Phase I study and biomarker analysis of lapatinib and concurrent radiation for locally advanced breast cancer.

Purpose: This phase I study assessed the toxicity and safety of combining daily lapatinib with radiation therapy. Sequential tumor biopsies were obtained to evaluate changes in biomarkers, such as epidermal growth factor receptor (EGFR) and human EGFR-2 (HER2) signaling pathways.

Methods: Eligibility for this dose-escalation study included unresectable and locally recurrent or chemotherapy-refractory and locally advanced breast cancer, and adequate organ function.

The impact of local and regional disease extent on overall survival in patients with advanced stage IIIB/IV non-small cell lung carcinoma.

Purpose: Patients with advanced stage IIIB or stage IV non-small cell lung carcinoma are typically treated with initial platinum-based chemotherapy. A variety of factors (eg, performance status, gender, age, histology, weight loss, and smoking history) are generally accepted as predictors of overall survival. Because uncontrolled pulmonary disease constitutes a major cause of death in these patients, we hypothesized that clinical and radiographic factors related to intrathoracic disease at diagnosis may be prognostically significant in addition to conventional factors.

Challenges scoring radiation pneumonitis in patients irradiated for lung cancer.

Background And Purpose: To quantify uncertainties in scoring radiation pneumonitis.

Materials And Methods: Records of 434 patients irradiated for lung cancer from 2000 to 2010 were retrospectively reviewed; IRB-approved study. From these, 121 received ≥ 60 Gy for non-small cell lung cancer (NSCLC) with ≥ 6 months follow-up.

Predicting the need for palliative thoracic radiation after first-line chemotherapy for advanced nonsmall cell lung carcinoma.

Background: The objective of this secondary analysis was to identify patients with selected stage IIIB/IV nonsmall cell lung carcinoma and good performance status who were at high risk for requiring subsequent palliative thoracic radiotherapy after initial treatment with first-line chemotherapy.

Methods: The authors conducted a pooled analysis of patients at a single institution who enrolled onto 10 prospective phase 2 and 3 clinical trials that involved first-line, platinum-based chemotherapy. Baseline lung-related characteristics before trial enrollment were analyzed as possible prognostic factors for freedom from pulmonary events (defined either as subsequent thoracic radiation or as a new collapsed lung, which is an indication for thoracic radiation).

Radiosensitization of chemotherapy-refractory, locally advanced or locally recurrent breast cancer with trastuzumab: a phase II trial.

Purpose: Trastuzumab (Herceptin), an anti-human epidermal growth factor receptor 2 (HER2) antibody, has been shown to be an effective radiosensitizer in preclinical studies. The present Phase II trial evaluated trastuzumab plus radiotherapy in patients with HER2-positive, chemotherapy-refractory, locally advanced or locoregionally recurrent breast cancer.

Methods And Materials: Eligible patients had measurable disease, normal cardiac function, and biopsy-confirmed residual HER2-positive disease.

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.

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.

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.

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).

Post-chemotherapy gross tumor volume is predictive of survival in patients with stage III non-small cell lung cancer treated with combined modality therapy.

Purpose: To evaluate the influence of clinical covariates, particularly pre-chemotherapy gross tumor volume (GTV), post-chemotherapy GTV, on overall survival in the treatment of stage III non-small cell lung cancer (NSCLC).

Methods And Materials: We retrospectively analyzed 102 patients who were enrolled on three consecutive clinical trials, which employed the treatment paradigm of two cycles of induction chemotherapy followed by thoracic radiation therapy. The pre-chemotherapy GTV, post-chemotherapy GTV, change in GTV, histology, disease stage, performance status, age, race, treatment with concurrent chemoradiotherapy versus radiotherapy alone were evaluated to determine their impact on overall survival.

Comparison of three concomitant boost techniques for early-stage breast cancer.

Purpose: Whole breast radiotherapy (RT) followed by a tumor bed boost typically spans 5-6 weeks of treatment. Interest is growing in RT regimens, such as concomitant boost, that decrease overall treatment time, lessening the time/cost burden to patients and facilities.

Methods And Materials: Computed tomography (CT) scans from 20 cases were selected for this retrospective, dosimetric study to compare three different techniques of concomitant boost delivery: (1) standard tangents plus an electron boost, (2) intensity-modulated RT (IMRT) tangents using custom compensators plus an electron boost, and (3) IMRT tangents plus a conformal photon boost.

American Joint Committee on Cancer tumor-node-metastasis stage after neoadjuvant chemotherapy and breast cancer outcome.

Background: Response to neoadjuvant chemotherapy is used as an intermediate endpoint for breast cancer relapse and survival. Most breast cancer response classification systems use pathologic complete response, either alone or in conjunction with clinical assessments, to categorize response. We examined the ability of the revised 2003 American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging system, which considers both the number of involved axillary lymph nodes and the extent of tumor in the breast to predict patient survival after neoadjuvant chemotherapy for breast cancer.

Systematic review evaluating the timing of thoracic radiation therapy in combined modality therapy for limited-stage small-cell lung cancer.

Purpose: We employed meta-analytic techniques to evaluate early (E) versus late (L) timing of thoracic radiation therapy (RT) in limited-stage small-cell lung cancer (LS-SCLC). In addition, we assessed the impact of radiation fractionation and chemotherapeutic regimen on timing.

Methods: Randomized trials published after 1985 addressing timing of RT relative to chemotherapy in LS-SCLC were included.

Induction and concurrent chemotherapy with high-dose thoracic conformal radiation therapy in unresectable stage IIIA and IIIB non-small-cell lung cancer: a dose-escalation phase I trial.

Purpose: Local control rates at conventional radiotherapy doses (60 to 66 Gy) are poor in stage III non-small-cell lung cancer (NSCLC). Dose escalation using three-dimensional thoracic conformal radiation therapy (TCRT) is one strategy to improve local control and perhaps survival.

Patients And Methods: Stage III NSCLC patients with a good performance status (PS) were treated with induction chemotherapy (carboplatin area under the curve [AUC] 5, irinotecan 100 mg/m(2), and paclitaxel 175 mg/m(2) days 1 and 22) followed by concurrent chemotherapy (carboplatin AUC 2 and paclitaxel 45 mg/m(2) weekly for 7 to 8 weeks) beginning on day 43.

Seeking a home for a PET, part 2: Defining the appropriate place for positron emission tomography imaging in the staging of patients with suspected lung cancer.

In patients who have a high likelihood of having lung cancer, there is little role for positron emission tomography (PET) imaging for diagnosis of the primary lesion. The primary impact of PET imaging is in extrathoracic staging, but it should not replace a clinical evaluation by a physician experienced in lung cancer. PET imaging is most useful for confirmation of the presumed extrathoracic stage in patients with intermediate stages of lung cancer.

Seeking a home for a PET, part 1: Defining the appropriate place for positron emission tomography imaging in the diagnosis of pulmonary nodules or masses.

There is a growing experience with positron emission tomography (PET) in patients with pulmonary nodules or masses. As PET imaging becomes more widely available, it is important to thoughtfully define when application of this technology is warranted. Review of the literature to date suggests that PET imaging for diagnosis of pulmonary lesions is most useful in patients who have a low or intermediate risk of lung cancer as determined by an evaluation of symptoms, risk factors, and radiographic appearance.

High-dose conformal radiotherapy for treatment of stage IIIA/IIIB non-small-cell lung cancer: technical issues and results of a phase I/II trial.

Purpose: We completed a Phase I/II clinical trial (Lineberger Comprehensive Cancer Center 9603), in which we treated 62 Stage IIIA/IIIB inoperable non-small-cell lung cancer (NSCLC) patients with two cycles of induction carboplatin/paclitaxel chemotherapy, followed by concurrent weekly carboplatin/paclitaxel with radiation doses escalated from 60 to 74 Gy. The median survival of 24 months, 3-year survival rate of 38%, and the high dose of radiation used justified a critical analysis of the technical and clinical components of this trial.

Methods And Materials: Between 1996 and 1999, 62 sequential patients with inoperable Stage IIIA/IIIB NSCLC were enrolled and treated with two cycles of induction carboplatin (area under the concentration curve = 6 using the Calvert equation) and paclitaxel (225 mg/m(2)), followed by an escalating radiation dose of 60-74 Gy with concurrent carboplatin weekly (area under the concentration curve = 2) and paclitaxel weekly (45 mg/m(2)).