Robert Zaiden

Involved-node proton therapy in combined modality therapy for Hodgkin lymphoma: results of a phase 2 study.

PURPOSE This study describes the early clinical outcomes of a prospective phase 2 study of consolidative involved-node proton therapy (INPT) as a component of combined-mode therapy in patients with stages I to III Hodgkin lymphoma (HL) with mediastinal involvement. METHODS AND MATERIALS Between September 2009 and June 2013, 15 patients with newly diagnosed HL received INPT after completing chemotherapy in an institutional review board-approved protocol comparing the dosimetric impact of PT with those of three-dimensional conformal radiation therapy (3DCRT) and intensity modulated RT. Based on (18)F-Fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) response, 5 children received 15 to 25.5 cobalt Gy equivalent (CGE) of INPT after receiving 4 cycles of Adriamycin, Bleomycin, Vincristine, Etoposide, Prednisone, Cyclophosphamide or Vincristine, adriamycin, methotrexate, Prednisone chemotherapy, and 10 adults received 30.6 to 39.6 CGE of INPT after 3 to 6 cycles of Adriamycin, Bleomycine, Vinblastine, Dacarbazine. Patients were routinely evaluated for toxicity during and after treatment, using Common Terminology Criteria for Adverse Events, version 3.0, and for relapse by physical examination and routine imaging. Relapse-free survival (RFS) and event-free survival (EFS) rates were calculated using the Kaplan-Meier method from the time of diagnosis. RESULTS The median follow-up was 37 months (range, 26-55). Two events occurred during follow-up: 1 relapse (inside and outside the targeted field) and 1 transformation into a primary mediastinal large B cell lymphoma. The 3-year RFS rate was 93%, and the 3-year EFS rate was 87%. No acute or late grade 3 nonhematologic toxicities were observed. CONCLUSIONS Although decades of follow-up will be needed to realize the likely benefit of PT in reducing the risk of radiation-induced late effects, PT following chemotherapy in patients with HL is well-tolerated, and disease outcomes were similar to those of conventional photon therapy.

Proton therapy with concomitant capecitabine for pancreatic and ampullary cancers is associated with a low incidence of gastrointestinal toxicity

Abstract Background. To review treatment toxicity for patients with pancreatic and ampullary cancer treated with proton therapy at our institution. Material and methods. From March 2009 through April 2012, 22 patients were treated with proton therapy and concomitant capecitabine (1000 mg PO twice daily) for resected (n = 5); marginally resectable (n = 5); and unresectable/inoperable (n = 12) biopsy-proven pancreatic and ampullary adenocarcinoma. Two patients with unresectable disease were excluded from the analysis for reasons unrelated to treatment. Proton doses ranged from 50.40 cobalt gray equivalent (CGE) to 59.40 CGE. Results. Median follow-up for all patients was 11 (range 5–36) months. No patient demonstrated any grade 3 toxicity during treatment or during the follow-up period. Grade 2 gastrointestinal toxicities occurred in three patients, consisting of vomiting (n = 3); and diarrhea (n = 2). Median weight loss during treatment was 1.3 kg (1.75% of body weight). Chemotherapy was well-tolerated with a median 99% of the prescribed doses delivered. Percentage weight loss was reduced (p = 0.0390) and grade 2 gastrointestinal toxicity was eliminated (p = 0.0009) in patients treated with plans that avoided anterior and left lateral fields which were associated with reduced small bowel and gastric exposure. Discussion. Proton therapy may allow for significant sparing of the small bowel and stomach and is associated with a low rate of gastrointestinal toxicity. Although long-term follow-up will be needed to assess efficacy, we believe that the favorable toxicity profile associated with proton therapy may allow for radiotherapy dose escalation, chemotherapy intensification, and possibly increased acceptance of preoperative radiotherapy for patients with resectable or marginally resectable disease.

Blood Culture Isolates in Hemodialysis Vascular Catheter-Related Bacteremia

Hemodialysis requires reliable and recurrent access to the central circulation and arteriovenous fistulas or grafts are the preferred modes of vascular access. However, in many patients the use of external tunneled vascular catheters may be necessary. The major complication of tunneled catheters is infection. Understanding local epidemiologic patterns of dialysis catheter-related bacteremia may help in the management of these patients. To address this issue, we reviewed the 5-year microbiologic culture results from all bacteremic hemodialysis patients with tunneled catheters at our institution. During this period, there were 203 organisms isolated from 153 positive blood cultures. Gram-positive, Gram-negative, and fungal species represented 55.7%, 43.3%, and 1% of isolates, respectively. Positive blood cultures classified according to the presence of a single Gram-positive or single Gram-negative organism, single fungus, or polymicrobial organisms, accounted for 41.8%, 29.4%, 0.6% and 28.1% of infectious events. From 2000–2004, there was a numerical trend toward a decrease in Gram-positive infection (64.3% versus 34.8% respectively, P = 0.12) and a numerical trend toward an increase in Gram-negative and polymicrobial bacteremias (17.9 versus 21.7, P = 0.07 and 17.9 versus 43.5, P = 0.09, respectively). These data indicate that bacteremic events in hemodialysis patients with vascular catheters are commonly due to a single Gram-positive organism, but the incidence of Gram-negative and polymicrobial bacteremia may be increasing. If confirmed in a prospective trial, adjustment of empiric antibiotic regimens for suspected catheter-associated bacteremia may be indicated.

Proton Therapy and Concomitant Capecitabine for Non-Metastatic Unresectable Pancreatic Adenocarcinoma

Abstract Purpose: To review early outcomes for patients enrolled on our institutions protocol (PC01) for patients with unresectable pancreatic cancer, and to test whether the serious adverse event rate could be reduced from 15% (expected) to <5%. Patients and Methods: Twelve patients were enrolled, but only 11 patients are reported in this analysis. Pathology on all patients was reviewed at University of Florida Health Medical Center in Jacksonville to confirm the diagnosis of pancreatic adenocarcinoma. Unresectability was defined by radiographic evidence of encasement of the celiac axis and/or superior mesenteric artery or by occlusion of the superior mesenteric vein, portal vein, or both confluences. Patients received proton therapy to a planning target volume dose of 59.4 Gy (relative biological effective) at 1.8 Gy (relative biological effective) per fraction over 7 weeks with concomitant oral capecitabine (1000 mg orally twice-daily, 5 days/week on radiation treatment days only). Only gross disease ...

Hepatitis C infection and the risk of bacteremia in hemodialysis patients with tunneled vascular access catheters.

Background: The major complication of tunneled vascular catheters in dialysis patients is infection. In preliminary work, an association was noted between hepatitis C virus (HCV) infection and bacteremia in these patients. On this basis, we theorized that HCV infection may be associated with bacteremia in dialysis patients with tunneled catheters. Methods: We conducted a two-phase clinical study to define the association between HCV infection and bacteremia in hemodialysis patients with catheters. Phase 1 was a cross-sectional study designed to assess the association between HCV serologic status and bacteremia. Phase 2 was a prospective study that examined the relationship between HCV viral load and bacteremia. Results: In Phase 1, HCV (+) patients had a significantly greater prevalence of bacteremia than HCV (−) patients (61 vs 7.7% respectively, P < 0.05). In Phase 2, the presence of detectable virus was associated with a numerical trend toward an increase in the incidence of bacteremia (40 vs 0% for patients with and without detectable virus, respectively, P = 0.09). Conclusion: These studies suggest that HCV infection may be associated with the development of bacteremia in hemodialysis patients with tunneled catheters.

Proton therapy may allow for comprehensive elective nodal coverage for patients receiving neoadjuvant radiotherapy for localized pancreatic head cancers.

BACKGROUND Neoadjuvant radiotherapy has the potential to improve local disease control for patients with localized pancreatic cancers. Concern about an increased risk of surgical complications due to small bowel and gastric exposure, however, has limited enthusiasm for this approach. Dosimetric studies have demonstrated the potential for proton therapy to reduce intestinal exposure compared with X-ray-based therapy. We sought to determine if neoadjuvant proton therapy allowed for field expansions to cover high-risk nodal stations in addition to the primary tumor. METHODS Twelve consecutive patients with nonmetastatic cancers of the pancreatic head underwent proton-based planning for neoadjuvant radiotherapy. Gross tumor volume was contoured using diagnostic computed tomography (CT) scans with oral and intravenous contrast. Four-dimensional planning scans were utilized to define an internal clinical target volume (ICTV). Five-mm planning target volume (PTV) expansions on the ICTV were generated to establish an initial PTV (PTV1). A second PTV was created using the initial PTV but was expanded to include the high-risk nodal targets as defined by the RTOG contouring atlas (PTV2). Optimized proton plans were generated for both PTVs for each patient. All PTVs received a dose of 50.4 cobalt gray equivalent (CGE). Normal-tissue exposures to the small bowel space, stomach, right kidney, left kidney and liver were recorded. Point spinal cord dose was limited to 45 CGE. RESULTS Median PTV1 volume was 308.75 cm(3) (range, 133.33-495.61 cm(3)). Median PTV2 volume was 541.75 cm(3) (range, 399.44-691.14 cm(3)). In spite of the substantial enlargement of the PTV when high-risk lymph nodes were included in the treatment volume, normal-tissue exposures (stomach, bowel space, liver, and kidneys) were only minimally increased relative to the exposures seen when only the gross tumor target was treated. CONCLUSIONS Proton therapy appears to allow for field expansions to cover high-risk lymph nodes without significantly increasing critical normal-tissue exposure in the neoadjuvant setting.

Feasibility of pancreatectomy following high-dose proton therapy for unresectable pancreatic cancer

AIM To review surgical outcomes for patients undergoing pancreatectomy after proton therapy with concomitant capecitabine for initially unresectable pancreatic adenocarcinoma. METHODS From April 2010 to September 2013, 15 patients with initially unresectable pancreatic cancer were treated with proton therapy with concomitant capecitabine at 1000 mg orally twice daily. All patients received 59.40 Gy (RBE) to the gross disease and 1 patient received 50.40 Gy (RBE) to high-risk nodal targets. There were no treatment interruptions and no chemotherapy dose reductions. Six patients achieved a radiographic response sufficient to justify surgical exploration, of whom 1 was identified as having intraperitoneal dissemination at the time of surgery and the planned pancreatectomy was aborted. Five patients underwent resection. Procedures included: Laparoscopic standard pancreaticoduodenectomy (n = 3), open pyloris-sparing pancreaticoduodenectomy (n = 1), and open distal pancreatectomy with irreversible electroporation (IRE) of a pancreatic head mass (n = 1). RESULTS The median patient age was 60 years (range, 51-67). The median duration of surgery was 419 min (range, 290-484), with a median estimated blood loss of 850 cm3 (range, 300-2000), median ICU stay of 1 d (range, 0-2), and median hospital stay of 10 d (range, 5-14). Three patients were re-admitted to a hospital within 30 d after discharge for wound infection (n = 1), delayed gastric emptying (n = 1), and ischemic gastritis (n = 1). Two patients underwent R0 resections and demonstrated minimal residual disease in the final pathology specimen. One patient, after negative pancreatic head biopsies, underwent IRE followed by distal pancreatectomy with no tumor seen in the specimen. Two patients underwent R2 resections. Only 1 patient demonstrated ultimate local progression at the primary site. Median survival for the 5 resected patients was 24 mo (range, 10-30). CONCLUSION Pancreatic resection for patients with initially unresectable cancers is feasible after high-dose [59.4 Gy (RBE)] proton radiotherapy with a high rate of local control, acceptable surgical morbidity, and a median survival of 24 mo.

Abstract P4-11-35: The association of serum albumin and glycated hemoglobin with all cause mortality in patients with breast cancer

Background: There has been increasing data within the oncology literature to support an inverse relationship between serum albumin levels and survival with breast cancer. Various studies have also indicated that diabetes is associated with a higher mortality in patients with breast cancer. Given the need to develop objective ways to identify patients with a poorer than expected outcome, the aim of this study is to determine whether serum albumin and glycated hemoglobin at diagnosis bears any relationship with all cause mortality in patients with all stages of breast cancer. Methods: We performed a retrospective study of patients diagnosed with breast cancer of all stages at University of Florida Health Center, Jacksonville between August 2007 and October 2013. The data for this study was obtained from a combination of the hospital tumor registry and the electronic medical record. We collected data including age, sex, stage of cancer, histological type, tumour size and grade, lymph node status, estrogen (ER), progesterone (PR) and HER2/Neu receptor status. We collected baseline serum albumin levels and glycated hemoglobin (HbA1C) values recorded within 3 months of diagnosis of breast cancer. Wilcoxon’s rank sum test was used to test whether cancer stage differed between survival outcomes. Spearman correlation was used to assess the relationship between cancer stage and serum albumin and HbA1C at time of diagnosis. Logistic regression was used to model the impact of HbA1c, serum albumin and age at time of diagnosis on the probability of survival. Results: The number of patients with breast cancer included in our study was 294. Of these patients, 219 patients had serum albumin values available at diagnosis and 69 patients had glycated hemoglobin values at diagnosis. The correlation between serum albumin and stage is statistically significant (P The negative correlation means that higher levels of serum albumin are associated with lower stages. Serum albumin at diagnosis had a significant effect on the probability of survival (p=0.0005). For every unit increase in serum albumin, the odds of survival increase (OR=4.938, 95% CI: 2.023, 12.050). Alternatively, for each unit decrease the odds of dying increase by about five fold. Hypoalbuminemia has a significant effect on survival (p=0.0020). When serum albumin is >3.5, the odds of death decrease (OR=0.176 95% CI: 0.058, 0.528). Neither HbA1c nor age had a significant effect on survival (P=0.7635, 0.0858 respectively). Conclusion: In the present study, a low serum albumin level at the time of diagnosis, either as a continuous or categoric variable, was significantly associated with poorer survival in patients with breast cancer. Furthermore, a lower serum albumin is associated with a higher stage of breast cancer. In contrast, glycated hemoglobin (HbA1C) at the time of diagnosis did not have a significant effect on survival. Citation Format: Vinay N Minocha, Kavita Pal, Robert Zaiden. The association of serum albumin and glycated hemoglobin with all cause mortality in patients with breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-11-35.

Effect of protons on bone marrow and small-bowel exposure for patients receiving neoadjuvant radiotherapy for resectable rectal cancer.

669 Background: Determine the potential role for protons in the preoperative treatment of resectable rectal cancer. METHODS Eight consecutive patients with resectable (T2-T3) rectal cancers underwent 3D conformal photon (3DCRT); intensity-modulated photon (IMRT); and 3D conformal proton (PT) treatment planning. Initial target volumes (PTV1) were contoured using the RTOG anorectal atlas guidelines. Boost target volumes (PTV2) consisted of the gross rectal tumor plus a uniform 2cm expansion. Plans delivered 45Gray (Gy) or Cobalt Gray Equivalent (CGE) to the PTV1 and a 5.4 Gy (CGE) boost to the PTV2. Ninety-five percent of PTVs received 100% of the target dose and 100% of the PTVs received 95% of the target dose. Standard normal tissue constraints were utilized. Wilcoxon paired t-tests were performed to compare various dosimetric points between the 3 plans for each patient. RESULTS All plans met all normal-tissue constraints and were isoeffective in terms of PTV coverage. Proton plans offered significantly reduced median normal-tissue exposure over the 3DCRT and IMRT plans with respect to: pelvic bone marrow (PBM) at the V5Gy, V10Gy, V15Gy and V20Gy levels and small bowel (SB) at the V10Gy and V20Gy levels. Proton plans also offered significantly reduced median normal-tissue exposure over the 3DCRT plans with respect to the SB at the V30Gy and V40Gy levels. CONCLUSIONS 1.) By reducing bone marrow exposure, protons may reduce the acute hematologic toxicity of neoadjuvant chemoradiation and increase the likelihood of uninterrupted chemotherapy delivery. Bone marrow sparing may also facilitate the delivery of salvage chemotherapy for patients who go on to develop hematogenous metastasis. 2.) By reducing small bowel exposure, protons may reduce toxicity and possibly facilitate the use of more aggressive concomitant chemotherapy with radiotherapy. [Table: see text].

A retrospective review of demographics and stage of presentation in patients with ER/PR/Her2-neu receptor negative breast cancer.

Abstract #2097 Background: Estrogen receptor/progesterone receptor/Her2-neu receptor negative, or “triple negative” breast cancer (TNBC) is notable for its propensity to metastasize early and display a comparatively more aggressive course. Some estimates comprise approximately 15-20% of all breast cancers, and it is apparently more prevalent in African-American women, Hispanic women, and women younger than 40 years of age. There has been a continual decline in death rates due to breast cancer since 1990 attributed to both earlier detection, as well as better treatment modalities including hormonal blockade in estrogen- and progesterone-receptor positive cancers, as well as the anti-Her2/neu receptor antibody, Trastuzumab. These hormone receptors are not found in TNBC, and therefore the traditional targets for endocrine manipulation cannot be therapeutically exploited. While lower socioeconomic status and racial predisposition to this aggressive disease have been observed, there exists a paucity of research into other demographic risk factors or associations. Methods: We reviewed data between January 2000 to December 2005 from our tumor registry with particular attention to age, race, family history, tobacco use, and stage of presentation, comparing this subset of patients (n=39) to other records (n=303). We included only those patients in whom the status of all three receptors were recorded. Results: Comparisons were made for TNBC vs non-TNBC patients respectively as follows: mean age (59.87±15.67 yrs vs 60.09±13.98 yrs); Black, 58.97% vs 39.27%; White, 35.90% vs 57.76%; Other minorities, 2.56% vs 0.99%; Unknown, 2.56% vs 0.33%. Comparisons with respect to tobacco history for TNBC vs non-TNBC patients respectively: cigarettes, 15.38% vs 18.81%; non smokers, 71.79% vs 61.72%; ex smokers, 5.13% vs 8.91%; chewing tobacco, 0% vs 0.33% and unknown, 7.69% vs 10.23%. Positive family history of cancer, 30.77% vs 33.33%; no family history of cancer, 51.28% vs 51.82%, and unknown, 17.95% vs 14.85%. Pathologic stage at diagnosis for TNBC vs non-TNBC patients respectively: Stage 0, 15.79% vs 11.37%; stage 1, 34.21% vs 30.98%; stage 2, 28.98% vs 37.25%; stage 3, 18.42% vs 17.25%, and stage 4, 3.63% vs 3.14%. Analysis using χ 2 test (χ 2 =0.855) and CMH test for Linear Trend analysis (p=0.4775) showed no difference in percentages in association with the 5 stages or TNBC status and no linear trend respectively. Conclusion: This data suggests that at our institution, TNBC is less prevalent (12.87%) than estimates of 15-20% published in other studies. There was no difference in age at diagnosis (p=0.9272), with black patients more likely to have TNBC (p=0.004, OR=2.755). There was no significant association between smoking status and TNBC (p=0.4385). There was no significant association between a family history of cancer and TNBC (p=0.8384). When accounting for samples size, TNBC was as prevalent as non TNBC at all stages of diagnosis (p=0.4332, p=0.6890, p=0.3205, p=0.8591, and p=0.8651 respectively). These results differ from other published data and may reflect differences in statistical analysis or patient population. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2097.