Mutant KRAS Circulating Tumor DNA Is an Accurate Tool for Pancreatic Cancer Monitoring.

BACKGROUND: Many new pancreatic cancer treatment combinations have been discovered in recent years, yet the prognosis of pancreatic ductal adenocarcinoma (PDAC) remains grim. The advent of new treatments highlights the need for better monitoring tools for treatment response, to allow a timely switch between different therapeutic regimens. Circulating tumor DNA (ctDNA) is a tool for cancer detection and characterization with growing clinical use. However, currently, ctDNA is not used for monitoring treatment response. The high prevalence of KRAS hotspot mutations in PDAC suggests that mutant KRAS can be an efficient ctDNA marker for PDAC monitoring. SUBJECTS, MATERIALS, AND METHODS: Seventeen metastatic PDAC patients were recruited and serial plasma samples were collected. CtDNA was extracted from the plasma, and KRAS mutation analysis was performed using next-generation sequencing and correlated with serum CA19-9 levels, imaging, and survival. RESULTS: Plasma KRAS mutations were detected in 5/17 (29.4%) patients. KRAS ctDNA detection was associated with shorter survival (8 vs. 37.5 months). Our results show that, in ctDNA positive patients, ctDNA is at least comparable to CA19-9 as a marker for monitoring treatment response. Furthermore, the rate of ctDNA change was inversely correlated with survival. CONCLUSION: Our results confirm that mutant KRAS ctDNA detection in metastatic PDAC patients is a poor prognostic marker. Additionally, we were able to show that mutant KRAS ctDNA analysis can be used to monitor treatment response in PDAC patients and that ctDNA dynamics is associated with survival. We suggest that ctDNA analysis in metastatic PDAC patients is a readily available tool for disease monitoring. IMPLICATIONS FOR PRACTICE: Avoiding futile chemotherapy in metastatic pancreatic ductal adenocarcinoma (PDAC) patients by monitoring response to treatment is of utmost importance. A novel biomarker for monitoring treatment response in PDAC, using mutant KRAS circulating tumor DNA (ctDNA), is proposed. Results, although limited by small sample numbers, suggest that ctDNA can be an effective marker for disease monitoring and that ctDNA level over time is a better predictor of survival than the dynamics of the commonly used biomarker CA19-9. Therefore, ctDNA analysis can be a useful tool for monitoring PDAC treatment response. These results should be further validated in larger sample numbers.

Overall survival and clinical characteristics of BRCA mutation carriers with stage I/II pancreatic cancer.

BACKGROUND: BRCA1/BRCA2 germ line (GL) mutation carriers with pancreatic adenocarcinoma (PDAC) may have distinct outcomes. We recently described an apparent more favourable prognosis of surgically resected BRCA-associated PDAC patients in a single-arm, uncontrolled, retrospective study. However, the prognostic impact of GL BRCA1/2 mutations in surgically resected PDAC has not been compared with a matched control population. METHODS: A larger multi-centre, case-control retrospective analysis was performed. Cases were patients with surgically resected, BRCA1/2-associated PDAC from 2004 to 2013. Controls included surgically resected PDAC cases treated during the same time period that were either BRCA non-carriers, or had no family history of breast, ovarian or pancreatic cancers. Cases and controls were matched by: age at diagnosis (within ±5-year period) and institution. Demographics, clinical history, overall survival (OS) and disease-free survival (DFS) were abstracted from patient records. Statistical comparisons were assessed using χ2- and Fisher's exact test, and median DFS/OS using Kaplan-Meier method and log-rank testing. RESULTS: Twenty-five patients with BRCA1-(n=4) or BRCA2 (N=21)-associated resectable PDAC were identified. Mean age was 55.7 years (range, 34-78 years), 48% (n=12) were females and 76% (n=19) were Jewish. Cases were compared (1 : 2) with 49 resectable PDAC controls, and were balanced for age, ethnicity and other relevant clinical and pathological features. BRCA-associated PDAC patients received neoadjuvant, or adjuvant platinum-based treatment more frequently than controls (7 out of 8 vs 6 out of 14) and (7 out of 21 vs 3 out of 44), respectively. No significant difference in median OS (37.06 vs 38.77 months, P=0.838) and in DFS (14.3 vs 12.0 months, P=0.303) could be demonstrated between cases and controls. A trend to increased DFS was observed among BRCA-positive cases treated with neoadjuvant/adjuvant platinum-containing regimens (n=10) compared with similarly treated controls (n=7) (39.1 vs 12.4 months, P=0.255). CONCLUSIONS: In this retrospective analysis, the prognosis of surgically resectable BRCA-associated PDAC is no different than that of sporadic PDAC from the same institution. The role of platinum-based adjuvant therapy in this setting requires prospective investigation.

Modification of initial therapy in early and advanced Hodgkin lymphoma, based on interim PET/CT is beneficial: a prospective multicentre trial of 355 patients.

This multicentre study evaluated 5-year progression-free (PFS) and overall survival (OS) in early and advanced Hodgkin lymphoma (HL), where therapy was individualized based on initial prognostic factors and positron emission tomography-computed tomography performed after two cycles (PET-2). Between September 2006 and August 2013, 359 patients aged 18-60 years, were recruited in nine Israeli centres. Early-HL patients initially received ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) ×2. Depending on initial unfavourable prognostic features, PET-2-positive patients received additional ABVD followed by involved-site radiotherapy (ISRT). Patients with negative PET-2 and favourable disease received ISRT or ABVD ×2; those with unfavourable disease received ABVD ×2 with ISRT or, alternatively, ABVD ×4. Advanced-HL patients initially received ABVD ×2 or escalated BEACOPP (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, prednisone; EB) ×2 based on their international prognostic score (≤2 or ≥3). PET-2-negative patients further received ABVD ×4; PET-2-positive patients received EB ×4 and ISRT to residual masses. With a median follow-up of 55 (13-119) months, 5-year PFS was 91% and 69% for PET-2-negative and positive early-HL, respectively; 5-year OS was 100% and 95%, respectively. For advanced-HL, the PFS was 81% and 68%, respectively (P = 0·08); 5-year OS was 98% and 91%, respectively. PET-2 positivity is associated with inferior prognosis in early-HL, even with additional ABVD and ISRT. Advanced-HL patients benefit from therapy escalation following positive PET-2. EB can be safely de-escalated to ABVD in PET-2-negative patients.

Multisite Is Superior to Single-Site Intratumoral Chemotherapy to Retard the Outcomes of Pancreatic Ductal Adenocarcinoma in a Murine Model.

INTRODUCTION: Locally advanced unresectable pancreatic cancer (LAPC) has a dismal prognosis, with intratumoral therapies showing limited benefits. We assume that the dense stroma within these tumors hampers drug dispersion. AIM: This study explores the efficacy of multisite intratumoral injections in improving a drug's distribution while minimizing its side effects. METHODS AND RESULTS: In mice with orthotopic LAPC tumors, weekly intratumoral injections of oxaliplatin at four separate sites reduced the tumor growth by 46% compared with saline (p < 0.003). Oxaliplatin exhibited the greatest impact on the tumor microenvironment relative to gemcitabine, Abraxane, or their combination, with increased necrosis, apoptosis, fibroblasts, inflammation, and infiltrating lymphocytes (p < 0.008). When combined with intravenous FOLFIRINOX (FFX), multisite intratumoral oxaliplatin reduced the tumor weight by 35% compared with single-site injection (p = 0.007). No additional visible toxicity was observed even at a 10-fold occurrence of intratumoral treatment. This co-modality treatment significantly improved survival compared with other groups (p = 0.007). CONCLUSIONS: Multisite intratumoral therapy in tandem with systemic treatment holds promise for reducing the tumor size and enhancing the overall survival in LAPC.

A 10-year experience with treatment of high and standard risk Hodgkin disease: six cycles of tailored BEACOPP, with interim scintigraphy, are effective and female fertility is preserved.

Therapy of Hodgkin lymphoma (HL) is designed to prolong survival and minimize toxicity. A total of 124 patients with newly diagnosed HL and adverse prognostic factors were prospectively studied between July, 1999 and August, 2005. Patients with early unfavorable and advanced disease were eligible for the study. Patients were assigned to therapy based on international prognostic score (IPS). Those with IPS ≥ 3 received three cycles of escalated BEACOPP (EB). All others received two cycles of standard BEACOPP (SB). Subsequent therapy was prospectively assigned according to early interim GA(67) or positron emission tomography (PET)/computerized tomography (CT). Four cycles of EB or SB were administered following a positive or negative scan, respectively. Complete remission rate, 10-year progression free (PFS), and overall survival (OS) were 97, 87, and 88%, respectively, at a median follow-up of 89 months (5-144). PFS and OS were similar in both groups. Fertility status was assessed in 38 females aged <40 years; 94% of females younger than 40 years preserved their cyclic ovarian function. Nineteen conceived during follow-up for 30 pregnancies, delivering 24 babies. Deliveries were reported up to 7 years from diagnosis. Predictive value of negative interim Ga(67) or PET/CT was 87 and 93%, respectively. Six cycles of tailored BEACOPP, for patients with adverse prognostic factors, provide encouraging long-term PFS and OS, and fertility is preserved in most females.

A functional dynamic scoring model to elucidate the significance of post-induction interim fluorine-18-fluorodeoxyglucose positron emission tomography findings in patients with Hodgkin's lymphoma.

BACKGROUND: The findings of interim fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET/CT) predict progression-free survival of patients with Hodgkin's lymphoma. Historically, the assessment was based on a static all-or-none scoring system. However, the clinical significance of any positivity in interim FDG-PET/CT has not been defined. DESIGN AND METHODS: Ninety-six patients with Hodgkin's lymphoma who underwent interim FDG-PET/CT were evaluated using dynamic and visual scores, employing mediastinal or liver blood pool uptake as a comparator. FDG-PET/CT was prospectively defined as positive if any abnormal F(18)FDG uptake was present. In a retrospective analysis dynamic score 0 indicated resolution of all disease sites; score 1 defined a single residual focus; score 2 denoted a reduction in the number of foci; score 3 defined a reduction in intensity with no reduction in number; and score 4 indicated no change in the number and intensity of foci or appearance of new foci. RESULTS: The dynamic visual score review reduced the number of positive interim studies from 24 to 6 if a score of 2 or less was considered negative, with significantly better specificity (96%) as compared to static visual scores (78%-86%). The 5-year progression-free survival and overall survival rates in patients who had a negative dynamic score were 92% and 97%, respectively; the corresponding figures for patients with positive results were 50% and 67%. CONCLUSIONS: A dynamic visual score may be a better indicator for tailoring therapy than static visual scoring.

Curcumin and gemcitabine in patients with advanced pancreatic cancer.

Curcumin has a potent antiproliferative activity and can also potentiate the antitumor effect of gemcitabine. This study was undertaken to evaluate the activity and feasibility of gemcitabine in combination with curcumin in patients with advanced pancreatic cancer. Seventeen patients were enrolled in the study and received 8,000 mg of curcumin by mouth daily, concurrently with gemcitabine 1,000 mg/m(2) IV weekly × 3 of 4 wk; 5 patients (29%) discontinued curcumin after a few days to 2 wk due to intractable abdominal fullness or pain, and the dose of curcumin was reduced to 4,000 mg/day because of abdominal complaints in 2 other patients. One of 11 evaluable patients (9%) had partial response, 4 (36%) had stable disease, and 6 (55%) had tumor progression. Time to tumor progression was 1-12 mo (median 2½), and overall survival was 1-24 mo (median 5). Low compliance for curcumin at a dose of 8,000 mg/day, when taken together with systemic gemcitabine, may prevent the use of high doses of oral curcumin needed to achieve systemic effect. Further studies should be conducted to evaluate the ability of other formulations of curcumin to enhance the effect of chemotherapy in cancer patients.

The Older Adults With Rectal Cancer-Does Age Matter?: A Single-center Experience.

OBJECTIVES: Oncological treatments of older patients have many unresolved questions mainly because of the fact that these patients were not eligible to be included in most clinical trials. The aim of this study was to evaluate the treatment approach to localized rectal cancer in the older population, including complication rates and overall survival in patients treated with curative intent. MATERIALS AND METHODS: A retrospective review of patients older than 80 years old (group A) who were treated for clinical stages II to III rectal cancer. The data collection included demographics, comorbidities, treatment protocols, adverse events, time of death, and a comparison with a group of patients aged 65 to 75 years (group B). RESULTS: A total of 88 patients were included in the analysis (group A, 35; group B, 53). The groups were balanced with regards to sex, comorbidities, pretreatment albumin, and hemoglobin levels (for all categories P>0.05). More patients in group A (25%) received preoperative treatment as in-patients (P=0.022) and were treated with radiation only (P<0.0001) as the initial treatment approach. In group A, in 82% of patients the initial chemotherapy dose was reduced to 75% or less of the calculated dose compared with 7% in group B (P<0.001). Discontinuation of chemotherapy was needed in 55% in group A and 31% in group B (P=0.07). Median overall survival was 33 months in group A and 55 months in group B (P=0.06), 5-year overall survival was 27% and 60%, respectively (P=0.004). CONCLUSIONS: The age has a significant implication on preoperative treatment, chemotherapy dose, hospitalization rates, and survival.

Primary breast lymphoma: patient profile, outcome and prognostic factors. A multicentre Rare Cancer Network study.

BACKGROUND: To asses the clinical profile, treatment outcome and prognostic factors in primary breast lymphoma (PBL). METHODS: Between 1970 and 2000, 84 consecutive patients with PBL were treated in 20 institutions of the Rare Cancer Network. Forty-six patients had Ann Arbor stage IE, 33 stage IIE, 1 stage IIIE, 2 stage IVE and 2 an unknown stage. Twenty-one underwent a mastectomy, 39 conservative surgery and 23 biopsy; 51 received radiotherapy (RT) with (n = 37) or without (n = 14) chemotherapy. Median RT dose was 40 Gy (range 12-55 Gy). RESULTS: Ten (12%) patients progressed locally and 43 (55%) had a systemic relapse. Central nervous system (CNS) was the site of relapse in 12 (14%) cases. The 5-yr overall survival, lymphoma-specific survival, disease-free survival and local control rates were 53%, 59%, 41% and 87% respectively. In the univariate analyses, favorable prognostic factors were early stage, conservative surgery, RT administration and combined modality treatment. Multivariate analysis showed that early stage and the use of RT were favorable prognostic factors. CONCLUSION: The outcome of PBL is fair. Local control is excellent with RT or combined modality treatment but systemic relapses, including that in the CNS, occurs frequently.

Rucaparib Monotherapy in Patients With Pancreatic Cancer and a Known Deleterious BRCA Mutation.

PURPOSE: Pancreatic cancer has a poor prognosis and limited treatment options. Approximately 9% of pancreatic cancers harbor a germline or somatic BRCA1 or BRCA2 (BRCA1/2) mutation. Because poly (ADP-ribose) polymerase inhibitors have significant activity in BRCA1/2-mutant ovarian and breast cancers, RUCAPANC investigated the efficacy and safety of rucaparib in BRCA1/2-mutant pancreatic cancer. PATIENTS AND METHODS: RUCAPANC enrolled patients with measurable locally advanced/metastatic pancreatic cancer who had received one to two prior chemotherapy regimens. Patients received oral rucaparib (600 mg twice daily) until disease progression. The primary end point was objective response rate. RESULTS: Nineteen patients were enrolled. Sixteen of 19 BRCA1/2 mutations were germ-line; three were somatic. Patients had received a median of two prior chemotherapy regimens. Four patients achieved a response; two partial responses and one complete response (CR) were confirmed (objective response rate, 15.8%; 3 of 19), with an additional CR unconfirmed. The disease control rate (CR, partial response, or stable disease for ≥ 12 weeks) was 31.6% (6 of 19) in all patients and 44.4% (4 of 9) in those who had received one prior chemotherapy regimen. As prespecified in the protocol, enrollment was stopped because of an insufficient response rate among the first 15 patients. Treatment-emergent adverse events included nausea (63.2%) and anemia (47.4%). Grade ≥ 3 adverse events included anemia (31.6%), fatigue (15.8%), and ascites (15.8%). Secondary resistance mutations were detected in circulating free tumor DNA in two patients with a germline BRCA2 mutation. These mutations are predicted to lead to the reversion of a somatic-not germline-mutation. CONCLUSION: Rucaparib provided clinical benefit to patients with advanced pancreatic cancer and a BRCA1/2 mutation, and demonstrated an acceptable safety profile. Additional trials of rucaparib in this population are warranted.

Primary spinal epidural lymphoma: patients' profile, outcome, and prognostic factors: a multicenter Rare Cancer Network study.

PURPOSE: To assess the clinical profile, treatment outcome, and prognostic factors in primary spinal epidural lymphoma (PSEL). METHODS AND MATERIALS: Between 1982 and 2002, 52 consecutive patients with PSEL were treated in nine institutions of the Rare Cancer Network. Forty-eight patients had an Ann Arbor stage IE and four had a stage IIE. Forty-eight patients underwent decompressive laminectomy, all received radiotherapy (RT) with (n = 32) or without chemotherapy (n = 20). Median RT dose was 36 Gy (range, 6-50 Gy). RESULTS: Six (11%) patients progressed locally and 22 (42%) had a systemic relapse. At last follow-up, 28 patients were alive and 24 had died. The 5-year overall survival, disease-free survival, and local control were 69%, 57%, and 88%, respectively. In univariate analyses, favorable prognostic factors were younger age and complete neurologic response. Multivariate analysis showed that combined modality treatment, RT volume, total dose more than 36 Gy, tumor resection, and complete neurologic response were favorable prognostic factors. CONCLUSIONS: Primary spinal epidural lymphoma has distinct clinical features and outcome, with a relatively good prognosis. After therapy, local control is excellent and systemic relapse occurs in less than half the cases. Combined modality treatment appears to be superior to RT alone.

Metabolic assessment of Merkel cell carcinoma: the role of 18F-FDG PET/CT.

OBJECTIVES: Merkel cell carcinoma (MCC) is a rare aggressive skin tumor associated with a high mortality rate. The present study evaluated the role of fluorine-18 fluorodeoxyglucose (F-FDG) PET/computed tomography (CT) in subsequent management of patients with MCC. METHODS: A total of 101 consecutive F-FDG PET/CT studies of 46 patients with MCC (28 men, 68±15.4 years) were retrospectively evaluated and the role in clinical care was documented. RESULTS: There were 40 positive studies (40%) in 28 patients (61%); of these, 33 studies (33%) in 27 patients (59%) showed metastatic disease. Fifty-two PET/CT studies (51%) in 23/46 (50%) patients were negative. Fifty-three studies (52%) were performed for staging or restaging in 41 patients, 29 scans (29%) were performed for routine follow-up in 10 patients, nine studies were carried out for suspected recurrent disease in eight patients, and 10 studies were carried out for assessment of response to therapy in seven patients. On the basis of PET/CT results, there was a change in disease stage in 12 studies in 12 patients (26%) and further change in the management of seven patients (15%). Overall, 2/29 routine follow-up studies were positive with further impact on management in one patient. CONCLUSION: F-FDG PET-CT altered the stage of one of four patients and changed the management of one of seven MCC patients. In the majority of patients, a negative F-FDG PET-CT study excluded active MCC with a high degree of confidence. PET-CT contributed toward patient management when performed for staging and restaging, monitoring response to treatment, and suspected recurrent disease, but not in the routine follow-up of asymptomatic patients with MCC.

The Medical Use of Wheatgrass: Review of the Gap Between Basic and Clinical Applications.

A wide range of health benefits have been attributed to wheatgrass, the young grass of the common wheat plant Triticum aestivum. Its components include chlorophyll, flavonoids, and vitamins C and E. Forms of wheatgrass include fresh juice, frozen juice, tablets, and powders, with compositions varying according to their production processes, as well as to the growing conditions of the wheatgrass. Laboratory in vitro studies, mostly using the fermented wheat germ extract, have demonstrated anti-cancer potential and have identified apoptosis as a possible mechanism. In animal experiments, wheatgrass demonstrated benefits in cancer prevention and as an adjunct to cancer treatment, as well as benefits to immunological activity and oxidative stress. Clinical trials show that wheatgrass may induce synergistic benefits to chemotherapy and may attenuate chemotherapy-related side effects, as well as benefit rheumatoid arthritis, ulcerative colitis, hematological diseases, diabetes, obesity, and oxidative stress. However, all the trials were small and a number of methodological problems arose. No adverse events of wheatgrass have been reported, although some forms pose problems of tolerability. The popularity of wheatgrass continues to grow. Nevertheless, the advantages seen in the clinical trials need to be proved in larger studies before clinical recommendations for the public can be given.

Molecular Profiling-Selected Therapy for Treatment of Advanced Pancreaticobiliary Cancer: A Retrospective Multicenter Study.

This multicenter cohort study assessed the impact of molecular profiling (MP) on advanced pancreaticobiliary cancer (PBC). The study included 30 patients treated with MP-guided therapy after failing ≥ 1 therapy for advanced PBC. Treatment was considered as having benefit for the patient if the ratio between the longest progression-free survival (PFS) on MP-guided therapy and the PFS on the last therapy before MP was ≥ 1.3. The null hypothesis was that ≤ 15% of patients gain such benefit. Overall, ≥ 1 actionable (i.e., predictive of response to specific therapies) biomarker was identified/patient. Immunohistochemistry (the most commonly used method for guiding treatment decisions) identified 1-6 (median: 4) actionable biomarkers per patient. After MP, patients received 1-4 (median: 1) regimens/patient (most commonly, FOLFIRI/XELIRI). In a decision-impact analysis, of the 27 patients for whom treatment decisions before MP were available, 74.1% experienced a treatment decision change in the first line after MP. Twenty-four patients were evaluable for clinical outcome analysis; in 37.5%, the PFS ratio was ≥ 1.3. In one-sided exact binomial test versus the null hypothesis, P = 0.0015; therefore, the null hypothesis was rejected. In conclusion, our analysis demonstrated the feasibility, clinical decision impact, and potential clinical benefits of MP-guided therapy in advanced PBC.

Is 18F-FDG PET/CT useful for imaging and management of patients with suspected occult recurrence of cancer?

UNLABELLED: Rising serum tumor markers may be associated with negative imaging in the presence of cancer. CT and (18)F-FDG PET may yield incongruent results in the assessment of tumor recurrence. The present study evaluates the incremental role of (18)F-FDG PET/CT for the diagnosis and management of cancer patients with increasing levels of tumor markers as the sole indicator of potential recurrence after initial successful treatment. METHODS: Thirty-six cancer patients with increasing levels of tumor markers during follow-up and negative CT underwent (18)F-FDG PET/CT, which showed 111 sites of increased tracer uptake. PET/CT was compared with PET results on a site-based analysis for characterization of (18)F-FDG foci and on a patient-based analysis for diagnosis of recurrence. The clinical impact of PET/CT on further patient management was evaluated. RESULTS: Thirty patients (83%) had recurrence in 85 malignant sites (77%). For the site-based analysis, PET had a sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of 96%, 50%, 85%, 85%, and 82%, respectively, as compared with the performance indices of PET/CT of 100%, 89%, 97%, 97%, and 100%, respectively. There was a statistically significant difference between the specificity (P < 0.05) and accuracy (P < 0.001) of PET and PET/CT for precise characterization of suspected lesions. For the patient-based analysis, PET had a sensitivity, specificity, and accuracy of 93%, 50%, and 86%, respectively, as compared with PET/CT with values of 93%, 67%, and 89%, respectively (P = not significant). PET/CT was the single modality that directed further management and treatment planning in 12 patients (33%). CONCLUSION: The results of this study indicate that PET/CT may improve the accuracy of occult cancer detection and further lead to management changes in patients with increasing levels of tumor markers as the sole suspicion of recurrent malignancy.

Bone lymphoma: 67Ga scintigraphy and CT for prediction of outcome after treatment.

UNLABELLED: The purpose of the present study was to evaluate the role of 67Ga scintigraphy and CT in treatment monitoring of bone lymphoma. METHODS: Forty-four lymphoma patients with 91 sites of bone involvement were evaluated. Eight patients had Hodgkin's disease, and 36 patients had non-Hodgkin's lymphoma. Thirteen patients had primary lymphoma of the bone, and 31 patients had secondary lymphoma of the skeleton. 67Ga and CT studies were performed at baseline, during and at the end of treatment, and during follow-up. Positive 67Ga studies showed abnormal uptake in sites of lymphomatous involvement. Positive CT studies showed lesions with patterns of osteolysis, patterns of osteosclerosis, or a mixed pattern. A negative 67Ga or CT study showed disappearance of all lymphoma-related abnormalities. The sensitivity and specificity of 67Ga scintigraphy at presentation were calculated. Patterns of bone lymphoma on CT and their treatment-related changes were analyzed and recorded. Freedom-from-progression (FFP) curves were used to determine the prognostic value of positive and negative 67Ga and CT findings for predicting outcome after treatment. RESULTS: The sensitivity of 67Ga for diagnosis of bone lymphoma was 93%, and the specificity was 91%. A CT pattern of osteolysis was seen in 70% of skeletal disease sites at diagnosis and in 21% during follow-up. Osteosclerosis was present in 23% of sites at diagnosis and in 38% during follow-up. 67Ga findings became negative in 25% of patients during treatment, whereas only 1 patient showed negative CT findings. Forty-two percent of patients had negative 67Ga findings at the end of treatment, compared with 18% who had negative CT findings. Sixty-one percent of patients had negative 67Ga findings during follow-up, compared with 21% who had negative CT findings. A statistically significant difference in FFP was found between patients with positive and negative 67Ga findings at all evaluated time points. No statistically significant difference in FFP was found at any time point between patients with positive and negative CT findings. CONCLUSION: 67Ga scintigraphy has a high sensitivity and specificity for diagnosis of bone lymphoma. Bone lymphoma may show osteosclerotic and osteolytic CT patterns at diagnosis, during treatment, and after treatment. In most patients, CT studies do not become negative even 1 y after treatment. 67Ga scintigraphy, however, may be used as a predictor of long-term outcome in patients with lymphoma of the skeleton.

Excellent long-term survival in patients with early-stage primary bone lymphoma treated with doxorubicin-based chemotherapy and local radiotherapy.

Primary bone lymphoma accounts for less than 5% of primary extranodal presentations, and the majority are of the diffuse, large cell, B-cell type. The study presents the authors' 21 years of experience (1979-2000) in ten patients with early stage (IE-IIE) primary bone lymphoma. All patients were treated with doxorubicin-based chemotherapy. Seven received consolidation radiotherapy to an area encompassing the primary tumor with generous margins, including the adjacent soft tissues, and in two stage IIE patients also to the regional lymph nodes. Mean total dose was 3989 cGy. Nine patients are alive with no evidence of recurrent disease. There are no severe late side effects, and only one patient died due to therapy-resistant small cell lung cancer (second primary), while in complete remission from his primary lymphoma. Albeit retrospective in nature with a small patient accrual, this study demonstrates that primary bone lymphoma is a curable disease following aggressive doxorubicin-based chemotherapy. The exact rule of radiation therapy is yet to be determined.

Natural products as potential cancer therapy enhancers: A preclinical update.

Cancer is a multifactorial disease that arises as a consequence of alterations in many physiological processes. Recently, hallmarks of cancer were suggested that include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis, along with two emerging hallmarks including reprogramming energy metabolism and escaping immune destruction. Treating multifactorial diseases, such as cancer with agents targeting a single target, might provide partial treatment and, in many cases, disappointing cure rates. Epidemiological studies have consistently shown that the regular consumption of fruits and vegetables is strongly associated with a reduced risk of developing chronic diseases, such as cardiovascular diseases and cancer. Since ancient times, plants, herbs, and other natural products have been used as healing agents. Moreover, the majority of the medicinal substances available today have their origin in natural compounds. Traditionally, pharmaceuticals are used to cure diseases, and nutrition and herbs are used to prevent disease and to provide an optimal balance of macro- and micro-nutrients needed for good health. We explored the combination of natural products, dietary nutrition, and cancer chemotherapeutics for improving the efficacy of cancer chemotherapeutics and negating side effects.

Tumor aggressiveness and patient outcome in cancer of the pancreas assessed by dynamic 18F-FDG PET/CT.

UNLABELLED: This study aimed to assess the role of a quantitative dynamic PET model in pancreatic cancer as a potential index of tumor aggressiveness and predictor of survival. METHODS: Seventy-one patients with (18)F-FDG-avid adenocarcinoma of the pancreas before treatment were recruited, including 27 with localized tumors (11 underwent pancreatectomy, and 16 had localized nonresectable tumors) and 44 with metastatic disease. Dynamic (18)F-FDG PET images were acquired over a 60-min period, followed by a whole-body PET/CT study. Quantitative data measurements were based on a 2-compartment model, and the following variables were calculated: VB (fractional blood volume in target area), K(1) and k(2) (kinetic membrane transport parameters), k(3) and k(4) (intracellular (18)F-FDG phosphorylation and dephosphorylation parameters, respectively), and (18)F-FDG INF (global (18)F-FDG influx). RESULTS: The single significant variable for overall survival (OS) in patients with localized disease was (18)F-FDG INF. Patients with a high (18)F-FDG INF (>0.033 min(-1)) had a median OS of 6 and 5 mo for nonresectable and resected tumors, respectively, versus 15 and 19 mo for a low (18)F-FDG INF in nonresectable and resected tumors, respectively (P < 0.04). In metastatic disease, multivariate analysis found VB, K(1), and k(3) to be significant variables for OS (P < 0.043, <0.031, and <0.009, respectively). Prognostic factors for OS in the entire group of patients that were significant at multivariate analysis were stage of disease, VB, K(1), and (18)F-FDG INF (P < 0.00035, <0.03, <0.024, and <0.008, respectively). Median OS for all patients with a high (18)F-FDG INF, low VB, and high K(1) was 3 mo, as opposed to 14 mo in patients with a low (18)F-FDG INF, high VB, and low K(1) (P < 0.021), irrespective of stage and resectability. CONCLUSION: Quantitative (18)F-FDG kinetic parameters measured by dynamic PET in newly diagnosed pancreatic cancer correlated with the aggressiveness of disease. The (18)F-FDG INF was the single most significant variable for OS in patients with localized disease, whether resectable or not.

Accuracy and Quality Assessment of EUS-FNA: A Single-Center Large Cohort of Biopsies.

Introduction. Thorough quality control (QC) study with systemic monitoring and evaluation is crucial to optimizing the effectiveness of EUS-FNA. Methods. Retrospective analysis was composed of investigating consecutive patient files that underwent EUS-FNA. QC specifically focused on diagnostic accuracy, impacts on preexisting diagnoses, and case management. Results. 268 patient files were evaluated. EUS-FNA cytology helped establish accurate diagnoses in 92.54% (248/268) of patients. Sensitivity, specificity, PPV, NPV, and accuracy were 83%, 100%, 100%, 91.6%, and 94%, respectively. The most common biopsy site was the pancreas (68%). The most accurate location for EUS-FNA was the esophagus, 13/13 (100%), followed by the pancreas (89.6%). EUS-FNA was least informative for abdominal lymph nodes (70.5%). After FNA and followup, eight false negatives for tumors were found (3%), while 7.5% of samples still lacked a definitive diagnosis. Discussion. QC suggests that the diagnostic accuracy of EUS-FNA might be improved further by (1) taking more FNA passes from suspected lesions, (2) optimizing needle selection (3) having an experienced echo-endoscopist available during the learning curve, and (4) having a cytologist present during the procedure. QC also identified remediable reporting errors. In conclusion, QC study is valuable in identifying weaknesses and thereby augmenting the effectiveness of EUS-FNA.