September 2005 and fullfilled following criteria: 1. stage IIIB or IV NSCLC, 2. no prior therapy for lung cancer, 3. chemotherapy regimen was CBDCA AUC 6 + Paclitaxel 200 mg/m2, 4. PS 0 or 1. Univariate and multivariate analyses were performed on possible porgnostic factors such as gender, PS, smoking history, histology (adenocarcinoma or other), and stage. Results: A total of 98 patients (35 females, median age 61 years [range 340–78], 74 adenocarcinomas, 73 smokers, 56 PS 0) fullfilled above selection criteria. 71 (78%) in these patients received 2nd line chemothrapy (gefitinib 44%, erlotinib 4%, and docetaxel 48%). Median-PFS and MST was 4.9 months(m) and 16.1m. PFS was not significant difference in smoking history (M-PFS: smoker 5.0m, non-smoker 4.4m) and histlogical type (Ad 4.9m, others 4.7m). However, OS was significant diference in each factor(2 yr survival rate: smoker 61%, non-smoker 17%, p = .0001, Ad 39%, others 8%, P = .0001). Multivariate analysis in 71 patients received 2nd line chemotheraoy revealed that treatment of EGFR TKI was only independent predictors of OS. Conclusions: OS of non-smoker or adenocarcinoma patients was very excellent. the usage of EGFR TKI was associate with prolongation of these OS.

No significant financial relationships to disclose.
The use of statins and the effect on survival in patients with small cell lung cancer
Authors: Hanbali A. S. , Urbaez Duran E. , Wang D. , Jankowski M. , Syed A. , Farhan S. , Chapman R.
Published: March 2020

17121

Background: Hypercholesterolemia is one of the most common morbidities in United States. Statins have been proven as effective cholesterol-lowering agents and have been widely used in this country. They have been reported reducing the incidence and risk of various cancer types. However, the impact of using statins on the survival of patients with diagnosed small cell lung cancer is unknown. Methods: A retrospective study involved a cohort of 282 patients with diagnosed small cell lung cancer. Patients were identified from the Tumor Registry at Henry Ford Health System between January 1995 and December 2002. Electronic medical records of these patients were reviewed. Statistical analyses were performed and stratified for statin users versus non statin users. Results: Out of 282 patients, there were 73 patients with hypercholesterolemia, 37 of them were statin users at the time of their small cell lung cancer diagnosis. Average age was 65 (range 34–87) years for non statin users and 69 (range 52–85) years for statin users. Median survival of 282 subjects was 7.37 months. After stratifying for statin use, the median survival of statin users was 8.66 months while the median survival of non statin users was 7.17 months (p = 0.29). Conclusion: Though slightly prolonged median survival in statin-users was observed, no survival benefit is demonstrated from this patient population. Factors that may have contributed to this result will be further discussed. With the trend of an increase in median survival among statin users, whenever possible, continuation of statins as co-morbidity management may still benefit patients with small cell lung cancer, during their receiving standard anti-tumor therapies.

No significant financial relationships to disclose.
A preclinical survey on the efficacy of NSC-290205 in combination with doxorubicin (ADR) in Lewis lung carcinoma (LLC)
Authors: Papageorgiou A. , Stergiou E. , Boukovinas I. , Geromichalos G. , Stergiou I.
Published: March 2020

17131

Background: NSC-290205 (A) is a hybrid synthetic antitumor ester, which combines a D-lactam derivative of androsterone and nitrogen mustard. Studies on modified steroidal esters of carboxylic derivatives of N,N-bis(2-chloroethyl)aniline, have shown that they exhibit reduced toxicity and increased antitumor activity and specificity. In this study we investigated the antitumor activity of compound A in combination with ADR (AHOP) in comparison with standard CHOP regimen. Methods: C57Bl mice were used for the antitumor evaluation of AHOP/CHOP. Experiments were initiated by implanting the tumor. LLC cells (purchased by NCI, Bethesda, USA) were implanted intramuscularly into the right hind leg as a suspension of 7 × 106 cells in 0.1 ml. The antitumor activity was assessed from the inhibition of tumor growth by volume in cm3 and the oncostatic parameter T/C % according to the protocol of experimental evaluation of antitumor drugs of the NCI, USA. Treatments were given as a single dose (D) on day 1, intermitted dose (D/2 × 3) on days 1, 5, 9 or consecutive dose (D/4 × 9) on days 1 through 9. Results: Treatment with A or cyclophosphamide produced almost equal borderline activity. Moreover, both CHOP and AHOP regimens showed significant and comparable antitumor effect (p < 0.05 by the Wilkoxon test). AHOP caused the maximum effect inhibiting the tumor growth by 67.7% and T/C values of 270%. CHOP was less effective producing 54.8% tumor inhibition and T/C values of 238%. Conclusions: It is very likely that the D-lactamic steroid (androstan) alkylator for A, containing the -NHCO group, combined with ADR, which intercalates between base-pairs, is the explanation for higher activity of AHOP vs. CHOP. This significant effect of NSC-290205 with the anthracycline adriamycin on LLC adds to NSC-290205 advantage for further clinical development.

No significant financial relationships to disclose.
Phase II trial of oxaliplatin and gemcitabine in patients with malignant pleural or peritoneal mesothelioma
Authors: Boyar M. S. , Hesdorffer M. , Taub R. N.
Published: March 2020

17133

Background: A prior phase II trial of oxaliplatin and gemcitabine in malignant pleural mesothelioma reported activity with a 40% partial response rate and stable disease in 24% of 25 previously untreated patients (Schutte W. et al., Clin Lung Cancer 2003;4:294). This trial was designed to further evaluate the efficacy of oxaliplatin and gemcitabine in patients with malignant pleural or peritoneal mesothelioma. Methods: Patients with histologically-confirmed malignant pleural or peritoneal mesothelioma not amenable to curative surgical treatment are eligible for enrollment on this single-institution phase II trial. One prior chemotherapy regimen is allowed, including pemetrexed with a platinum compound or gemcitabine. Presence of at least one radiologically-measurable lesion that has not been previously irradiated is required. Gemcitabine 1000 mg/m2 IV over 90 minutes is administered followed by oxaliplatin 100 mg/m2 IV over 2 hours on day 1 of a 14-day cycle. Treatment is continued for at least 6 cycles unless unacceptable toxicity or disease progression occurs. The primary outcome is to evaluate efficacy as measured by tumor response rate. The sequential two-stage design allows for enrollment of a total of 29 patients if 3 of 18 patients enrolled in the first stage have at least a partial response. Results: Ten eligible patients have been enrolled thus far and 6 are evaluable for response. Sites of disease include pleural (3) and peritoneal (3), and histologic subtypes are epithelioid (5) and sarcomatoid (1). Four patients had received prior chemotherapy. A total of 42 cycles have been given with a median of 8 cycles per patient. There are no partial or complete responses. Four patients have had stable disease for at least 4 months. Two patients with stable disease had received prior pemetrexed/gemcitabine or pemetrexed/cisplatin. Frequently observed toxicities include grade II fatigue, neuropathy and upper gastrointestinal dysmotility. Conclusion: This regimen of gemcitabine and oxaliplatin may provide disease stabilization in a subset of patients with malignant pleural and peritoneal mesothelioma, including those who have received prior chemotherapy. The regimen is well-tolerated. This study remains open to accrual.

No significant financial relationships to disclose.
Outcomes of advanced stage non-small cell lung cancer (NSCLC) patients reexposed to platinum-based chemotherapy upon progression
Authors: Souza P. H. , Rodrigues A. N. , Dienstmann R. , Small I. A. , Roriz W. , Martins R. G. , Zukin M. , Ferreira C. G.
Published: March 2020

17136

Background: Platinum-based chemotherapy (PtCT) is the standard 1st-line treatment for advanced stage NSCLC patients. Nearly all patients (pts) that respond to 1st-line CT will relapse and some of them will be candidates for 2nd-line CT. There is no consensus definition of sensitive or resistant pts to PtCT and there are conflicting results about the relationship between response to prior PtCT and response to a 2nd-line reexposure. The aim of this study was to evaluate the outcomes of a subset of pts considered sensitive to platinum, who were reexposed to a PtCT regimen as 2nd-line CT. Methods: Based on a criterion of disease progression > 6 months of completing 1st-line as a hallmark platinum-sensitivity, pts were retrospectively selected. We reviewed the outcomes of 11 advanced NSCLC pts (stages IIIB or IV) treated between Jan 2000 and Jun 2005 at 1st-line with a PtCT (cisplatin or carboplatin combined to etoposide) and who upon progression were reexposed to a regimen of Carboplatin plus etoposide. Pts were evaluated for overall (OS) and progression-free survival (PFS) after 1st- and 2nd-line CT by Kaplan-Meyer method. Results: There were 6 women (54.5%) and 5 men (45.5%). Median age was 62 (range 49–78) and adenocarcinoma was the most prevalent histology (54.5%). At 1st-line CT, 6 patients (54.5%) were stage IIIB and ECOG PS 0/1 were 36.4 and 63.6%, respectively. The median number of cycles per patient was 6 (range 2–8) at 1st-line and 4 (range 2–4) at 2nd-line treatment. With a median follow-up of 29 months, there were 4 deaths (36.5%) with a median OS of 49 months (CI 95%; 29.38–68.62). The median PFS after first-line was 17 months (IC 95%; 13.87–20.13). To date, 7 pts have progressed after 2nd-line CT with a median PFS of 8 months (IC 95%; 5.92–10.09). Conclusions: This subset of pts with longer progression-free interval (> 6 months) after 1st-line PtCT seems to remain sensitive to platinum compounds upon disease progression. Despite the high proportion of stage III in our sample, based on the long DFS and OS observed, it seems that this population has a more favorable biology than the general population with NSCLC. Further studies, in particular pharmacogenetic analyses, are needed in order to better characterize and treat this population.

No significant financial relationships to disclose.
Prognostic factors for patients with lymphoma requiring intensive care
Authors: Scheliga A. , Vieira F. M. , Spector N. , Romano S. , Salluh J. I. , Bello R. D. , Soares M.
Published: March 2020

17519

Background: Prognosis of patients (pts) with hematological malignancies (HM) in the intensive care unit (ICU) seems to be improving, despite different biological behaviors and outcomes. The study of homogenous groups of pts might provide useful clinical insights. The aim of this study was to evaluate the outcomes of critically ill patients with lymphomas (CIPL). Methods: During 66 months, all consecutive CIPL admitted to an oncologic ICU were studied. Variables collected were: age, gender, performance status, type and status of lymphoma, neutropenia, infection at admission, use of mechanical ventilation (MV), the Acute Physiology and Chronic Health Evaluation (APACHE) II score, comorbidities and number of acute organ failures (AOF). Variables selected in the univariate analysis (p < 0.25) and those clinically relevant were entered in a multivariable logistic regression analysis [results expressed as odds-ratios (OR), 95% confidence interval (CI)]. The end-point was hospital mortality. Results: A total of 120 CIPL were studied. Mean age was 51 ± 20 years and 54% were males. APACHE II was 19 ± 7 points. Diagnoses were High Grade Non-Hodgkin’s Lymphoma (77.5%), Hodgkin’s disease (17.5%) and Low Grade Non-Hodgkin’s Lymphoma (5%). Reasons for ICU admission were severe sepsis (62%) and acute respiratory failure (22%). During ICU stay 90% pts received MV, 71% vasopressors and 27.5% dialysis. Twenty-three (19%) pts had neutropenia. End-of-life decisions were implemented in 31% pts and all of them died at the ICU. The ICU and hospital mortality rates were 53% and 67% respectively, with no difference among the groups of lymphomas (p = 0.877). Variables identified in the multivariate analysis were: age [OR = 1.03 (95% CI = 1.01–1.06)], male gender [3.72 (1.27–10.90)], uncontrolled disease [OR = 6.28 (1.80–21.95), for pts with newly diagnosed disease and OR = 5.33 (1.45–19.47), for those with recurrence/progression, sepsis [OR = 5.31 (1.62–17.37)] and AOF [OR = 2.35 (1.53–3.61)]. Conclusions: Higher age, male gender, the severity of organ failures, sepsis and disease status were the main adverse factors. Type of lymphoma and neutropenia had no impact in the outcome. The appropriate use of such easily available clinical characteristics may avoid forgoing intensive care for lymphoma pts with a chance of survival.

No significant financial relationships to disclose.
Long-term outcomes after laparoscopic splenectomy for splenomegaly
Authors: Brethauer S. A. , Chalikonda S. , Dan A. , Nfonsam V. , Goncalves C. , Rosenblatt S. , Lichtin A. , Walsh R. M.
Published: March 2020

17527

Background: Numerous studies have demonstrated the feasibility of laparoscopic splenectomy (LS) for splenomegaly. There is little published data on the long-term efficacy of LS. The aim of this study is to determine long-term outcomes following LS for splenomegaly. Methods: Retrospective review of patients undergoing LS between 8/95 and 5/05. Splenomegaly was defined by CT criteria of craniocaudal length > 17 cm. Preoperative diagnoses included lymphoma in 13 patients (20%), leukemia in 15 (23%), autoimmune hemolytic anemia in 3 (5%) and other hematologic disorders in 8 (12%). 26 patients (40%) had no definitive diagnosis prior to splenectomy. Patients with ITP were excluded. Patient demographics, operative indications, operative morbidity and mortality, pathology, pre- and postoperative hematological indices were collected. Follow-up was obtained from patient records and telephone interviews. Results: 311 patients underwent LS during the study period. 65 patients underwent LS for splenomegaly. The mean age was 59 and 62% were male. There were no operative deaths. 7 patients (11%) were converted from LS to open. There were 9 (14%) major complications including 4 re-operations (3 for bleeding), 3 portal vein thromboses, 1 intra-abdominal abscess and 1 postoperative hemorrhage managed non-operatively. Thirty-two patients underwent LS primarily for diagnostic purposes. Nine had an existing hematologic disease and LS was performed to evaluate splenic involvement. LS confirmed a diagnosis in 19 (59%) patients including 11 lymphomas (34%). Thirty-three patients underwent LS primarily for treatment of either symptoms (33%) or cytopenias (66%). LS effectively treated mass symptoms in all patients. Among all patients 33 (51%) had associated cytopenias. At median f/u of 20 months 15 (45%) patients had no recurrence of cytopenias, 15 (45%) patients required further treatment and 3 were lost to follow up. One responder (7%) died of lymphoma 3 months after surgery without recurrence of cytopenia. The 15 non-responders had progression of disease requiring chemotherapy and transfusions and 9 (60%) died a median of 6 months after LS. Conclusions: LS is a valuable diagnostic and therapeutic tool for patients with splenomegaly and provides durable treatment for splenomegaly-associated cytopenias.

No significant financial relationships to disclose.
An initial analysis of an allele-specific quantitative PCR (Q-PCR) assay which detects minimal residual disease (MRD) in the peripheral blood of follicular lymphoma (FL) patients
Authors: Theriault T. , Kautz N. , Mason K. , Ingolia D. , Denney D. W.
Published: March 2020

17541

Background: MyVax Personalized Immunotherapy is an active immunotherapy that targets the idiotype of surface immunoglobulin (Ig) on malignant B cells and is currently in a pivotal Phase 3 trial. Idiotype vaccines have shown promising results in early phase clinical trials. The monitoring of circulating tumor cells in peripheral blood lymphocytes (PBLs) may provide important information regarding disease status and response to therapy. A standard method of assessing MRD in FL is by PCR amplification of the t(14:18) translocation at the major breakpoint region (MBR) locus. Studies have shown that 35–50% of FL tumors are not detected by the MBR assay. Circulating non-malignant cells that carry the t(14:18) translocation may complicate MBR analysis. We have developed an allele-specific oligonucleotide (ASO) Q-PCR assay that detects unique Ig heavy chain sequence. This patient-specific ASO assay has the ability to monitor tumor in PBLs of all patients. Methods: Three TaqMan assays were performed on each sample analyzed: 1) ASO; 2) MBR; 3) albumin. The MBR and albumin assays were standard for all patients. The ASO assay was developed for each patient based on amplification using patient-specific primers and TaqMan probes that span the CDR2/CDR3 region of each patient Ig heavy chain. The Ig heavy chain sequences identified during the production of MyVax Personalized Immunotherapy were used to develop patient-specific primers and probes. MBR and ASO counts were normalized using the results of the albumin assay. Assays were performed on DNA samples isolated from PBLs collected before and 6 months after chemotherapy and following MyVax Personalized Immunotherapy. Results: Q-PCR data were grouped into MBR positive and MBR negative sets. We were able to monitor tumor-specific cells present in peripheral blood by the ASO assay in all patients. ASO values appear to correlate with MBR values. Both the ASO and MBR assays allowed detection of 1 tumor cell in 104 to 105 PBLs with reaction efficiencies of 1.80 or higher. Conclusions: The ASO assay is broadly applicable for detecting MRD in both MBR positive and MBR negative FL patients.

[Table: see text]
Autologous stem cell transplantation (ASCT) in AL amyloidosis: Feasibility outside national amyloidosis referral centers and proposal for simpler pre-transplant staging
Authors: Jain N. , Pasquini M. , Paul M. , Hari P.
Published: March 2020

17545

Background: Single center data from national amyloidosis referral centers suggest that high dose melphalan based ASCT is an effective upfront treatment strategy for AL amyloidosis. Absence of published randomized control trials, referral bias and center experience make generalizability of this data difficult since data from outside of major referrals centers is limited. Pre-transplant staging is complicated by the profusion of articles describing various adverse risk factors. Methods: Retrospective review of bone marrow transplant database at our institution was conducted. All patients with AL amyloidosis who underwent ASCT were included in the study. We stratified patients based on International Staging System (ISS) for multiple myeloma. Organ and hematological response were assessed using 2005 consensus guidelines. Results: 13 patients (6 males) underwent ASCT for AL amyloidosis with risk adapted high dose melphalan dosing (melphalan mg/m2 100 (n = 1), 150 (n = 8) and 200 (n = 4)). Median age of the patient population was 53 years (range 31–75 years). Organ involvement was as follows - single organ = 6, 2 organs = 4 and 3 organs = 3. 4 patients had cardiac amyloidosis. 100 day transplant related mortality (TRM) was 15.3%. Overall survival was 84 % (95 % CI 51–96%) @ 1 yr and 75% (95% CI 38–91%) @ 2 yrs. Median follow up was 18 months. No deaths were observed >17 months post-transplant. 45 % patients had organ response. Complete hematological response was observed in 45 % patients. Mean duration of peri-transplant hospital stay for ISS stage I, II and III were 20.5 days (n = 2), 23.3 days (n = 9) and 29 days (n = 1) respectively. Number of deaths observed in ISS stage I, II and III were 0 (0/2), 2 (2/9) and 1 (1/1) respectively. Conclusions: Autologous stem cell transplant (ASCT) for AL amyloidosis is a feasible, effective and safe procedure outside of major national referral centers. Pretransplant stratification of amyloidosis patients using ISS for multiple myeloma indicated a trend towards longer peri-transplant hospital stay and mortality with increasing ISS stage. This hypothesis needs to be tested in larger studies.

No significant financial relationships to disclose.
Prognostic value of hemoglobin in natural killer cell lymphoma
Authors: Xiao J. , Lin T. , Cao Y. , Fu X. , Guo C. , Zhai L. , Guan Z.
Published: March 2020

17557

Background: Natural Killer (NK) cell lymphoma is a group of increasingly recognized but poorly defined disease entities. This study investigated its clinical features and prognostic factors for southern China population. Methods: Patients with pathologically confirmed NK cell lymphoma in one center since 1999 to 2004 were included. Central histological and immunohistochemical review was undertaken to every case. The major study endpoint was overall survival. Survival curves were estimated by the Kaplan-Meier method. Detailed clinical, pathological and laboratory data were included in univariate analysis and statistically significant factors in univariate analysis were then included in multivariate analysis. Results: Totally 64 eligible patients were identified. Of these, 59 patients were extranodal NK cell lymphoma nasal type, 3 patients were aggressive NK cell lymphoma and 2 patients were blastic NK cell lymphoma. From the basic analysis, 47% of the patients had stage I disease, 42% were stage II, 11% were stage III or IV. B-symptoms were present in 39%. 73% of these patients had International Prognostic Index (IPI) 0 or 1. Before treatment, 25% complicated with anemia. As to the therapy, 38% received chemotherapy alone, 3% received radiotherapy alone and 59% received a multidisciplinary therapy. After initial therapy, 59% achieved CR, 22% achieved PR and 19% were refractory disease. With a median follow-up duration of 20 months, the median overall survival was 28 months (95% CI: 10, 45). Hb lower than 110 g/l before treatment was statistically significant in multivariate analysis (p = 0.031). Presenting B-symptoms and ECOG PS score higher than 1 were also independent prognostic factors (P = 0.001 and 0.006 respectively). Conclusions: The outcome of patients with NK cell lymphoma was poor even for Stage I or II cases. Our data suggested Hemoglobin < 110 g/l had more prognostic value than IPI and Ann Arbor staging system for NK cell lymphoma in southern China, but it needs further confirmation.

No significant financial relationships to disclose.
Supportive and unsupportive behaviors of friends and families as experienced by cancer patients
Authors: Grange C. , Matsuyama R. , Lyckholm L. , Smith T. J.
Published: March 2020

18625

Background: Interpersonal support can help individuals manage stressors associated with cancer diagnosis and treatment. This study reveals cancer patients’ experiences with supportive and unsupportive behaviors of friends and families. Insufficient or inappropriate social support can negatively impact coping, quality of life and other patient outcomes. Methods: Eleven focus groups were conducted with 39 African-American and Caucasian cancer patients recruited from a university-affiliated cancer clinic, using established qualitative methodology. Data analysis included whole group analysis with a team of 4 researchers. Atlas Ti software was used to validate coding and establish intra-rater and inter-rater reliability. Results: Supportive behaviors included practical assistance (e.g., providing meals), family providing housing and daily care, family/friends who listen, prayer, and a social context that demonstrates positive attitudes. Unsupportive behavior included limitations of independence and withdrawal from patients due to fear or discomfort, as well as having to provide emotional support to family or friends. African-American participants were more likely than Caucasian participants to report family or community resources available for daily care and expressed greater concern about limitations to independence. Conclusions: Findings have implications for interventions to improve the quality of support provided to cancer patients from their caregivers and communities. Results can be used to inform family, friends and caregivers about the types of support valued by patients.

[Table: see text]

No significant financial relationships to disclose.
Doxorubicin and DTIC in organ transplant recipients with metastastic soft tissue sarcoma
Authors: Schoeler D. , Hildebrandt B. , Bachmann U. , Reichardt P.
Published: March 2020

19502

Background: The development of cancer in organ transplant recipients is well known. Depressed immunosurveillance induced by the use of immunosuppressive agents for prevention of rejection is a causative factor. Kaposi’s sarcoma (KS), non-Hodgkin lymphoma and nonmelanoma skin cancers are more than 20-fold increased than in general population, EBV, HSV and HHV-8 seem to be causative. Other soft tissue sarcoma (STS) than KS are extremely rare post-organ transplantation tumours. Methods: Due to the fact that there is no “standard therapy” in organ transplanted STS patients we studied the feasibility, toxicity and response to a chemotherapy with doxorubicin (75 mg/m2, d1) and dacarbacine (DTIC, 300 mg/m2, d1–4). Two patients with metastatic disease (histology: poor differentiated uterine stromal sarcoma, poor differentiated malignant peripheral nerve sheath tumour, each n=1) were treated with up to 6 cycles of therapy. Results: One patient achieved a partial remission and dramatic improvement in life quality, the other patient achieved a stable disease after 2 cycles of therapy. Conclusions: Therapy with doxorubicin and DTIC is feasible in organ transplant recipients. Handling of the immunosuppression while chemotherapy is unproblematic.

No significant financial relationships to disclose.
A single team experience of adjuvant radiation therapy in adults with intermediate or high-grade limb soft tissue sarcoma
Authors: Merimsky O. , Soyfer V. , Kovner F. , Meller I. , Kollender Y. , Issakov J. , Inbar M. J.
Published: March 2020

19509

Background: Limb Soft tissue sarcomas (STS) are currently treated with limb sparing surgery (LSS) followed by radiation therapy (RT). This paper summarizes a one-team experience with homogenous population of adult patients, with intermediate or high grade STS confined to a limb, who were approached by LSS and postoperative RT. Methods: From October 1994 through October 2002, 133 adult patients (75 males, 58 females, age range 18–88 years, median 54) with biopsy-proven intermediate or high-grade limb STS were approached by LSS followed by RT. Their files were retrospectively reviewed for treatment outcome: local control, RT side effects, and time to progression. Tumor site was classified according to its proximal border. STS that involved the arm and the upper axilla was classified as axillary STS. Results: RT related toxicity was manageable, with a low rate of severe effects. At 4-year median follow up, there were 48 recurrences of any type, 23 of isolated local failure, and 35 of systemic spread w/o local failure. DFS and OS were influenced by disease stage II versus I, primary site in the upper limb versus lower limb, MPNST versus other types, induction therapy versus no induction, adequate resection Vs marginal resection or involved margins, and good response to induction therapy versus bad response. DFS and OS were Patient’s age and sex, tumor depth, acute or late toxicity of RT, or the interval of time between the date of definitive surgery and the start of RT did not affect DFS and or OS. Conclusions: The RT protocol is applicable in the era of complicated, expensive and time-consuming 3-D therapy. Our results of LSS + RT in adults with limb HG STS are satisfactory.

No significant financial relationships to disclose.
Excellent survival of pediatric dermatofibrosarcoma protuberans in Taiwanese
Authors: Chien C. , Chang Y. , Lin D. , Lin Z. , Yang R.
Published: March 2020

19512

Background: Pedicatric dermatofibrosarcoma protuberans (PDFSP) was a rare disease. We reported our institutional experience with PDFSP treated from 1977–2002. Methods: Twelve patients with PDFSP diagnosed before age 18 years were treated in our institute from 1977–2002 according to institutional cancer registry. After approved by institutional research ethic committee (ClinicalTrials.gov Identifier: NCT00173355 ), active patient contact and linkage with National Residency Registry was done to survey the disease status. Results: There were 6 boys and 6 girls in this study. The median age at diagnosis were 16 years (range: 3 months ∼18 years). The disease sites were diverse, from scalp to knee. Nine of them underwent wide excision in our hospital for their primary disease; the other 3 patients underwent wide excision in our hospital for local recurrent disease. None of them underwent neoadjuvant or adjuvant therapy. All of them had low grade T1a (≤ 5cm in size, superficially located) disease except T staging was not available in two patients. Negative margin was obtained in all in the operation of our instituion except close margin in one patient, who had uncontrolled recurrence and died of progressive disease later. The clinical follow-up (FU) period range from 1 to 214 months (median: 30). Active patients contact via telephone followed by twice postcard invitation was done. No evidence of disease (NED) was revealed by medical FU for three patients and by telephone FU for three patients. For the remaining six patients who had no response after telephone and postcards contact, data from linkage with National Residency Registry was used. Death was noted in one patient and aliveness was noted in five patients (all of them were NED in their last FU in our hospital). The 10-year/15-year progression free and overall survival rates were 100%/75% and 100%/83% respectively without obvious complications. Conclusion: The prognosis of PDFSP in Taiwanese was excellent when adequate surgical margin was obtained.

No significant financial relationships to disclose.
Late relapse associated with CEP 17 polysomic breast cancer
Authors: Theobald L. J. , Dobin S. , Beeran S. , Miltenburg D. , Rajab H. , Song J. , Boyle T.
Published: March 2020

20011

Background: The clinicopathologic features associated with chromosome enumeration probe 17 (CEP 17) polysomy by fluorescence in situ hybridization (FISH) are not well defined. CEP 17 polysomy is frequently encountered in assessing Her-2neu amplification, which has become an important adjuvant therapeutic target. One mechanism to increase Her-2neu gene copy is polysomy. In this analysis the prognostic and predictive factors associated with CEP 17 polysomy are compared to similar factors in Her-2neu gene amplification. Methods: All cases of Her-2neu gene amplification and CEP 17 polysomic breast cancers from 2000 to present were abstracted. The polysomy group was defined as at least 3 gene copies and was further subdivided into two groups; 3–4 copies and ≥ 5 copies. This resulted in 193 cases of invasive breast cancer, which became the study cohort. Polysomic status and her-2neu gene amplification was compared to age, estrogen receptor (ER), progesterone receptor (PR), grade, tumor size, cell type, mitotic rate, nodal status, number of positive nodes and relapse. Descriptive statistics were used for categorical variables. The χ2 test was used to compare each clinicopathologic factor. Results: Both the ER and PR status was significantly different in the 3 groups. For the Her-2neu amplified, the polysomic 3–4, and the polysomic ≥ 5, the ER positive status was 53%, 67% and 81%, respectively (p = .012). Histologic grade, tumor size and nodal status were not significantly different between groups. Lobular pathology was present in 15% of the polysomy ≥ 5 group, 8% of the polysomy 3–4 group and 1.7% of the amplified group and this difference was significant (p = .03). Relapse disease status was significantly more frequent in the polysomy ≥ 5 group (18.5%) compared to the amplified group (2.6%) (p = .007). Within the relapsed group the median time to relapse was 4 years for the amplified patients versus 12 years and 10 years for the polysomic patients. Conclusion: The incidence of CEP 17 polysomy varies in the literature from 10–50% depending on definitions. Our study is unique in that we divided the polysomic group into 3–4 copies which can be complicated by proliferative activity versus ≥ 5 copies. A significant association between relapse and polysomic breast cancer is described in our dataset.

No significant financial relationships to disclose.
Transient transcriptional response to low-dose ionizing radiation in humans undergoing IMRT
Authors: Goldberg Z. , Berglund S. R. , Dai J. , Santana A. , Rocke D. M.
Published: March 2020

20018

Background: As intensity modulated radiation therapy techniques are increasingly utilized to treat cancer, the area of normal tissue exposed to ionizing radiation is increasing. The biologic risks associated with this normal tissue low dose exposure (LDIR) are fundamentally unknown and of concern to cancer survivors following therapy. Current modeling for health regulations presupposes a linear, no-threshold model of radiation effects, which estimates the effect and risk at low dose by extrapolation from measured effects at high doses. Cell culture models of ionizing radiation (RT) exposure show variable effects, not consistent with a linear dose-response relationship. We therefore undertook the first study to our knowledge of transcriptional effects of LDIR over time in vivo in solid tissue in humans. Methods: Tissue was collected at pre-RT, 3, 8, and 24 hours post-IR at sites receiving 10cGy. Transcriptional response at 3 and 8 hours were compared to the 0 and 24 hour time points. If transcripts are up regulated or down regulated at 3 and 8 hours compared with 0 and 24 hours, we have detected a transient response. The method of Rocke (2005), which was designed to detect differentially expressed gene groups using the responses of multiple probe sets corresponding to gene groups, was used to allow us to test whether there is differential expression for each patient separately, as well as for all the patients together. Results: Significant (p < 0.05) transient up regulation was shown in zinc finger proteins, keratins, BMP receptors, BAG, cyclins and BCL 6. Down regulation was detected in TNF, protein disulfide isomerase, interleukins, heat shock proteins, and S100. Nine gene groups did not show significant change; however, the number of significant gene groups (11) far exceeds the number expected by chance (2). In most cases in which a gene group was shown to be transiently altered, the tests of individual patients showed that most or all of the individuals also had differential expression of the same type. Conclusions: We have shown that it is possible to detect transient responses to LDIR in vivo in humans, and have identified eleven gene groups that demonstrate transient changes, as measured by a statistically principled analysis method.

No significant financial relationships to disclose.
Relationship between survival and PET measurements of tumour blood flow, in patients with metastatic colorectal cancer
Authors: Charnley N. G. , Azeem S. , Gupta N. , West C. , Swindell R. , Bruce J. , Price P.
Published: March 2020

20021

Background: There are conflicting reports on the relationship between tumour blood flow and patient survival. Poor flow is associated with tumour hypoxia and has been associated with a poor outcome (Lehtio et al 2004;Int J Radiat Oncol Biol Phys:59, 971–982). However, good flow is associated with angiogenesis which drives tumorigenesis, and has also been linked with a poor prognosis (Hermans 200 Int J Radiat Oncol Biol Phys:57, 1351–6). In this study, we examined the relationship between PET measurements of blood flow in liver metastases, and survival, in patients with colorectal cancer. Methods: Thirty seven patients with metastatic colorectal cancer, with a range of previous treatments, were studied. Regional perfusion was measured in liver metastases using H2[15O] or C[15O]2 PET. Blood flow was correlated with overall survival from the time of PET scan. Relationship between outcome and flow was analysed separately for patients with 1 or >1 metastatic sites; a recent meta-analysis of patient with metastatic colorectal cancer showed number of metastatic sites to be an independent prognostic factor (Kohne et al 2002; Ann Oncol. 13, 308–317). Results: There was no significant relationship between survival and metastasis blood flow when the data were taken as a whole. However, when the data were corrected for number of metastatic sites, there was a trend for high flow to be associated with shorter survival (p = 0.063). Specifically, for patients with multiple metastatic sites, median survival times for patients with high flow (n = 9) was 171 days [95% CI 25–317] compared with 441 days [95% CI 12–870] for patients with low flow (n = 7) (p = 0.026). Conclusions: In patients with multiple sites of metastasis, high tumour blood flow is a poor prognostic factor. This may be due to angiogenesis, which promotes tumorigenesis.

No significant financial relationships to disclose.
Hereditary breast/ovarian cancer families: The impact of mutation prediction models on BRCA1/2 mutation screening costs
Authors: Capalbo C. , Ricevuto E. , Marchetti P. , Adamo B. , Adamo V. , Vestri A. , Frati L. , Screpanti I. , Gulino A. , Giannini G.
Published: March 2020

20027

Background: The considerably high costs of BRCA1/2 mutation screening together with the expanding request for inherited breast/ovarian cancer genetic counselling and testing, dictates the need for more accurate selection of the appropriate candidates for analysis. The aim of the present study was to evaluate, the impact that careful selection of appropriate candidates by means of BRCAPRO, Myriad tables and IC software prediction models might exert on reduction of societal costs. Methods: 86 unrelated high risk breast/ovarian cancer families were selected for mutation screening; BRCA1/2 entire coding sequences and each intron/exon boundary were screened by direct sequencing (PTT limited to BRCA1 exon 11). The a priori probability of carrying a pathologic BRCA1/2 germline mutation was calculated by either BRCAPRO or IC software (country-customized versions of BRCAPRO), or by the Myriad prevalence mutation tables (2004). We classified our index cases as “carrier-positive” when their carrier probability exceeds 10%. According to recent literature, our analysis assumed a cost of $1,713 for genes sequencing of each proband. Results: We observed 19 pathogenic germline mutations with an overall detection rate of 22.1%. IC software and Myriad tables were more efficient in predicting mutated cases, showing higher sensitivity (95% and 84%, respectively) and a better negative predictive value (NPV, 96% and 91%, respectively) compared to BRCAPRO (sensitivity 74% and NPV 87%). Particularly, the IC software misclassified a pathogenic mutation carrier in only one case. The costs afforded for genetic testing on the whole sample was $147,318. The family selection assisted by the IC software, BRCAPRO, Myriad tables could result in a total cost of $104,493, $78,798 and $90,789, respectively. Even maintaining high accuracy in carrier status prediction, the country-customized version of BRCAPRO imparted more than 30% cost reduction. Conclusions: Considering a balance between economical advantages and the different performances in mutated status prediction, our analysis suggest that the country-customized versions of BRCAPRO and Myriad Tables allow efficient selection of candidates for BRCA1/2 mutation analysis and a significant impact on societal costs.

No significant financial relationships to disclose.
Quantitative real time-PCR of CD133 mRNA: A potential surrogate angiogenic marker of response for patients with metastatic sarcoma
Authors: Lin E. H. , Li Y. , Trent J. , Patel S. M. , Burgess M. A. , Steinert D. M. , Benjamin R. S. , Li D. , Chen L. L.
Published: March 2020

20034

Background: CD133 antigen is a specific surface marker for circulating endothelial progenitor cells (CEPs), pivotal in post-natal angiogenesis. We hypothesize that changes in levels of the CD133 mRNA expression and vascular endothelial growth factor (VEGF) may correlate with tumor response. Methods: After informed consent, we obtained 48 peripheral blood samples from patients with metastatic sarcoma including gastrointestinal stroma tumors (GIST). There were 16-paired samples before and after treatment including chemotherapy, or surgery, or imatinib. Of 24 patients with metastatic GIST enrolled, seven were paired samples. We measured CD133 mRNA levels by method (Lin E et al AACR 2003# 5392) and VEGF levels by ELISA (Genzyme, MA). The measurements were done in duplicates in two experiments. Results: The mean CD133 levels and VEGF levels before and after treatment was in Table 1 . The treatment resulted in significant reduction of CD133 mRNA expression (p = 0.035) as well as the level of VEGF (p = 0.014). Three patients experienced increase in CD133 expression had progressive disease. Among the paired GIST patients, there was a trend of increased CD133 mRNA expression levels in patients with progressive disease, death, or tumor recurrence. CD133 mRNA levels appeared elevated among the imatinib naïve patients and imatinib appeared to reset CD133 mRNA levels among the responding GIST patients to that of healthy volunteers. Conclusion: CD133 mRNA expression levels in sarcoma patients measured by real time-PCR assay appeared to correlate with tumor response. Unpublished independent work with NASBA assay platform in other solid tumors supported our findings ( www.primagen.com ). Further work is needed to reduce assay variability, and to determine the sensitivity and specificity of assay comparing to flow cytometry and to test assay’s applicability in the antiangiogenic therapy of cancer and the angiogenic therapy of cardiovascular diseases.

[Table: see text]

No significant financial relationships to disclose.
Spectrum of EGFR mutations associated with non-small cell lung cancer in an Asian Chinese population
Authors: Wong C. , Chan W. , Lam H. , Chan W. , Wang L. , Ma E.
Published: March 2020

20055

Background: Somatic mutations in tyrosine kinase (TK) domain of the EGFR gene, predicting for sensitivity to TK inhibition therapy, are over-represented in lung cancer with adenocarcinoma or bronchioloalveolar histology, non-smokers, female gender and East Asian ethnicity. Methods: We prospectively screened for EGFR mutations at exons 19–21 on micro-dissected specimen enriched for tumor cells by direct nucleotide sequencing in Hong Kong Chinese patients. Results: From May 2005 onwards, a total of 27 patients were analyzed. They comprised 11 males and 16 females with a median age of 67 years. Histological diagnoses were adenocarcinoma (n = 22), bronchioloalveolar carcinoma (n = 4) and squamous cell carcinoma (n = 1). Samples included primary tumor (n = 20) as well as metastatic lesions (n = 7). EGFR mutations were detected in 17 patients (63%), the most common being L858R at exon 21 (n = 7) followed by exon 19 deletions (del(746–750) = 3, del(747–751) = 1, del(747–753) = 3) and G719C at exon 18 (n = 1). Two patients showed novel EGFR mutations, namely 4-base pair insertion deletion at exon 19 leading to substitution of Glu746-Leu747 by Val746-Pro747 and three base pair deletion at exon 18 leading to replacement of Glu709-Thr710 by Asp. Furthermore, two patients showed double mutations, including novel S768I at exon 20 in combination with G719C, and novel K860I at exon 21 in combination with L858R. Finally, one patient showed homozygous del(747–753) as detected by sequencing in both primary lung tumor and brain secondary, which might represent loss of heterozygosity. Conclusions: Similar to other series, two hotspots i.e. exon 19 deletion and L858 account for the majority (82%) of detectable EGFR mutations in our patient population. For the rare and novel variants, it would be of interest to document the clinical responsiveness to TK inhibitors gefitinib and erlotinib, so that a more complete picture of cancer genotype phenotype correlation can be achieved.

No significant financial relationships to disclose.