Local Radiotherapy Intensification for Locally Advanced Non–small-cell Lung Cancer – A Call to Arms

Chemoradiotherapy, the standard of care for locally advanced non–small-cell lung cancer (NSCLC), often fails to eradicate all known disease. Despite advances in chemotherapeutic regimens, locally advanced NSCLC remains a difficult disease to treat, and locoregional failure remains common. Improved radiographic detection can identify patients at significant risk of locoregional failure after definitive treatment, and newer methods of escalating locoregional treatment may allow for improvements in locoregional control with acceptable toxicity. This review addresses critical issues in escalating local therapy, focusing on using serial positron emission tomography-computed tomography to select high-risk patients and employing stereotactic radiotherapy to intensify treatment. We further propose a clinical trial concept that incorporates the review's findings

Concomitant Radiotherapy and Chemotherapy for High-Risk Nonmelanoma Skin Carcinomas of the Head and Neck

Background. To report on the use and feasibility of a multimodality approach using concomitant radiotherapy and chemotherapy in patients with high-risk nonmelanoma skin carcinoma (NMSC) of the head and neck. Methods. Records of patients with NMSC of the head and neck who received concomitant CRT at the University of North Carolina between 2001 and 2007 were reviewed. Results. Fifteen identified patients had at least one of the following high-risk factors: T4 disease (93%), unresectability (60%), regional nodal involvement (40%), and/or recurrence (47%). Ten patients were treated in the definitive setting and five in the postoperative setting. Platinum based chemotherapy was given in 14 (93%) patients. Ten of fifteen (67%) patients completed all planned chemotherapy treatments, and thirteen patients (87%) completed at least 80% of planned chemotherapy. Mild radiation dermatitis occurred in all patients and reached grade 3 in 13% of patients. No patients experienced grade 4 or 5 toxicity. With a median followup of 31 months in surviving patients, the 2-year actuarial locoregional control and relapse-free survival were 79% and 49%, respectively. Conclusions. Definitive or postoperative chemoradiotherapy for patients with locally advanced or regionally metastasized NMSC of the head and neck appears feasible with acceptable toxicities and favorable locoregional control

Race, insurance type, and stage of presentation among lung cancer patients

The purpose of this study was to determine whether African-American lung cancer patients are diagnosed at a later stage than white patients, regardless of insurance type. The relationship between race and stage at diagnosis by insurance type was assessed using a Poisson regression model, with relative risk as the measure of association. The setting of the study was a large tertiary care cancer center located in the southeastern United States. Patients who were diagnosed with lung cancer between 2001 and 2010 were included in the study. A total of 717 (31%) African-American and 1,634 (69%) white lung cancer patients were treated at our facility during the study period. Adjusting for age, sex, and smoking-related histology, African-American patients were diagnosed at a statistically significant later stage (III/IV versus I/II) than whites for all insurance types, with the exception of Medicaid. Our results suggest that equivalent insurance coverage may not ensure equal presentation of stage between African-American and white lung cancer patients. Future research is needed to determine whether other factors such as treatment delays, suboptimal preventive care, inappropriate specialist referral, community segregation, and a lack of patient trust in health care providers may explain the continuing racial disparities observed in the current study

Acceptability and usage patterns of an image analysis workstation.

Critical to the successful deployment and use ofnew computer systems is the acceptance of the system by the users, i.e., the clinicians. We describe a study which evaluated, in an experimental setting, the potential acceptability of an image analysis workstation for radiation therapy. The acceptability and usage patterns were measured using semistructured questionnaires and maintaining logs of user interactions. The results ofthe study showed that the radiation oncologists, who were the subjects for the study, perceived the workstation as acceptable. The results also suggested several areas for improvement of workstation that could increase its acceptance in the clinical setting

Long-Term Follow-Up of a Phase I/II Trial of Dose Escalating Three-Dimensional Conformal Thoracic Radiation Therapy with Induction and Concurrent Carboplatin and Paclitaxel in Unresectable Stage IIIA/B Non-small Cell Lung Cancer

BACKGROUND: We conducted a modified phase I/II trial investigating the incorporation of three-dimensional conformal thoracic radiation therapy (TCRT) into the treatment paradigm of induction and concurrent carboplatin and paclitaxel in patients with unresectable stage IIIA/B non-small cell lung cancer. METHODS: Patients received 2 cycles of induction carboplatin (area under the curve of 6) and paclitaxel (225 mg/m) on days 1, and 22. On day 43 concurrent TCRT and weekly x6 of carboplatin (area under the curve = 2) and paclitaxel (45 mg/m) was initiated. The TCRT dose was escalated from 60 to 74 Gy in 4 cohorts (60, 66, 70, and 74 Gy), and the 74 Gy cohort was expanded into a phase II trial. RESULTS: Sixty-two patients were enrolled; the median age 57 years (range, 36-82), 39 were male (63%), 61 (98%) had a performance status of 0 or 1, 28 (45%) had stage IIIA disease, 21 (34%) had >5% weight loss, and the median forced expiratory volume 1 = 2.10 liters (range, 1.02-3.75). With a median follow-up for survivors of approximately 9 years (range, 7-11 years) the median progression-free survival, time to tumor progression, and overall survival (OS) (with 95% confidence intervals) were 10 (8.5-17), 15 (9-50), and 25 months (18-37), respectively. The 5-year progression-free survival and OS rates were 21% (12-32%) and 27% (17-39%), respectively. The 10-year OS rate was 14% (7-25%). CONCLUSION: The long term survival rate compares favorably to other treatment approaches for stage III non-small cell lung cancer

Challenges scoring radiation pneumonitis in patients irradiated for lung cancer

To quantify uncertainties in scoring radiation pneumonitis

Induction Chemotherapy with Carboplatin, Irinotecan, and Paclitaxel Followed by High Dose Three-Dimension Conformal Thoracic Radiotherapy (74 Gy) with Concurrent Carboplatin, Paclitaxel, and Gefitinib in Unresectable Stage IIIA and Stage IIIB Non-small Cell Lung Cancer

Combined modality therapy is a standard therapy for patients with unresectable stage III non-small cell lung cancer (NSCLC). Gefitinib is active in advanced NSCLC, and in preclinical models, it potentiates the activity of radiation therapy. We investigate the tolerability of gefitinib in combined modality therapy in combination with three-dimensional thoracic conformal radiation therapy (3-dimensional TCRT).Stage III patients with a good performance status were treated with induction chemotherapy (carboplatin area under the curve [AUC] of 5, irinotecan 100 mg/m2, and paclitaxel 175 mg/m2 days 1 and 22) with pegfilgrastim support followed by concurrent chemotherapy (carboplatin AUC 2, and paclitaxel 45 mg/m2 weekly) and gefitinib 250 mg daily beginning on day 43 with 3-dimensional TCRT to 74 Gy.Between March 2004 and January 2006, 23 patients received treatment on the trial: median age 62 years (range 44–82), 52% female, 61% stage IIIA, 61% performance status 0, 17% ≥5% weight loss, and 91% underwent positron emission tomography staging. Induction chemotherapy with pegfilgrastim support was well tolerated and active (partial response rate, 24%; stable disease, 76%; and early progression, 0%). Twenty-one patients initiated the concurrent chemoradiation, and 20 patients completed therapy to 74 Gy. The primary toxicities of concurrent chemoradiation were grade 3 esophagitis (19.5%) and cardiac arrhythmia (atrial fibrillation) (9.5%). The median progression-free survival and overall survival were 9 months (95% confidence intervals [CI]: 7–13 months) and 16 months (95% CI: 10–20 months), respectively.Treatment with induction chemotherapy and gefitinib concurrent with 3-dimensional TCRT has an acceptable toxicity and tolerability, but the survival results were disappointing

Late Complications of High-Dose (≥66 Gy) Thoracic Conformal Radiation Therapy in Combined Modality Trials in Unresectable Stage III Non-small Cell Lung Cancer

BACKGROUND: Combined modality treatment is the standard of care for patients (pts) with unresectable stage III non-small cell lung cancer. Dose escalation of radiotherapy is one strategy used to improve locoregional control and survival, but it increases the risk of both early and late treatment related toxicities. METHODS: From May 1996 to August 2004, a total of 112 stage III non-small cell lung cancer pts were treated on 4 phase I/II or phase II trials to assess the safety and feasibility of high-dose (60-90 Gy) thoracic conformal radiotherapy. Patients who received >/=66 Gy (n = 88) were included in an analysis of late complications. Late complications were defined as complications that developed or persisted >/=90 days postradiotherapy. The classic lung toxicities of radiation pneumonitis and fibrosis were not included in this analysis. RESULTS: Of the 88 patients included in this analysis of late complications, 21 patients (24%) developed a late complication and a total of 28 late complications were observed. The late complications were: pulmonary (n = 5; bronchial stenosis [n = 3] and fatal pulmonary hemoptysis [n = 2]), esophageal (n = 6), cardiac (n = 9), osseous (n = 6), and second primary tumor (n = 2). The median survival for all patients enrolled on the 4 trials (with 95% confidence interval [CI]) was 24.7 months (18.1-30.4 months), and the 5-year overall survival (with 95% CI) was 24% (16-32%). Data to assess for radiographic evidence of local progression were available for 99 patients, and the rate of local progression was 43% (95% CI 34-53%). CONCLUSIONS: High-dose thoracic conformal radiotherapy is feasible and results in promising survival outcomes. Late complications occur in a minority of patients

Induction Chemotherapy with Carboplatin, Irinotecan, and Paclitaxel Followed by High Dose Three-Dimension Conformal Thoracic Radiotherapy (74 Gy) with Concurrent Carboplatin, Paclitaxel, and Gefitinib in Unresectable Stage IIIA and Stage IIIB Non-small Ce

Introduction: Combined modality therapy is a standard therapy for patients with unresectable stage III non-small cell lung cancer (NSCLC). Gefitinib is active in advanced NSCLC, and in preclinical models, it potentiates the activity of radiation therapy. We investigate the tolerability of gefitinib in combined modality therapy in combination with three-dimensional thoracic conformal radiation therapy (3-dimensional TCRT). Methods: Stage III patients with a good performance status were treated with induction chemotherapy (carboplatin area under the curve [AUC] of 5, irinotecan 100 mg/m 2 , and paclitaxel 175 mg/

Psychiatric diagnoses are not mental process: Wittgenstein on conceptual confusion

Background: Empirical explanation and treatment repeatedly fail for psychiatric diagnoses. Diagnosis is mired in conceptual confusion that is illuminated by Ludwig Wittgensteins later critique of philosophy (Philosophical Investigations). This paper examines conceptual confusions in the foundation of psychiatric diagnosis from some of Wittgensteins important critical viewpoints. Argument: Diagnostic terms are words whose meanings are given by usages not definitions. Diagnoses, by Wittgensteins analogy with games, have various and evolving usages that are connected by family relationships, and no essence or core phenomenon connects them. Their usages will change according to the demands and contexts in which they are employed. Diagnoses, like many psychological terms, such as reading or understanding, are concepts that refer not to fixed behavioural or mental states but to complex apprehensions of the relationship of a variety of behavioural phenomena with the world. A diagnosis is a sort of concept that cannot be located in or explained by a mental process. Conclusion: A diagnosis is an exercise in language and its usage changes according to the context and the needs it addresses. Diagnoses have important uses but they are irreducibly heterogeneous and cannot be identified with or connected to particular mental processes or even with a unity of phenomena that can be addressed empirically. This makes understandable not only the repeated failure of empirical science to replicate or illuminate genetic, neurophysiologic, psychic or social processes underlying diagnoses but also the emptiness of a succession of explanatory theories and treatment effects that cannot be repeated or stubbornly regress to the mean. Attempts to fix the meanings of diagnoses to allow empirical explanation will and should fail as there is no foundation on which a fixed meaning can be built and it can only be done at the cost of the relevance and usefulness of diagnosis