Prophylactic Breast Irradiation for Prevention of Bicalutamide-induced Painful Gynecomastia in Patients with Low- and Intermediate-risk Prostate Cancer.

BACKGROUND: Bicalutamide monotherapy (BMT) is an option for androgen deprivation therapy (ADT) in patients with low- and intermediate-risk prostate cancer (LIR-PC). Painful gynecomastia (PG) is a common side effect of BMT. Few therapeutic options are available for preventing BMT-induced PG. OBJECTIVES: To assess the efficacy and side effects of single fraction (SF) prophylactic breast irradiation (PBI) to prevent painful gynecomastia (PG) in patients LIR-PC treated with BMT. METHODS: We reviewed the results of bilateral PBI in a prospective cohort of LIR-PC patients who received 150 mg bicalutamide daily as a first-line treatment for at least 12 months. A single fraction of 8 Gy was administered to both breasts by a stationary field of 10 × 10 cm, using 10-15 MeV electron beam. PBI was commenced on the same day as BMT, but prior to the first dose of bicalutamide. A radiotherapy treatment plan was designed to cover breast tissue by the 90% isodose line. Subsequent monthly physical examinations were scheduled for all patients during the first year of BMT to evaluate any PG symptoms. RESULTS: Seventy-six patients received BMT and PBI, 80% (61/76) showed no signs of PG; 20% (15/76) experienced mild gynecomastia. The main adverse effect of PBI was grade 1 radiation dermatitis. CONCLUSIONS: PBI using a SF of 8 Gy is an effective, safe, and low-cost strategy for the prevention of BMT-induced PG in LIR-PC patients.

Neoadjuvant Osimertinib Followed by Sequential Definitive Radiation Therapy and/or Surgery in Stage III Epidermal Growth Factor Receptor-Mutant Non-Small Cell Lung Cancer: An Open-Label, Single-Arm, Phase 2 Study.

PURPOSE: The treatment for unresectable, locally advanced stage III non-small cell lung cancer (NSCLC) is concurrent chemoradiation therapy (CRT) followed by consolidation durvalumab. This study aimed to evaluate the benefit of neoadjuvant osimertinib as an alternative therapy to this approach with the aim of reducing the radiation field. METHODS AND MATERIALS: This investigation was a nonrandomized, open-label, single-arm, phase 2, prospective, proof-of-concept study. Eligible patients were classified as having treatment-naïve, nonoperable, stage III epidermal growth factor receptor-mutant NSCLC. Patients received 80 mg of oral osimertinib daily for 12 weeks before definitive radiation therapy (RT) and/or surgery. The response was assessed at weeks 6 and 12. For responders, sequential definitive RT and/or surgery were planned. Nonresponders were started on standard CRT. After RT ± surgery or CRT, patients were followed for 2 years without adjuvant therapy. The primary endpoint was the objective response rate (ORR), with September 20, 2022, set as the cut-off for data collection. Secondary endpoints were safety and the gross tumor volume (GTV), planned tumor volume (PTV), and the percentage of total lung volume minus GTV exceeding 20 Gy (V20%) before versus after osimertinib. Exploratory analyses included assessments of the presence of plasma circulating tumor-free DNA (ctDNA) before osimertinib treatment, at weeks 6 and 12, at the end of RT, and 6 weeks post-RT. RESULTS: Twenty-four patients were included (19 women; median age, 73 years; range, 51-82 years). Nineteen of 24 had never smoked, 20 of 24 had adenocarcinoma, 16 of 24 had exon 19 deletions, and 8 of 24 had exon 21 mutations. Participants had stage IIIA (10), IIIB (9), or IIIC (5) disease. Three patients were excluded from the analysis (1 dropped out and 2 were still undergoing osimertinib treatment at the cut-off date). The ORR to induction osimertinib was 95.2% (17 partial response, 3 complete response, and 1 progressive disease). After induction osimertinib, 13 of 20 patients were definitively radiated, 3 of 20 underwent surgery, and 5 of 20 were excluded. Four patients were restaged as stage IV (contralateral ground-glass opacities responded to osimertinib), and 1 patient withdrew informed consent. Three patients underwent surgery, one of whom was treated with RT. Two patients achieved pT1aN0, and one achieved pathologic complete response. The median GTV, PTV, and V20% before osimertinib treatment were 47.4 ± 76.9 cm3 (13.5-234.9), 227.0 ± 258.8 cm3 (77.8-929.2), and 27.1 ± 16.4% (6.2-60.3), respectively. The values after osimertinib treatment were 27.5 ± 42.3 cm3 (2.99-137.7; -48 ± 20%; P = .02), 181.9 ±198.4 cm3 (54-718.1; -31 ± 20%; P = .01), and 21.8 ± 11.7% (9.1-44.15; -24 ± 40%; P = .04), respectively. PTV/GTV/V20% reduction was associated with tumor size and central location. The median follow-up time was 28.71 months (range, 0.4-45.1 months), and median disease-free survival was not reached (mean, 30.59; standard error, 3.94; 95% confidence interval, 22.86-38.31). ctDNA was detected in 5 patients; 4 of 5 were positive for ctDNA at baseline and became negative during osimertinib induction but were again positive after osimertinib treatment was terminated. Interestingly, 3 patients who were ctDNA negative at baseline became weakly positive after RT and then were negative at follow-up. No significant adverse events were reported during the osimertinib or radiation phases. CONCLUSIONS: Neoadjuvant osimertinib therapy is feasible in patients with stage III lung cancer NSCLC, followed by definitive radiation and/or surgery, with an ORR of 95.2% and an excellent safety profile. Osimertinib induction for 12 weeks before definitive radiation (chemo-free) significantly reduced the radiation field by nearly 50% with a linear association with tumor size. Further studies are needed to test this chemo-free approach for long-term outcomes before practices are changed.

Safety of the BNT162b2 mRNA COVID-19 vaccine in oncologic patients undergoing numerous cancer treatment options: A retrospective single-center study.

ABSTRACT: The COVID-19 pandemic, caused by the SARS-CoV2 virus, has infected millions worldwide with cancer patients demonstrating a higher prevalence for severe disease and poorer outcomes. Recently, the BNT162b2 mRNA COVID-19 vaccine was released as the primary means to combat COVID-19. The currently reported incidence of local and systemic side effects was 27% in the general public. The safety of the BNT162b2 mRNA COVID-19 vaccine has not been studied in patients with an active cancer diagnosis who are either ongoing or plan to undergo oncologic therapy.This single center study reviewed the charts of 210 patients with active cancer diagnoses that received both doses of the BNT162b2 mRNA COVID-19 vaccine. The development of side effects from the vaccine, hospitalizations or exacerbations from various oncologic treatment were documented. Type of oncologic treatment (immunotherapy, chemotherapy, hormonal, biologic, radiation or mixed) was documented to identify if side effects were related to treatment type. The time at which the vaccine was administered in relation to treatment onset (on long term therapy, within 1 month of therapy or prior to therapy) was also documented to identify any relationships.Sixty five (31%) participants experienced side effects from the BNT162b2 mRNA COVID-19 vaccine, however most were mild to moderate. Treatment protocol was not linked to the development of vaccine related side effects (P = .202), nor was immunotherapy (P = .942). The timing of vaccine administered in relation to treatment onset was also not related to vaccine related side effects (P = .653). Six (2.9%) participants were hospitalized and 4 (2%) died.The incidence of side effects in cancer patients is similar to what has been reported for the general public (31% vs 27%). Therefore, we believe that the BNT162b2 mRNA COVID-19 vaccine is safe in oncologic patients undergoing numerous cancer treatments.

Epithelioid Hemangioendothelioma and Epithelioid Hemangioma: Pazopanib as a Potential Salvage Therapy.

Epithelioid hemangioma (EH) and epithelioid hemangioendothelioma (EHE) are both rare vascular tumors. EH tumors are often benign while EHE tumors have moderate malignant potential. Here, we present three unique cases at Soroka Medical Center, two featuring EH of the bone and one presenting EHE of the mediastinum. Each case demonstrates distinct treatment challenges due to the rarity of both diseases and lack of established guidelines. We propose three treatment approaches including pazopanib for salvage therapy of EH of the bone and minimally invasive surgical resection which in these cases lead to complete symptom relief and tumor stabilization upheld over time with close follow-up.

Hemoglobin Levels and Red Blood Cells Distribution Width Highlights Glioblastoma Patients Subgroup With Improved Median Overall Survival.

Glioblastoma multiforme (GBM) is known for its dismal prognosis, though its dependence on patients' readily available RBCs parameters is not fully established. In this work, 170 GBM patients, diagnosed and treated in Soroka University Medical Center (SUMC) over the last 12 years were retrospectively inspected for their survival dependency on pre-operative RBCs parameters. Besides KPS and tumor resection supplemented by oncological treatment, age under 70 (HR = 0.4, 95% CI 0.24-0.65, p = 0.00073), low hemoglobin level (HR = 1.79, 95% CI 1.06-2.99, p = 0.031), and Red Cell Distribution Width (RDW) < 14% (HR = 0.57, 95% CI 0.37-0.88, p = 0.018) were found to be prognostic of patients' overall survival in multivariate analysis, accounting for a false discovery rate of < 5% due to multiple hypothesis testing. According to these results, a stratification tree was made, from which a favorable route highlighted a subgroup of nearly 30% of the cohorts' patients whose median overall survival was 21.1 months (95% CI 16.2-27.2)-higher than the established chemo-radiation standard first-line treatment regimen overall median survival average of about 15 months. The beneficial or detrimental effect of RBCs parameters on GBM prognosis and its possible causes is discussed.

Dyspnea in Patients Receiving Radical Radiotherapy for Non-Small Cell Lung Cancer: A Prospective Study.

BACKGROUND AND PURPOSE: Dyspnea is an important symptomatic endpoint for assessment of radiation-induced lung injury (RILI) following radical radiotherapy in locally advanced disease, which remains the mainstay of treatment at the time of significant advances in therapy including combination treatments with immunotherapy and chemotherapy and the use of local ablative radiotherapy techniques. We investigated the relationship between dose-volume parameters and subjective changes in dyspnea as a measure of RILI and the relationship to spirometry. MATERIAL AND METHODS: Eighty patients receiving radical radiotherapy for non-small cell lung cancer were prospectively assessed for dyspnea using two patient-completed tools: EORTC QLQ-LC13 dyspnea quality of life assessment and dyspnea visual analogue scale (VAS). Global quality of life, spirometry and radiation pneumonitis grade were also assessed. Comparisons were made with lung dose-volume parameters. RESULTS: The median survival of the cohort was 26 months. In the evaluable group of 59 patients there were positive correlations between lung dose-volume parameters and a change in dyspnea quality of life scale at 3 months (V30 p=0.017; V40 p=0.026; V50 p=0.049; mean lung dose p=0.05), and a change in dyspnea VAS at 6 months (V30 p=0.05; V40 p=0.026; V50 p=0.028) after radiotherapy. Lung dose-volume parameters predicted a 10% increase in dyspnea quality of life score at 3 months (V40; p=0.041, V50; p=0.037) and dyspnea VAS score at 6 months (V40; p=0.027) post-treatment. CONCLUSIONS: Worsening of dyspnea is an important symptom of RILI. We demonstrate a relationship between lung dose-volume parameters and a 10% worsening of subjective dyspnea scores. Our findings support the use of subjective dyspnea tools in future studies on radiation-induced lung toxicity, particularly at doses below conventional lung radiation tolerance limits.

The Prognostic Value of the Pretreatment Neutrophil/Lymphocyte Ratio in Patients with Glioblastoma Multiforme Brain Tumors: A Retrospective Cohort Study of Patients Treated with Combined Modality Surgery, Radiation Therapy, and Temozolomide Chemotherapy.

BACKGROUND: Recent studies have shown that the peripheral blood pretreatment neutrophil/lymphocyte ratio (NLR) is a prognostic measure in various cancers. The few studies evaluating NLR in glioblastoma multiforme (GBM) patients yielded inconsistent results. OBJECTIVES: The primary objective of our study was to test the ability of pretreatment NLR to predict the overall survival (OS) and progression-free survival (PFS) of patients with GBM treated by combined modality therapy (surgery, radiation, and temozolomide chemotherapy). A secondary objective was to evaluate the toxicity of the combined modality protocol in a consecutive series of patients treated in our center, in the context of a real-world universal health-care setting. METHODS: We analyzed 89 patients with GBM in a retrospective cohort analysis who were treated in Soroka University Medical Center's Oncology Department between the years 2005-2016. We analyzed NLR as a dichotomous variable at 3 cut-off points, 2.5, 3 and 4, as a predictor of OS and PFS. Methylation status of the O6-methylguanine-DNA methyltransferase (MGMT) promoter was not determined. RESULTS: No significant correlation was found between NLR and either OS or PFS. Factors that predicted a shorter OS were age and extent of surgery. Patients over 70 years of age had a statistically significant shorter OS, 12.5 months (95% CI: 10.4-14.5 months) versus 17.6 months (95% CI: 14.2-21.1 months) in those 70 years of age and younger (p = 0.004). The OS of patients undergoing partial resection (12.7 months 95% CI: 8.3-17.1 months) or biopsy only (9.3 months 95% CI: 7.8-24.6 months), was significantly shorter than that of patients undergoing total resection (18.9 months, 95% CI: 11.8-26.0 months; p = 0.035). There were no treatment-related deaths. The most common grade III-IV toxicities were thrombocytopenia, 12.4%, and fatigue, 13.5%. CONCLUSIONS: In our cohort of GBM patients treated with combined modality therapy, pretreatment NLR was not prognostic. Toxicity of treatment was acceptable. Investigation of the NLR with larger groups of patients selected by MGMT status is warranted.

Measurement of circulating cell-free DNA levels by a simple fluorescent test in patients with breast cancer.

OBJECTIVES: To evaluate circulating cell-free DNA (CFD) measured by a simple fluorescent assay as a biomarker of breast cancer. METHODS: We enrolled 38 patients with breast cancer before surgery, two patients with noncancerous breast lesions, nine patients after surgery, 16 healthy participants, and 29 control women admitted to the hospital emergency ward and released without hospitalization. CFD levels were measured by a direct fluorescence assay. RESULTS: Presurgery patients with cancer had elevated CFD levels (1,010 ± 642 ng/mL), which were higher than those measured in the healthy control group (395 ± 248 ng/mL, P < .001), the noncancer breast lesion group (386 ± 40 ng/mL), the nonhospitalized control group (492 ± 193 ng/mL, P < .001), and the postsurgery cancer group (398 ± 162 ng/mL, P < .01). The area under the receiver operating characteristic curve of the presurgery vs healthy patient group was 0.83. CFD levels correlated with tumor size (P = .03, ρ = 0.36), nodal involvement (P = .0003, ρ = 0.56), and TNM stage (P = .0002, ρ = 0.56). All patients with axillary node involvement had a CFD value greater than 600 ng/mL. CONCLUSIONS: CFD measured using a simple fluorometric assay has shown good correlation to stage and enhanced sensitivity to locally advanced disease. A large prospective study is warranted to evaluate if inclusion of this method as a decisive marker before mammography is advantageous.

Sodium valproate, a histone deacetylase inhibitor, enhances the efficacy of vinorelbine-cisplatin-based chemoradiation in non-small cell lung cancer cells.

AIM: To enhance the anticancer activity of vinorelbine, cisplatin and ionizing radiation (IR) combination against non-small cell lung cancer (NSCLC) cells by co-administration of sodium valproate (VPA), a histone deacetylase inhibitor, and to elucidate molecular events underpinning treatment efficacy. MATERIALS AND METHODS: The NSCLC A549 cell line was treated with cisplatin (0.2 µg/ml), vinorelbine (2 nM), VPA (1 mM) and IR (2.5 Gy) alone, or in combination. Cell proliferation, cell-cycle distribution, apoptosis, and levels of DNA double-strand breaks, activated DNA damage checkpoint kinases pCHK1, pCHK2, cell-cycle inhibitors p21CIP1/WAF1 and p27KIP1 were assessed. RESULTS: VPA markedly enhanced the DNA-damaging effect of the cisplatin-vinorelbine-IR combination and induced increased DSBs, and expression of pCHK2, pCHK1, p21CIP1/WAF1 and p27KIP1. These molecular changes led to cell-cycle arrest and increased apoptosis and consequently markedly curtailed cancer cell growth. CONCLUSION: VPA markedly enhances the anticancer activity of cisplatin-vinorelbine-IR combination. This finding has translational implications for enhancing the efficacy of anticancer treatment and for reducing side-effects by reducing doses of radiation and drugs.

Ethnic variation in toxicity and outcome of adjuvant chemoradiation for gastric cancer in Israel.

BACKGROUND: Data on differences in toxicity and efficacy of chemotherapy and radiotherapy among different ethnic groups is limited. We evaluated differences in toxicity, tolerability and clinical outcome of Ashkenazi and non-Ashkenazi Jews receiving postoperative chemoradiation for locally advanced gastric cancer (LAGC). PATIENTS AND METHODS: Between 6/2000-12/2007, 84 Ashkenazi patients and 60 non-Ashkenazi patients underwent chemoradiation following resection of LAGC (INT-116 trial). RESULTS: Patients' and tumor characteristics were comparable. Ashkenazi patients experienced significantly higher rates of fatigue, anorexia, and grade 3-4 dysphagia, as well as a trend for a higher rate of diarrhea. The incidence of other toxicities, dose adjustments of chemotherapy and radiotherapy and patient prognosis did not differ. CONCLUSION: This study shows higher rates of various toxicities among Ashkenazi patients receiving postoperative chemoradiation for LAGC compared to non-Ashkenazi patients. To our knowledge, this is the first study comparing treatment toxicity, tolerability and outcome between these two groups.

A study of inflammation-based predictors of tumor response to neoadjuvant chemoradiotherapy for locally advanced rectal cancer.

BACKGROUND: The ability of pretreatment laboratory markers of acute-phase inflammatory reactions like serum albumin level (SAL), hemoglobin (Hb), and absolute blood cell counts to predict complete pathological response (CPR) to neoadjuvant chemoradiotherapy (NACRT) in patients with locally advanced rectal cancer (LARC) has not yet been fully studied. METHODS: We retrospectively examined the relation between SAL, Hb and absolute blood cell counts, and CPR rates in 140 LARC patients treated with NACRT. RESULTS: Univariate analysis showed a significantly higher probability of CPR to NACRT in patients with clinical stage (CS) III LARC who had SAL >3.5 mg/dl (OR = 2.39; p = 0.04) and a neutrophil-to-lymphocyte ratio (NLR) value <5 (OR = 2.86; p = 0.03). The relation of CPR with SAL (OR = 2.11; p = 0.048) and NLR (OR = 2.54; p = 0.04) was confirmed by multivariate analysis in the same subset of patients. None of the parameters studied predicted CPR in patients with CS II disease. Patients who achieved CPR to NACRT had a higher probability of 5-year overall survival (HR 0.48; p = 0.01) and 5-year disease-free survival (HR 0.33; p = 0.003). CONCLUSIONS: Our data indicate that SAL >3.5 mg/dl and NLR <5 may be positively related to CPR after NACRT in patients with CS III LARC. Hypoalbuminemia and a high NLR may be considered an indication for a more aggressive approach to NACRT and postoperative adjuvant chemotherapy in this subset of patients. This hypothesis requires confirmation in a randomized study.

Low dose palliative radiotherapy for splenomegaly in hematologic disorders.

Splenomegaly (SM) is a common complication in hematologic disorders often associated with hypersplenism, and may cause pain, epigastric discomfort and variable systemic effects due to cytopenias. We retrospectively evaluated the results of palliative splenic irradiation (PSI) in terms of symptomatic relief in patients with hematologic disorders. In 1998-2006, 32 patients with hematologic disorders (median age 57) received 52 courses of PSI for SM. Twenty-one patients (66%) were diagnosed with myeloproliferative disorders (MPD), five patients (16%) had malignant lymphoma (ML), five patients (16%) had chronic lymphocytic leukemia (CLL) and one patient (3%) had hairy cell leukemia. Splenomegaly was accompanied by pain, anemia, thrombocytopenia and cachexia. Radiation therapy to the entire spleen was delivered by two parallel opposed fields using 0.5 Gy daily fractions given 5 days per week to a total dose of 6-10 Gy. PSI resulted in splenic size reduction in 78.8%, improvement of anemia in 75% and improvement of thrombocytopenia in 63.5% of PSI courses. The median survival (MS) of patients with MPD, CLL and ML was 45, 10 and 5 months, respectively. The MS of responders to PSI versus non-responders was 45 and 16 months, respectively (hazard ratio 0.17; p = 0.03; 95% confidence interval 0.035-0.84). In our hands, low dose PSI provided effective palliation for patients with hematologic disorders with SM. Splenic re-irradiation was feasible without excessive toxicity.

Postoperative chemoradiation for resected gastric cancer--is the Macdonald Regimen Tolerable? a retrospective multi-institutional study.

BACKGROUND: Postoperative chemoradiation as per Intergroup-0116 trial ("Macdonald regimen") is considered standard for completely resected high risk gastric cancer. However, many concerns remain with regards to the toxicity of this regimen. To evaluate the safety and tolerability of this regimen in a routine clinical practice setting, we analyzed our experience with its use. As we did not expect a different toxic profile in patients (pts) with positive margins (R1 resection), these were studied together with pts after complete resection (R0). PATIENTS AND METHODS: Postoperative chemoradiation therapy was given according to the original Intergroup-0116 regimen. Overall survival (OS) and disease free survival (DFS) rates were calculated using the Kaplan-Meier method. Comparison of OS and DFS between R0 and R1 pts was done using the log-rank test. RESULTS: Between 6/2000 and 12/2007, 166 pts after R0 (129 pts) or R1 (37 pts) resection of locally advanced gastric adenocarcinoma received postoperative chemoradiation; 61% were male and the median age was 63 years (range, 23-86); 78% had T ≥ 3 tumors and 81% had N+ disease; 87% of the pts completed radiotherapy and 54% completed the entire chemoradiation plan; 46.4% had grade ≥ 3 toxicity and 32% were hospitalized at least once for toxicity. Three pts (1.8%) died of toxicity: diarrhea (1), neutropenic sepsis (1) and neutropenic sepsis complicated by small bowel gangrene (1). The most common hematological toxicity was neutropenia, grade ≥ 3 in 30% of pts and complicated by fever in 15%. The most common non-hematological toxicities were nausea, vomiting and diarrhea. With a median follow-up of 51 months (range, 2-100), 62% of the R0 patients remain alive and 61% are free of disease. Median DFS and OS for R0 were not reached. R0 pts had a significantly higher 3-year DFS (60% vs. 29%, p = 0.001) and OS (61% vs. 33%, p = 0.01) compared with R1 pts. CONCLUSIONS: In our experience, postoperative chemoradiation as per Intergroup-0116 seems to be substantially toxic, with a mortality rate which seems higher than reported in that trial. Efficacy data appears comparable to the original report. Following postoperative chemoradiation, involvement of surgical margins still has a detrimental impact on patient outcome.

A combined pretreatment of 1,25-dihydroxyvitamin D3 and sodium valproate enhances the damaging effect of ionizing radiation on prostate cancer cells.

Radiotherapy is one of the curative treatment options for prostate cancer (PCa). However, effective doses of ionizing radiation (IR) have a high risk of side effects. To increase sensitivity of PCa to IR we pretreated human androgen-refractory DU145 PCa cells with a combination of sodium valproate (VPA), a well-tolerated drug with histone deacetylases inhibiting activity, and 1,25-dihydroxyvitamin D3, 1,25(OH)2D3, the active metabolite of vitamin D, a well known anticancer agent. The results show that irradiation (4Gy) of DU145 PCa cells pretreated with a combination of 1 mM VPA and 100 nM 1,25(OH)2D3 efficiently suppressed (87.9%) PCa cell proliferation. IR after combined pretreatment resulted in increased DNA double-strand breaks expressed as levels of phosphorylated histone H2A.X, compared with non-treated cells the increase was 58.1% in pretreated cells and 11.8% in non-pretreated cells (p<0.002). Combined pretreatment enhanced IR-induced activation of DNA damage checkpoint kinase Chk2, 39.0% in pretreated cells compared to 23.8% in non-pretreated cells (p<0.05). These molecular changes led to DNA replication blockade, S-phase cell-cycle arrest and enhanced apoptosis. Cumulatively, the results indicate that combined pretreatment with VPA and 1,25(OH)2D3 followed by IR is a highly effective treatment for human PCa cells. This observation may have important implications for reducing doses of radiation administered to cancer patients thus limiting the severity of side effects.

Effective avoidance of a functional spect-perfused lung using intensity modulated radiotherapy (IMRT) for non-small cell lung cancer (NSCLC): an update of a planning study.

IMRT and 3-dimensional conformal radiotherapy (3-DCRT) plans of 25 patients with non-small cell lung (NSCLC) were compared in terms of planning target volume (PTV) coverage and sparing of functional lung (FL) defined by a SPECT perfusion scan. IMRT resulted in significant reduction of functional V(20) and mean lung dose in stage III patients with inhomogeneous hypoperfusion. If the dose to FL is shown to be the determinant of lung toxicity, IMRT would allow for effective dose escalation by specific avoidance of functional lung.

A potential to reduce pulmonary toxicity: the use of perfusion SPECT with IMRT for functional lung avoidance in radiotherapy of non-small cell lung cancer.

BACKGROUND AND PURPOSE: The study aimed to examine specific avoidance of functional lung (FL) defined by a single photon emission computerized tomography (SPECT) lung perfusion scan, using intensity modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3-DCRT) in patients with non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Patients with NSCLC underwent planning computerized tomography (CT) and lung perfusion SPECT scan in the treatment position using fiducial markers to allow co-registration in the treatment planning system. Radiotherapy (RT) volumes were delineated on the CT scan. FL was defined using co-registered SPECT images. Two inverse coplanar RT plans were generated for each patient: 4-field 3-DCRT and 5-field step-and-shoot IMRT. 3-DCRT plans were created using automated AutoPlan optimisation software, and IMRT plans were generated employing Pinnacle(3) treatment planning system (Philips Radiation Oncology Systems). All plans were prescribed to 64 Gy in 32 fractions using data for the 6 MV beam from an Elekta linear accelerator. The objectives for both plans were to minimize the volume of FL irradiated to 20 Gy (fV(20)) and dose variation within the planning target volume (PTV). A spinal cord dose was constrained to 46 Gy. Volume of PTV receiving 90% of the prescribed dose (PTV(90)), fV(20), and functional mean lung dose (fMLD) were recorded. The PTV(90)/fV(20) ratio was used to account for variations in both measures, where a higher value represented a better plan. RESULTS: Thirty-four RT plans of 17 patients with stage I-IIIB NSCLC suitable for radical RT were analysed. In 6 patients with stage I-II disease there was no improvement in PTV(90), fV(20), PTV/fV(20) ratio and fMLD using IMRT compared to 3-DCRT. In 11 patients with stage IIIA-B disease, the PTV was equally well covered with IMRT and 3-DCRT plans, with IMRT producing better PTV(90)/fV(20) ratio (mean ratio - 7.2 vs. 5.3, respectively, p=0.001) and reduced fMLD figures compared to 3-DCRT (mean value - 11.5 vs. 14.3 Gy, p=0.001). This was due to reduction in fV(20) while maintaining PTV coverage. CONCLUSION: The use of IMRT compared to 3-DCRT improves the avoidance of FL defined by perfusion SPECT scan in selected patients with locally advanced NSCLC. If the dose to FL is shown to be the primary determinant of lung toxicity, IMRT would allow for effective dose escalation by specific avoidance of FL.

Prospective study of empiric monotherapy with ceftazidime for low-risk grade IV febrile neutropenia after cytotoxic chemotherapy in cancer patients.

PURPOSE: It was the aim of this study to evaluate the results of a prospective study in a single medical center using ceftazidime monotherapy in cancer patients with chemotherapy-induced grade IV febrile neutropenia and a low risk for gram-negative bacteremia. SUBJECTS AND METHODS: Thirty-eight patients were admitted with low-risk grade IV febrile neutropenia after chemotherapy for solid tumors. The median patient age was 57 years (range 18-74). Sixteen patients (42%) developed febrile neutropenia after the first cycle of current chemotherapy line, 9 patients (24%) received 2-3 cycles and 13 patients (34%) received more than 3 chemotherapy cycles before manifesting febrile neutropenia. Five patients were treated with prophylactic granulocyte colony-stimulating factor commenced 24 h after completion of the chemotherapy cycle. Empiric monotherapy with intravenous ceftazidime was started on admission and administered 2 g every 8 h. RESULTS: The mean polymorphic nuclear cell count on admission was 231 cells/mm(3). Ceftazidime therapy was well tolerated. Twenty-five (66%) patients responded with clinical improvement and complete resolution of fever within 48 h after initiation of ceftazidime therapy. Thirty-two (84%) patients were afebrile after 72 h of therapy. Thirty-three patients (87%) remained on unmodified ceftazidime therapy throughout their hospitalization. Five patients (13%) subsequently required modification of the treatment regimen for various reasons. Mean duration of fever and neutropenia were 2 (1-10) days and 4 (1-11) days, respectively. None of the patients discontinued therapy because of adverse effects. No positive blood cultures were obtained. No events of septic shock were observed. Mean duration of hospitalization was 6 days (range 3-12). CONCLUSION: In our series, monotherapy with intravenous ceftazidime appears safe and effective in cancer patients with low-risk grade IV febrile neutropenia after cytotoxic chemotherapy and may appreciably reduce antibiotics costs.

Comparison of forward planning with automated inverse planning for three-dimensional conformal radiotherapy of non-small cell lung cancer without IMRT.

The forward and inverse treatment plans of 10 patients with lung cancer were compared in terms of PTV coverage, sparing of normal lung and time required to generate a plan. The inverse planning produced as good treatment plans as an experienced dosimetrist with considerable reduction in staff time. When translated to other complex sites, inverse non-IMRT planning may have considerable impact on manpower requirements.