Modern induction chemotherapy before chemoradiation for bulky locally-advanced nonsmall cell lung cancer improves survival.

BACKGROUND: We seek to investigate whether carboplatin-based induction chemotherapy before modern day concurrent chemoradiotherapy (CCRT) improves survival in patients with bulky, locally advanced nonsmall cell lung cancer (NSCLC). MATERIALS AND METHODS: This analysis included 105 patients with Stage II and III NSCLC treated with definitive CCRT from 2003 to 2013. All patients underwent definitive treatment with weekly platinum-based doublet chemotherapy delivered concurrently with 60-66 Gy of thoracic radiotherapy. Thirty patients who received induction chemotherapy before CCRT had T4 disease, N3 disease, or gross tumor volume (GTV) of >150 cm 3. These patients were compared to those with unresectable disease who received CCRT alone without induction chemotherapy. Statistical analysis included univariate and multivariate methods. RESULTS: Mean follow-up time was 15.6 months. Patients treated with carboplatin based induction chemotherapy demonstrated prolonged overall survival (28.2 vs. 14.2 months, P = 0.04), progression free survival (12.6 vs. 9.0 months, P = 0.02), and distant metastasis free survival (15.8 vs. 10.1months, P = 0.05) compared to those who received CCRT alone without induction chemotherapy. Univariate analysis revealed older age, larger GTV, and squamous pathology as negative prognostic factors. When controlling for these factors, Cox regression analysis indicated a trend toward significantly improved overall survival in the induction cohort (P = 0.10). CONCLUSION: In patients with large tumors or bulky nodal NSCLC, carboplatin-based induction chemotherapy may be an important addition to definitive CCRT in the modern era. Our findings strongly support further investigation induction chemotherapy in this population.

Impact of metformin use on survival in locally-advanced, inoperable non-small cell lung cancer treated with definitive chemoradiation.

BACKGROUND: We investigated survival outcomes in diabetic patients with non-small cell lung cancer (NSCLC) treated with concurrent metformin and definitive chemoradiation. METHODS: This single-institution, retrospective cohort study included 166 patients with NSCLC who were treated definitively with chemoradiation between 1999 and 2013. Of 40 patients who had type II diabetes, 20 (50%) were on metformin, and 20 (50%) were not on metformin. The primary outcome was overall survival (OS), and secondary outcomes included progression-free survival (PFS), locoregional recurrence-free survival (LRRFS) and distant metastasis-free survival (DMFS). Kaplan Meier method and log-rank test were performed in survival analysis. Cox regression was utilized in univariate analysis of potential confounders. RESULTS: Median follow-up was 17.0 months. Compared with non-diabetic patients, diabetic patients on metformin demonstrated similar OS (16.3 vs. 14.3 mo, P=0.23), PFS (11.6 vs. 9.7 mo, P=0.26), LRRFS (14.1 vs. 11.9 mo, P=0.78), and DMFS (13.4 vs. 10.0 mo, P=0.69). Compared with diabetic patients not on metformin, diabetic patients on metformin also exhibited similar OS (14.3 vs. 19.2 mo, P=0.18), PFS (19.7 vs. 10.1 mo, P=0.38), LRRFS (11.9 vs. 15.5 mo, P=0.69), and DMFS (10.0 vs. 17.4 mo, P=0.12). Identified negative prognostic factors on included squamous cell histology, lower performance status, higher T stage, and non-caucasian ethnicity. CONCLUSIONS: No statistically significant differences in survival or patterns of failure were found among the three cohorts in this small set of patients. No statistically significant differences in survival or patterns of failure were found between the three cohorts in this small set of patients. Though it is possible that metformin use may in fact have no effect on survival in NSCLC patients treated with definitive RT, larger-scale retrospective and prospective studies are implicated for clarification.

Cranial irradiation in adults diagnosed with acute myelogenous leukemia presenting with hyperleukocytosis and neurologic dysfunction.

This study describes our institution's experience using whole brain radiation therapy (WBRT) to treat patients with acute myelogenous leukemia (AML) presenting with hyperleukocytosis. After approval by the institutional review board, we identified patients with AML and hyperleukocytosis using hospital records. The primary endpoints in the study included alleviation of neurological symptoms (or prevention if prophylactic RT was used), overall survival, development of intracranial hemorrhage (ICH) and ≥ grade 3 toxicities using the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0). Eighteen patients received WBRT for the treatment of AML hyperleukocytosis. Thirteen patients received treatment in order to control neurological symptoms. Clinical assessment showed that 12 of 13 patients (92%) achieved resolution of neurological symptoms either concurrent with RT or immediately after RT. The mean overall survival for all of the patients who received WBRT was 14.2 months (95% confidence interval, 5.4-23.0). No patient who received RT experienced ≥ grade 3 toxicity. Two (6%) patients developed ICH following therapy. Our institution's experience demonstrates that WBRT may be utilized as part of multimodality therapy in order to alleviate or prevent neurological symptoms in patients with AML presenting with leukostasis.

Improvement in interobserver accuracy in delineation of the lumpectomy cavity using fiducial markers.

PURPOSE: To determine, whether the presence of gold fiducial markers would improve the inter- and intraphysician accuracy in the delineation of the surgical cavity compared with a matched group of patients who did not receive gold fiducial markers in the setting of accelerated partial-breast irradiation (APBI). METHODS AND MATERIALS: Planning CT images of 22 lumpectomy cavities were reviewed in a cohort of 22 patients; 11 patients received four to six gold fiducial markers placed at the time of surgery. Three physicians categorized the seroma cavity according to cavity visualization score criteria and delineated each of the 22 seroma cavities and the clinical target volume. Distance between centers of mass, percentage overlap, and average surface distance for all patients were assessed. RESULTS: The mean seroma volume was 36.9 cm(3) and 34.2 cm(3) for fiducial patients and non-fiducial patients, respectively (p = ns). Fiducial markers improved the mean cavity visualization score, to 3.6 ± 1.0 from 2.5 ± 1.3 (p < 0.05). The mean distance between centers of mass, average surface distance, and percentage overlap for the seroma and clinical target volume were significantly improved in the fiducial marker patients as compared with the non-fiducial marker patients (p < 0.001). CONCLUSIONS: The placement of gold fiducial markers placed at the time of lumpectomy improves interphysician identification and delineation of the seroma cavity and clinical target volume. This has implications in radiotherapy treatment planning for accelerated partial-breast irradiation and for boost after whole-breast irradiation.

Cord Compression due to Extramedullary Hematopoiesis in an Adolescent with Known Beta Thalassemia Major.

We describe a 16 year-old male with ß thalassemia major and gait disturbances that had not been given blood transfusions due to a severe childhood transfusion reaction. Thoracic spine MRI demonstrated hematopoietic marrow throughout the spine and epidural masses causing cord compression consistent with extramedullary hematopoiesis (EMH). After treatment with steroids, radiotherapy and monitored blood transfusions, the patient demonstrated significant improvement of his paraspinal lesions and near complete resolution of his neurological symptoms. While EMH causing cord compression in adolescents is rare in the current era of bone marrow transplantation or chronic transfusions, it should be considered when thalassemia major patients present with neurological deficits. The well defined imaging features of EMH can play a central role in its diagnosis and management, especially because surgical and / or radiotherapeutic intervention are often considered in cases of failed medical treatment.

A pilot study of allogeneic cellular therapy for patients with advanced hematologic malignancies.

Allogeneic hematopoietic stem cell transplantation provides curative therapy for some patients with advanced hematologic malignancies. Disease response after allogeneic transplant is, at least in part, mediated by donor immune cells. In this report we describe a cellular therapy using haploidentical peripheral blood stem cells administered after very low dose total body irradiation (TBI) (100cGy). The donor cells were anticipated to be rejected, so no graft-versus-host (GVHD) prophylaxis was used. Patients with persistent disease beyond 8 weeks could be further treated with infusions of irradiated haploidentical donor cells. Of the 10 patients enrolled in the study, durable engraftment of allogeneic cells was seen in one patient. Two patients with resistant relapsed acute myelogenous leukemia (AML) had a disease response. Analysis of T cell reactivity from one patient who achieved a complete response but did not have durable engraftment of donor cells indicated that disease response was associated with the generation of host-derived anti-leukemic cytotoxic CD8+ T cells that reacted with an AML-associated proteinase 3 epitope. Results from this patient suggest that allogeneic therapy induced a host anti-tumor response associated with cytotoxic T cells reactive with a low affinity self-antigen.

Intensity-modulated radiation therapy for orbital lymphoma.

PURPOSE: Orbital manifestations of non-Hodgkin's lymphoma (NHL) are rare and accounts for only 1% of all cases of NHL. There have been no reports of treating orbital lymphoma using intensity-modulated radiotherapy (IMRT). MATERIALS AND METHODS: Four patients were treated at our institution for orbital lymphoma using IMRT. Radiotherapy (RT) plans using wedged pair fields were developed for comparison. Clinical results using IMRT are presented and a dosimetric analysis between IMRT and RT was performed. RESULTS: All patients had a complete response based on their physical examinations and post-IMRT imaging. Symptoms that had been present at initial presentation resolved in all patients during the course of the treatment. All four patients experienced only grade 1 dry eye syndrome and keratitis. The average dose to the contralateral orbit, lacrimal gland, and lens were all significantly reduced (P < 0.01) in IMRT patients as compared to the RT patients. IMRT reduced the V5 and V10 for the contralateral lens, orbit, and lacrimal gland and the optic chiasm (P < 0.05). CONCLUSION: IMRT is feasible when treating orbital lymphoma and reduces dose to critical structures while providing excellent dose coverage of target volumes. IMRT offers patients with orbital lymphoma excellent clinical outcomes, similar to conventional RT, with no increased toxicity.