Adaptive Radiation for Lung Cancer

The challenges of lung cancer radiotherapy are intra/inter-fraction tumor/organ anatomy/motion changes and the need to spare surrounding critical structures. Evolving radiotherapy technologies, such as four-dimensional (4D) image-based motion management, daily on-board imaging and adaptive radiotherapy based on volumetric images over the course of radiotherapy, have enabled us to deliver higher dose to target while minimizing normal tissue toxicities. The image-guided radiotherapy adapted to changes of motion and anatomy has made the radiotherapy more precise and allowed ablative dose delivered to the target using novel treatment approaches such as intensity-modulated radiation therapy, stereotactic body radiation therapy, and proton therapy in lung cancer, techniques used to be considered very sensitive to motion change. Future clinical trials using real time tracking and biological adaptive radiotherapy based on functional images are proposed

Exclusion of elective nodal irradiation is associated with minimal elective nodal failure in non-small cell lung cancer

<p>Abstract</p> <p>Background</p> <p>Controversy still exists regarding the long-term outcome of patients whose uninvolved lymph node stations are not prophylactically irradiated for non-small cell lung cancer (NSCLC) treated with definitive radiotherapy. To determine the frequency of elective nodal failure (ENF) and in-field failure (IFF), we examined a large cohort of patients with NSCLC staged with positron emission tomography (PET)/computed tomography (CT) and treated with 3-dimensional conformal radiotherapy (3D-CRT) that excluded uninvolved lymph node stations.</p> <p>Methods</p> <p>We retrospectively reviewed the records of 115 patients with non-small cell lung cancer treated at our institution with definitive radiation therapy with or without concurrent chemotherapy (CHT). All patients were treated with 3D-CRT, including nodal regions determined by CT or PET to be disease involved. Concurrent platinum-based CHT was administered for locally advanced disease. Patients were analyzed in follow-up for survival, local regional recurrence, and distant metastases (DM).</p> <p>Results</p> <p>The median follow-up time was 18 months (3 to 44 months) among all patients and 27 months (6 to 44 months) among survivors. The median overall survival, 2-year actuarial overall survival and disease-free survival were 19 months, 38%, and 28%, respectively. The majority of patients died from DM, the overall rate of which was 36%. Of the 31 patients with local regional failure, 26 (22.6%) had IFF, 5 (4.3%) had ENF and 2 (1.7%) had isolated ENF. For 88 patients with stage IIIA/B, the frequencies of IFF, any ENF, isolated ENF, and DM were 23 (26%), 3 (9%), 1 (1.1%) and 36 (40.9%), respectively. The comparable rates for the 22 patients with early stage node-negative disease (stage IA/IB) were 3 (13.6%), 1(4.5%), 0 (0%), and 5 (22.7%), respectively.</p> <p>Conclusion</p> <p>We observed only a 4.3% recurrence of any ENF and a 1.7% recurrence of isolated ENF in patients with NSCLC treated with definitive 3D-CRT without prophylactic irradiation of uninvolved lymph node stations. Thus, distant metastasis and IFF remain the primary causes of treatment failure and cancer death in such patients, suggesting little value of ENI in this cohort.</p

Determination of patient-specific internal gross tumor volumes for lung cancer using four-dimensional computed tomography

<p>Abstract</p> <p>Background</p> <p>To determine the optimal approach to delineating patient-specific internal gross target volumes (IGTV) from four-dimensional (4-D) computed tomography (CT) image data sets used in the planning of radiation treatment for lung cancers.</p> <p>Methods</p> <p>We analyzed 4D-CT image data sets of 27 consecutive patients with non-small-cell lung cancer (stage I: 17, stage III: 10). The IGTV, defined to be the envelope of respiratory motion of the gross tumor volume in each 4D-CT data set was delineated manually using four techniques: (<it>1</it>) combining the gross tumor volume (GTV) contours from ten respiratory phases (IGTV_AllPhases); (<it>2</it>) combining the GTV contours from two extreme respiratory phases (0% and 50%) (IGTV_2Phases); (<it>3</it>) defining the GTV contour using the maximum intensity projection (MIP) (IGTV_MIP); and (<it>4</it>) defining the GTV contour using the MIP with modification based on visual verification of contours in individual respiratory phase (IGTV_MIP-Modified). Using the IGTV_AllPhasesas the optimum IGTV, we compared volumes, matching indices, and extent of target missing using the IGTVs based on the other three approaches.</p> <p>Results</p> <p>The IGTV_MIPand IGTV_2Phaseswere significantly smaller than the IGTV_AllPhases(<it>p </it>< 0.006 for stage I and <it>p </it>< 0.002 for stage III). However, the values of the IGTV_MIP-Modifiedwere close to those determined from IGTV_AllPhases(<it>p </it>= 0.08). IGTV_MIP-Modifiedalso matched the best with IGTV_AllPhases.</p> <p>Conclusion</p> <p>IGTV_MIPand IGTV_2Phasesunderestimate IGTVs. IGTV_MIP-Modifiedis recommended to improve IGTV delineation in lung cancer.</p

Actinomyces associated with persistent vaginal granulation tissue.

BACKGROUND: We report a case of symptomatic actinomycosis associated with vaginal suture erosion and granulation tissue refractory to conservative management, in an outpatient setting. CASE: Three months after total vaginal hysterectomy and uterosacral ligament vaginal vault suspension, a woman complained of painless, intermittent vaginal discharge and spotting. Despite cauterization of granulation tissue, vaginal spotting persisted for another month. On re-examination, braided polyester suture that was found underlying the granulation tissue was removed. Recurrent symptoms, together with a biopsy revealing actinomycetes, prompted a trial of oral penicillin VK. With persistent symptoms and discomfort during attempts in the outpatient clinic, the woman eventually required suture removal in the operating room. Her symptoms subsequently resolved without recurrence, and no further antibiotic treatment was required. CONCLUSIONS: Actinomyces may be associated with persistent granulation tissue and vault suspension suture material. In rare circumstances, when tissue debridement and suture removal in the clinic is unsatisfactory, surgical intervention in the operating room may be necessary. Ten days of antibiotic therapy alone did not eradicate the granulation tissue, and symptoms resolved only after complete removal of the underlying permanent suture

Patterns of Cardiac Perfusion Abnormalities After Chemoradiotherapy in Patients with Lung Cancer

Objective:We evaluated the prevalence of myocardial perfusion defects using myocardial perfusion imaging (MPI) after chemoradiation or radiation therapy (CRT/RT) in lung cancer patients and described their patterns in relation to tumor location.Methods:MPI in 44 patients who received RT for lung cancer and 44 control patients were compared. The two groups were comparable in risk factors for coronary artery disease. Data regarding tumor stage and location, interval between CRT/RT and MPI, and mean radiation dose to the heart was collected. The level of radiation delivered to the affected segments of the left ventricle versus the normal segments was compared using the isodose lines on the simulation computed tomography.Results:Considering all tumor locations, 8 patients (18%) demonstrated MPI defects after CRT/RT versus 9 (20%) in the controls. However, 7 of 18 patients (39%) with centrally located tumors in the CRT/RT group versus only 1 of 15 patients (7%) in the control group demonstrated MPI defect (p= 0.04). The defects in the CRT/RT group were in the anterior and septal segments while the defects were in different segments in the controls. The median interval between end of RT and MPI was 12.3 months. The affected segments in the CRT/RT group received a mean radiation dose of 39.6 versus 11.4 Gy (p = 0.003) to the normal segments.Conclusions:CRT/RT to centrally located lung tumors tends to cause anterior/septal MPI defects. Abnormal MPI segments in the CRT/RT group have received significantly higher radiation than normal segments

Phase I Study of Celecoxib with Concurrent Irinotecan, Cisplatin, and Radiation Therapy for Patients with Unresectable Locally Advanced Non-Small Cell Lung Cancer

Purpose: Preclinical findings suggest that adding targeted therapies to combination radiation-chemotherapy can enhance treatment efficacy; however, this approach may enhance normal tissue toxicity. We investigated the maximum tolerated dose, dose-limiting toxicities, and response rate when the selective cyclooxygenase-2 inhibitor celecoxib is added to concurrent irinotecan, cisplatin, and radiation therapy for patients with inoperable stage II–III non-small cell lung cancer (NSCLC). Methods and Materials: Eighteen patients were analyzed in a phase I clinical dose-escalation trial. Celecoxib was given daily beginning 5 days before radiation followed by maintenance doses for 12 weeks. Toxicity was graded with the Common Terminology Criteria for Adverse Events V3.0 and response with the World Health Organization system. Primary endpoints were maximum tolerated dose of celecoxib and treatment toxicity; secondary endpoints were response and survival rates. Results: The maximum tolerated dose of celecoxib was not reached, in part owing to discontinuation of the drug supply. At doses of 200 or 400 mg/day, no patients experienced any dose-limiting toxicity (acute grade ≥4 esophagitis or pneumonitis, neutropenic fever or thrombocytopenia requiring transfusion, or acute grade ≥3 diarrhea). Grade 3 toxicities were leukopenia (five patients), fatigue (3), pneumonitis (2), dyspnea (1), pain (1), and esophageal stricture (1). Interestingly, pulmonary fibrosis (a late toxicity) was no more severe in the higher-dose (400-mg) group and may have been less common than in the lower-dose group. The clinical response rate was 100% (8 complete, 10 partial). Two-year rates were: overall survival 65%; local-regional control 69%; distant metastasis-free survival 71%; and disease-free survival 64%. Conclusion: Although preliminary, our results suggest that adding celecoxib to concurrent chemoradiation for inoperable NSCLC is safe and can improve outcome without increasing normal tissue toxicity

Orbital textures and charge density waves in transition metal dichalcogenides

Low-dimensional electron systems, as realized naturally in graphene or created artificially at the interfaces of heterostructures, exhibit a variety of fascinating quantum phenomena with great prospects for future applications. Once electrons are confined to low dimensions, they also tend to spontaneously break the symmetry of the underlying nuclear lattice by forming so-called density waves; a state of matter that currently attracts enormous attention because of its relation to various unconventional electronic properties. In this study we reveal a remarkable and surprising feature of charge density waves (CDWs), namely their intimate relation to orbital order. For the prototypical material 1T-TaS2 we not only show that the CDW within the two-dimensional TaS2-layers involves previously unidentified orbital textures of great complexity. We also demonstrate that two metastable stackings of the orbitally ordered layers allow to manipulate salient features of the electronic structure. Indeed, these orbital effects enable to switch the properties of 1T-TaS2 nanostructures from metallic to semiconducting with technologically pertinent gaps of the order of 200 meV. This new type of orbitronics is especially relevant for the ongoing development of novel, miniaturized and ultra-fast devices based on layered transition metal dichalcogenides