Joseph W. Leach

Bisphosphonate-Related Osteonecrosis of the Jaw: Clinical Features, Risk Factors, Management, and Treatment Outcomes of 26 Patients

PURPOSE To report the clinical features, risk factors, management, and treatment outcomes of nitrogen-containing bisphosphonate (n-BIS)-related osteonecrosis of the jaw (BRONJ). PATIENTS AND METHODS Patients with suspected BRONJ were referred to the School of Dentistry for evaluation and treatment. RESULTS A total of 26 patients (9 men and 17 women, mean age 64 years) were diagnosed with BRONJ. Of the 26 patients, 23 had received n-BIS therapy for cancer and 3 for osteoporosis. BRONJ lesions were noted more frequently in the mandible and in the posterior sextants. Of the 26 patients, 16 had developed BRONJ after dentoalveolar procedures, and 10 had developed it spontaneously. The mean interval to development of BRONJ was shorter in the patients with cancer receiving intravenous n-BIS than in the patients with osteoporosis receiving oral n-BIS (37.1 versus 77.7 months, P = .02). Using the American Association of Oral and Maxillofacial Surgeons staging system, 2 patients were diagnosed with stage I lesions, 19 with stage II, and 5 with stage III lesions. The initial management of BRONJ was nonsurgical, with debridement performed at subsequent visits, if needed. The BRONJ lesions healed completely in 4 patients, healed partially in 8, remained stable in 7, and progressed in 7. The spontaneous lesions responded favorably to BRONJ management compared with lesions that developed after dentoalveolar procedures (P = .01). No significant difference was found in response to BRONJ management between patients who had continued or discontinued n-BIS therapy after the BRONJ diagnosis (P = .54). CONCLUSIONS Long-term n-BIS therapy and recent dental procedures are consistent findings in patients with BRONJ. Spontaneous BRONJ lesions respond favorably to current BRONJ treatment strategies.

Case-Control Study to Evaluate Predictors of Lymphedema After Breast Cancer Surgery

PURPOSE/OBJECTIVES To identify risk factors for lymphedema after breast cancer surgery. DESIGN Multisite case-control study. SETTING Lymphedema clinics in the upper midwestern region of the United States. SAMPLE 94 patients with lymphedema and 94 controls without lymphedema, matched on type of axillary surgery and surgery date. METHODS The Measure of Arm Symptom Survey, a patient-completed tool, assessed potential risk factors for lymphedema. Severity of lymphedema was measured by arm circumference, and disease and treatment factors were collected via chart review. MAIN RESEARCH VARIABLES Risk factors for lymphedema after breast cancer surgery. FINDINGS On univariate analysis, patients with lymphedema were more likely than controls to be overweight (body mass index >or= 25) (p = 0.009). They also were more likely to have had axillary radiation (p = 0.011), mastectomy (p = 0.008), chemotherapy (p = 0.033), more positive nodes (p = 0.009), fluid aspirations after surgery (p = 0.005), and active cancer status (p = 0.008). Strength training (p = 0.014) and air travel (p = 0.0005) were associated with less lymphedema occurrence. On multivariate analysis, the only factor significantly associated with lymphedema was being overweight (p = 0.022). CONCLUSIONS Being overweight is an important modifiable risk factor for lymphedema. Axillary radiation, more extensive surgery, chemotherapy, and active cancer status also were predictive of lymphedema. IMPLICATIONS FOR NURSING This study provides evidence that excess weight contributes to lymphedema; strength training and airline travel did not contribute to lymphedema.

A retrospective study evaluating frequency and risk factors of osteonecrosis of the jaw in 576 cancer patients receiving intravenous bisphosphonates

ObjectiveTo evaluate the frequency, risk factors, and clinical presentation of bisphosphonate (BP)-related osteonecrosis of the jaw (BRONJ). Study DesignWe performed a retrospective analysis of 576 patients with cancer treated with intravenous pamidronate and/or zoledronate between January, 2003 and December, 2007 at the University of Minnesota Masonic Cancer Center and Park Nicollet Institute. ResultsEighteen of 576 identified patients (3.1%) developed BRONJ including 8 of 190 patients (4.2%) with breast cancer, 6 of 83 patients (7.2%) with multiple myeloma, 2 of 84 patients (2.4%) with prostate cancer, 1 of 76 patients (1.3%) with lung cancer, 1 of 52 patients (1.9%) with renal cell carcinoma, and in none of the 73 patients with other malignancies. Ten patients (59%) developed BRONJ after tooth extraction, whereas 7 (41%) developed it spontaneously (missing data for 1 patient). The mean number of BP infusions (38.1±19.06 infusions vs. 10.5±12.81 infusions; P<0.001) and duration of BP treatment (44.3±24.34 mo vs. 14.6±18.09 mo; P<0.001) were significantly higher in patients with BRONJ compared with patients without BRONJ. Multivariate Cox proportional hazards regression analysis showed that diabetes [hazard ratio (HR)=3.40; 95% confidence interval (CI), 1.14-10.11; P=0.028], hypothyroidism (HR=3.59; 95% CI, 1.31-9.83; P=0.013), smoking (HR=3.44; 95% CI, 1.28-9.26; P=0.015), and higher number of zoledronate infusions (HR=1.07; 95% CI, 1.03-1.11; P=0.001) significantly increased the risk of developing BRONJ. ConclusionsIncreased cumulative doses and long-term BP treatment are the most important risk factors for BRONJ development. Type of BP, diabetes, hypothyroidism, smoking, and prior dental extractions may play a role in BRONJ development.

Anxiety and Health-Related Quality of Life Among Patients With Low–Tumor Burden Non-Hodgkin Lymphoma Randomly Assigned to Two Different Rituximab Dosing Regimens: Results From ECOG Trial E4402 (RESORT)

PURPOSE The purpose of this study was to compare illness-related anxiety among participants in the Rituximab Extended Schedule or Retreatment Trial (RESORT) randomly assigned to maintenance rituximab (MR) versus rituximab re-treatment (RR). A secondary objective was to examine whether the superiority of MR versus RR on anxiety depended on illness-related coping style. PATIENTS AND METHODS Patients (N = 253) completed patient-reported outcome (PRO) measures at random assignment to MR or RR (baseline); at 3, 6, 12, 24, 36, and 48 months after random assignment; and at rituximab failure. PRO measures assessed illness-related anxiety and coping style, and secondary end points including general anxiety, worry and interference with emotional well-being, depression, and health-related quality of life (HRQoL). Patients were classified as using an active or avoidant illness-related coping style. Independent sample t tests and linear mixed-effects models were used to identify treatment arm differences on PRO end points and differences based on coping style. RESULTS Illness-related anxiety was comparable between treatment arms at all time points (P > .05), regardless of coping style (active or avoidant). Illness-related anxiety and general anxiety significantly decreased over time on both arms. HRQoL scores were relatively stable and did not change significantly from baseline for both arms. An avoidant coping style was associated with significantly higher anxiety (18% and 13% exceeded clinical cutoff points at baseline and 6 months, respectively) and poorer HRQoL compared with an active coping style (P < .001), regardless of treatment arm assignment. CONCLUSION Surveillance until RR at progression was not associated with increased anxiety compared with MR, regardless of coping style. Avoidant coping was associated with higher anxiety and poorer HRQoL.

Phase II study of topotecan and bevacizumab in advanced, refractory non-small-cell lung cancer

BACKGROUND This clinical trial evaluated whether topotecan in combination with bevacizumab improved progression-free survival (PFS) in patients with advanced, refractory non--small-cell lung cancer in a second-line setting. PATIENT AND METHODS Patients aged 18 years old and older received topotecan (4.0 mg/m(2)) on days 1, 8, and 15, and bevacizumab (10 mg/kg) on days 1 and 15 as intravenous infusions on a 28-day treatment cycle. Available tumor specimens were analyzed for ISG15 gene expression as a biomarker of response to topotecan. RESULTS Forty-two patients were enrolled in the study, with a median age of 62.5 years and a median of 3 (range, 1-7) prior treatment regimens. Almost half (n = 18, 42.9%) of the patients received prior bevacizumab therapy. PFS was 5.1 months (95% CI, 3.7-7.8 months), and overall survival was 11.5 months (95% CI, 6.8-15.5 months). Response rates were as follows: 14.3% partial response, 54.8% stable disease, and 28.6% progressive disease. Hematologic toxicities included grade 3 thrombocytopenia (n = 7, 16.7%), neutropenia (n = 4, 9.5%), and anemia (n = 2, 4.8%). One toxic death occurred due to pulmonary hemorrhage, and one patient experienced a grade 4 pulmonary embolism. Grade 3 nonhematologic adverse events were uncommon (< 8%). There was a trend for improved median PFS, 3.5 months vs. 1.8 months (P = .26), in patients with high ISG15 expression. CONCLUSION Bevacizumab in combination with topotecan as a salvage therapy for metastatic non--small-cell lung cancer is well tolerated and is worthy of further investigation.

A prospective cohort study of patients with peripheral T-cell lymphoma in the United States

Long‐term survival in patients with aggressive peripheral T‐cell lymphoma (PTCL) is generally poor, and there currently is no clear consensus regarding the initial therapy used for these diseases. Herein, the authors analyzed treatment patterns and outcomes in a prospectively collected cohort of patients with a new diagnosis of nodal PTCL in the United States.

Analysis of Peripheral T-cell Lymphoma Diagnostic Workup in the United States

Micro‐Abstract With increased understanding of the unique entities of peripheral T‐cell lymphoma (PTCL), subtype‐specific approaches are emerging, and more precise diagnoses are becoming increasingly important. Using data from a large prospective cohort study, we examined the diagnostic patterns of PTCL in the United States. We found that the workup for PTCL varies widely and often lacks important phenotypic information to fully characterize the lymphoma. Background: With increased understanding of the unique entities, subtype‐specific approaches for peripheral T‐cell lymphoma (PTCL) are emerging, and more precise diagnoses are becoming increasingly important. Patients and Methods: We analyzed the approach to the histopathologic diagnosis of PTCL using data from the comprehensive oncology measures of peripheral T‐cell lymphoma (COMPLETE) study. The COMPLETE trial is a large prospective cohort study of patients with newly diagnosed PTCL in the United States. Results: A total of 499 patients were enrolled from 40 academic and 15 community‐based centers. Baseline assessment forms were collected for 493 patients, of which 435 (88%) were available for analysis. The most common diagnoses were PTCL, not otherwise specified (PTCL‐NOS), anaplastic large cell lymphoma, and angioimmunoblastic T‐cell lymphoma (AITL). A mean of 10 markers (range, 0‐21) was assessed per patient. CD30 was assessed frequently but not uniformly in cases that were not anaplastic large cell lymphoma. Only 17% of PTCL‐NOS cases were assessed for PD1. CXCL13 was a relatively sensitive marker in AITL, expressed in 84% of tested cases; however, only 3% of PTCL‐NOS cases were tested. T follicular helper cell marker assessment differed between academic and community practices, with PD1 more often evaluated by academic centers in cases of AITL (62% vs. 12%; P = .01). Conclusion: The diagnostic workup for PTCL in the United States varies widely and often lacks important phenotypic information to fully characterize the lymphoma. Gaps in testing of selected markers should be filled, given the impending revision to the World Health Organization classification. The accuracy of diagnosis will become increasingly important as we enter the era of targeted treatment for PTCL.

Tumor histopathology predicts outcomes after resection of colorectal cancer liver metastases treated with and without pre-operative chemotherapy.

Study objectives, included determination of: (i) associations between radiologic and pathologic responses of colorectal cancer liver metastases (CRCLM) to chemotherapy; and (ii) whether CRCLM histopathology is associated with recurrence free survival (RFS) after resection among patients not treated with pre‐operative chemotherapy (untreated).

Clinicopathologic analysis of a large series of microinvasive breast cancers

Clinical management of microinvasive breast cancer (Tmic) remains controversial. Although metastases are infrequent in Tmic carcinoma patients, surgical treatment typically includes lymph node sampling. The objective of this study was to determine the rate and predictors of lymph node metastases, recurrence, and survival in a large series of Tmic breast carcinomas. Consecutive cases of Tmic were identified within our health care system from 2001 to 2015. We reviewed results of lymph node sampling and other pathologic factors including hormone receptor/HER2 status, associated in situ tumor size/grade, margin status, number of invasive foci, surgical/adjuvant therapies, and recurrence/survival outcomes. In this cohort, 294 Tmic cases were identified with mean follow‐up of 4.6 years. Of 260 patients who underwent axillary staging, lymph node metastases were identified in 1.5% (all of which were ductal type). All Tmic cases with positive lymph node metastases had associated DCIS with size > 5 cm (5.3‐8.5 cm) compared to a median DCIS tumor size of 2.5 cm (0.2‐19.0 cm) for the entire cohort. No lymph node metastases were seen with microinvasive lobular carcinoma. During the follow‐up period, there were no regional/distant recurrences or breast cancer‐associated deaths in a mean follow‐up period of 4.6 years. Two patients developed subsequent ipsilateral breast cancer (DCIS) in a different quadrant than the original Tmic. Clinical behavior of microinvasive breast cancer in this series is similar to DCIS. Lymph node metastases are uncommon and were only seen with ductal type microinvasive carcinoma. Our data suggest limited benefit for routine node sampling and support management of Tmic similar to DCIS, particularly for patients with DCIS < 5 cm in size.

Phase II study of topotecan and bevacizumab in advanced refractory non-small cell lung cancer (NSCLC).

7563 Background: Bevacizumab in combination with carboplatin and paclitaxel improves survival of patients with NSCLC in a first-line setting. We hypothesized that non-cross-resistant, second-line salvage therapy with the topoisomerase 1 inhibitor, topotecan, in combination with bevacizumab would have activity in NSCLC. METHODS Forty-two patients were enrolled between 10/2006-9/2010. Patients received topotecan 4.0 mg/m2 on days 1, 8 and 15 and bevacizumab 10 mg/kg on days 1 and 15 as IV infusions. Treatment was repeated every 28 days in the absence of disease progression or unacceptable toxicity. Eligibility criteria included age older than 18 years, ECOG PS of 0-1, and adequate organ function. Patients with treated brain metastases were permitted to enter this study. Response assessment (using RECIST) was performed every two cycles. Primary endpoint of this study was progression-free survival (PFS). RESULTS Forty-two patients were enrolled in the study. Median age was 60.6 years (range = 36-81). Patients had a median of 3 prior treatment regimens (range 1-7), and 93% had prior platinum therapy. The primary objective of PFS was 238 days (95% CI, 117-332 days). Overall survival (OS) was 345 days (95% CI, 213-464 days). Response rates were as follows: 14.3% partial response (PR), 54.8% stable disease (SD), 28.6% progressive disease (PD). Grade 3 hematologic toxicities seen in participants included thrombocytopenia (16.7%), neutropenia (9.5 %), and anemia (4.8%). There was no grade 4 or higher hematologic toxicities. Only one toxic death, due to pulmonary hemorrhage, occurred during the study. The only grade 4 toxicity was a pulmonary embolism in one patient. Grade 3 non-hematologic adverse events were minimal (<8%) and included: hyperglycemia, bone pain, gastroesophageal reflux, diarrhea, infection, shortness of breath, bowel obstruction, DVT, abdominal pain, pseudogout, and SVC thrombosis. CONCLUSIONS The combination of bevacizumab and topotecan as a salvage therapy for metastatic NSCLC appears to be well tolerated and provides significant progression-free survival. A randomized trial should be performed to compare this combination with other NSCLC regimens.