S.J. Feigenberg

Non-small cell lung cancer.

Most patients with non-small cell lung cancer (NSCLC) are diagnosed with advanced cancer. These guidelines only include information about stage IV NSCLC. Patients with widespread metastatic disease (stage IV) are candidates for systemic therapy, clinical trials, and/or palliative treatment. The goal is to identify patients with metastatic disease before initiating aggressive treatment, thus sparing these patients from unnecessary futile treatment. If metastatic disease is discovered during surgery, then extensive surgery is often aborted. Decisions about treatment should be based on multidisciplinary discussion.

Randomized Trial of Hypofractionated External-Beam Radiotherapy for Prostate Cancer

PURPOSE To determine if escalated radiation dose using hypofractionation significantly reduces biochemical and/or clinical disease failure (BCDF) in men treated primarily for prostate cancer. PATIENTS AND METHODS Between June 2002 and May 2006, men with favorable- to high-risk prostate cancer were randomly allocated to receive 76 Gy in 38 fractions at 2.0 Gy per fraction (conventional fractionation intensity-modulated radiation therapy [CIMRT]) versus 70.2 Gy in 26 fractions at 2.7 Gy per fraction (hypofractionated IMRT [HIMRT]); the latter was estimated to be equivalent to 84.4 Gy in 2.0 Gy fractions. High-risk patients received long-term androgen deprivation therapy (ADT), and some intermediate-risk patients received short-term ADT. The primary end point was the cumulative incidence of BCDF. Secondarily, toxicity was assessed. RESULTS There were 303 assessable patients with a median follow-up of 68.4 months. No significant differences were seen between the treatment arms in terms of the distribution of patients by clinicopathologic or treatment-related (ADT use and length) factors. The 5-year rates of BCDF were 21.4% (95% CI, 14.8% to 28.7%) for CIMRT and 23.3% (95% CI, 16.4% to 31.0%) for HIMRT (P = .745). There were no statistically significant differences in late toxicity between the arms; however, in subgroup analysis, patients with compromised urinary function before enrollment had significantly worse urinary function after HIMRT. CONCLUSION The hypofractionation regimen did not result in a significant reduction in BCDF; however, it is delivered in 2.5 fewer weeks. Men with compromised urinary function before treatment may not be ideal candidates for this approach.

Angiosarcoma after breast-conserving therapy

Angiosarcoma arising in the irradiated breast after breast‐conserving therapy is being reported with increasing frequency. As more women undergo breast‐conserving therapy, the incidence can be expected to increase. Surgeons, medical oncologists, and radiation oncologists will be faced with difficult management decisions for this aggressive disease.

Radiation therapy for giant cell tumors of bone.

For giant cell tumors of bone, does radiotherapy provide a safe and effective treatment? This retrospective review includes 24 patients with 26 histologically diagnosed tumors treated with megavoltage radiotherapy between March 1972 and July 1996. Of the 10 recurrent tumors, five had an intralesional resection, two had a biopsy, and three had no biopsy before radiotherapy. Of the 16 previously untreated tumors, one was irradiated after a marginal resection, five after an intracapsular resection, and 10 after biopsy alone. The total doses ranged from 35 to 55 Gy (median, 43 Gy) in fractions of 1.67 to 2.33 Gy per day. Twenty of 26 tumors (77%) were controlled locally. All of the local recurrences occurred within the irradiated field. Five of six patients with local recurrence were treated successfully with additional surgery. Salvage surgery after local recurrence required amputation of an extremity in three patients and a total knee replacement in one patient. The ultimate local control rate was 96% with one patient alive with progressive disease. Lung metastases in one patient were treated successfully with surgery, chemotherapy, and radiotherapy. In one patient a radiation-induced sarcoma developed 22 years after treatment. The authors conclude that radiation therapy is a safe and effective treatment option for benign giant cell tumors of bone. A total dose greater than 40 Gy is the only variable found to significantly influence local control.

Spatial-Temporal [18F]FDG-PET Features for Predicting Pathologic Response of Esophageal Cancer to Neoadjuvant Chemoradiation Therapy

PURPOSE To extract and study comprehensive spatial-temporal (18)F-labeled fluorodeoxyglucose ([(18)F]FDG) positron emission tomography (PET) features for the prediction of pathologic tumor response to neoadjuvant chemoradiation therapy (CRT) in esophageal cancer. METHODS AND MATERIALS Twenty patients with esophageal cancer were treated with trimodal therapy (CRT plus surgery) and underwent [(18)F]FDG-PET/CT scans both before (pre-CRT) and after (post-CRT) CRT. The 2 scans were rigidly registered. A tumor volume was semiautomatically delineated using a threshold standardized uptake value (SUV) of ≥2.5, followed by manual editing. Comprehensive features were extracted to characterize SUV intensity distribution, spatial patterns (texture), tumor geometry, and associated changes resulting from CRT. The usefulness of each feature in predicting pathologic tumor response to CRT was evaluated using the area under the receiver operating characteristic curve (AUC) value. RESULTS The best traditional response measure was decline in maximum SUV (SUVmax; AUC, 0.76). Two new intensity features, decline in mean SUV (SUVmean) and skewness, and 3 texture features (inertia, correlation, and cluster prominence) were found to be significant predictors with AUC values ≥0.76. According to these features, a tumor was more likely to be a responder when the SUVmean decline was larger, when there were relatively fewer voxels with higher SUV values pre-CRT, or when [(18)F]FDG uptake post-CRT was relatively homogeneous. All of the most accurate predictive features were extracted from the entire tumor rather than from the most active part of the tumor. For SUV intensity features and tumor size features, changes were more predictive than pre- or post-CRT assessment alone. CONCLUSION Spatial-temporal [(18)F]FDG-PET features were found to be useful predictors of pathologic tumor response to neoadjuvant CRT in esophageal cancer.

Megavoltage radiotherapy for aneurysmal bone cysts

PURPOSE An aneurysmal bone cyst (ABC) is a rapidly expansile and destructive benign tumor of bone that is usually treated by curettage and bone graft, with or without adjuvant treatment. For recurrent tumors, or tumors for which surgery would result in significant functional morbidity, does radiotherapy (RT) provide a safe and effective alternative for local control? PATIENTS AND METHODS Nine patients with histologically diagnosed aneurysmal bone cysts without other associated benign or malignant tumors were treated at the University of Florida with megavoltage RT between February 1964 and June 1992. The patients received local radiotherapy doses between 20 and 60 Gy, with 6 patients receiving 26--30 Gy. In 6 patients the diagnosis was made by biopsy alone; 3 underwent intralesional curettage before RT. Minimum follow-up was 20 months; 7 of 9 patients (77%) had follow-up greater than 11 years. RESULTS No patient experienced a local recurrence (median follow-up, 17 years). One patient required stabilization of the cervical spine 10 months after RT because of dorsal kyphosis from vertebral body collapse. No other significant side effects were experienced, and no patients developed secondary malignancies. Four patients were lost to follow-up: at 20 months, 11.5 years, 17 years, and 20 years after the initiation of treatment, none with any evidence of local recurrence. All of the patients who had significant pain before RT had relief of their symptoms within 2 weeks of completion of therapy. CONCLUSIONS Using modern-day RT, patients with recurrent or inoperable aneurysmal bone cysts can be treated effectively (with minimal toxicity) using a prescribed tumor dose of 26--30 Gy.

A COMPARISON OF ACUTE AND CHRONIC TOXICITY FOR MEN WITH LOW-RISK PROSTATE CANCER TREATED WITH INTENSITY-MODULATED RADIATION THERAPY OR 125I PERMANENT IMPLANT

PURPOSE To compare the toxicity and biochemical outcomes of intensity-modulated radiation therapy (IMRT) and (125)I transperineal permanent prostate seed implant ((125)I) for patients with low-risk prostate cancer. METHODS AND MATERIALS Between 1998 and 2004, a total of 374 low-risk patients (prostate-specific antigen < 10 ng/ml, T1c-T2b, Gleason score of 6 or less, and no neoadjuvant hormones) were treated at Fox Chase Cancer Center (216 IMRT and 158 (125)I patients). Median follow-up was 43 months for IMRT and 48 months for (125)I. The IMRT prescription dose ranged from 74-78 Gy, and (125)I prescription was 145 Gy. Acute and late gastrointestinal (GI) and genitourinary (GU) toxicity was recorded by using a modified Radiation Therapy Oncology Group scale. Freedom from biochemical failure was defined by using the Phoenix definition (prostate-specific antigen nadir + 2.0 ng/ml). RESULTS Patients treated by using IMRT were more likely to be older and have a higher baseline American Urological Association symptom index score, history of previous transurethral resection of the prostate, and larger prostate volumes. On multivariate analysis, IMRT was an independent predictor of lower acute and late Grade 2 or higher GU toxicity and late Grade 2 or higher GI toxicity. Three-year actuarial estimates of late Grade 2 or higher toxicity were 2.4% for GI and 3.5% for GU by using IMRT compared with 7.7% for GI and 19.2% for GU for (125)I, respectively. Four-year actuarial estimates of freedom from biochemical failure were 99.5% for IMRT and 93.5% for (125)I (p = 0.09). CONCLUSIONS The IMRT and (125)I produce similar outcomes, although IMRT appears to have less acute and late toxicity.

Angiosarcoma after breast-conserving therapy: experience with hyperfractionated radiotherapy

PURPOSE To report our promising results of hyperfractionated radiotherapy (RT) in conjunction with surgery for angiosarcoma occurring after breast-conserving therapy for early-stage breast cancer. METHODS AND MATERIALS Since 1997, 3 cases of angiosarcoma after breast-conserving therapy have been managed at the University of Florida. The histologic specimens in each case were reviewed and graded by one of us (J.D.R.). RESULTS Explosive growth of discolored skin lesions coincident with histologic evidence of angiosarcoma characterized all 3 cases but was preceded by a fairly indolent period (almost 2 years) of atypical vascular hyperplasia in 2 patients. All 3 patients were treated initially with radical surgery for the angiosarcoma, but extensive recurrences were noted within 1 to 2 months of surgery. Because of the extremely rapid growth noted before and after surgery, hyperfractionated RT was used. Two of the patients underwent planned resection after RT, and neither specimen demonstrated any evidence of high-grade angiosarcoma. All 3 patients were alive without any recurrent disease 22, 38, and 39 months after treatment. CONCLUSIONS Hyperfractionated irradiation appears to be effective treatment for rapidly proliferating angiosarcoma. For previously untreated angiosarcoma, we now recommend hyperfractionated RT followed by surgery to enhance disease control and remove as much reirradiated tissue as possible.

TOXICITY AND OUTCOME ANALYSIS OF PATIENTS WITH RECURRENT HEAD AND NECK CANCER TREATED WITH HYPERFRACTIONATED SPLIT-COURSE REIRRADIATION AND CONCURRENT CISPLATIN AND PACLITAXEL CHEMOTHERAPY FROM TWO PROSPECTIVE PHASE I AND II STUDIES

Patients with local recurrences or new head and neck primary tumors in previously irradiated tissues have few options for salvage treatment. One option for select patients is to undergo reirradiation with concurrent chemotherapy. The purpose of this study is to report the initial clinical results of the Fox Chase phase I and II prospective reirradiation and chemotherapy studies.

Impact of neck dissection on long-term feeding tube dependence in patients with head and neck cancer treated with primary radiation or chemoradiation.

The impact of posttreatment neck dissection on prolonged feeding tube dependence in patients with head and neck squamous cell cancer (HNSCC) treated with primary radiation or chemoradiation remains unknown.