Judith Balogh

The impact of 18 FDG-PET on target and critical organs in CT-based treatment planning of patients with poorly defined non-small-cell lung carcinoma: a prospective study ☆

PURPOSE To prospectively study the impact of coregistering (18)F-fluoro-deoxy-2-glucose hybrid positron emission tomographic (FDG-PET) images with CT images on the planning target volume (PTV), target coverage, and critical organ dose in radiation therapy planning of non-small-cell lung carcinoma. METHODS AND MATERIALS Thirty patients with poorly defined tumors on CT, referred for radical radiation therapy, underwent both FDG-PET and CT simulation procedures on the same day, in radiation treatment position. Image sets were coregistered using external fiducial markers. Three radiation oncologists independently defined the gross tumor volumes, using first CT data alone and then coregistered CT and FDG-PET data. Standard margins were applied to each gross tumor volume to generate a PTV, and standardized treatment plans were designed and calculated for each PTV. Dose-volume histograms were used to evaluate the relative effect of FDG information on target coverage and on normal tissue dose. RESULTS In 7 of 30 (23%) cases, FDG-PET information changed management strategy from radical to palliative. In 5 of the remaining 23 (22%) cases, new FDG-avid nodes were found within 5 cm of the primary tumor and were included in the PTV. The PTV defined using coregistered CT and FDG-PET would have been poorly covered by the CT-based treatment plan in 17--29% of cases, depending on the physician, implying a geographic miss had only CT information been available. The effect of FDG-PET on target definition varied with the physician, leading to a reduction in PTV in 24-70% of cases and an increase in 30-76% of cases. The relative change in PTV ranged from 0.40 to 1.86. On average, FDG-PET information led to a reduction in spinal cord dose but not in total lung dose, although large differences in dose to the lung were seen for a few individuals. CONCLUSION The coregistration of planning CT and FDG-PET images made significant alterations to patient management and to the PTV. Ultimately, changes to the PTV resulted in changes to the radiation treatment plans for the majority of cases. Where possible, we would recommend that FDG-PET data be integrated into treatment planning of non-small-cell lung carcinoma, particularly for three-dimensional conformal techniques.

Clinical investigation: lungObserver variation in contouring gross tumor volume in patients with poorly defined non-small-cell lung tumors on CT: the impact of 18FDG-hybrid PET fusion☆

PURPOSE To quantify interobserver variation in gross tumor volume (GTV) localization using CT images for patients with non-small-cell lung carcinoma and poorly defined tumors on CT and to determine whether variability would be reduced if coregistered 2-[18F]fluoro-2-deoxy-d-glucose (FDG)-hybrid positron emission tomography (PET) with CT images were used. METHODS AND MATERIALS Prospectively, 30 patients with non-small-cell lung carcinoma had CT and FDG-hybrid PET examinations in radiation treatment position on the same day. Images were coregistered using eight fiducial markers. Guidelines were established for contouring GTVs. Three radiation oncologists performed localization independently. The coefficient of variation was used to assess interobserver variability. RESULTS The size of the GTV defined showed great variation among observers. The mean ratios of largest to smallest GTV were 2.31 and 1.56 for CT only and for CT/FDG coregistered data, respectively. The addition of PET reduced this ratio in 23 of 30 cases and increased it in 7. The mean coefficient of variation for GTV based on the combined modalities was significantly smaller (p < 0.01) than that for CT data only. CONCLUSIONS High observer variability in CT-based definition of the GTV can occur. A more consistent definition of the GTV can often be obtained if coregistered FDG-hybrid PET images are used.

Concurrent radiation and chemotherapy in vulvar carcinoma

Between June 1984 and February 1988 the role of radiation with concurrent infusional 5-fluorouracil with or without mitomycin C (CT-RT) was examined in 33 patients with vulvar cancer. The median duration of follow-up is 16 months (range 5 to 45 months). Nine received adjuvant postsurgical CT-RT and none has relapsed in the radiation field. Seven are alive disease free. Two have died of distant metastases. Of the 9 receiving definitive primary CT-RT, 6 had initial complete response with subsequent vulvar relapse developing in 3. Seven of the 9 remain disease free after CT-RT alone (in 3) or with the addition of a local excision of residual or recurrent disease (in 6). One patient did not respond to CT-RT and required a radical vulvectomy and groin node dissection. Fifteen received CT-RT for disease recurrence following primary surgery. Disease was present in the vulva only in 11, vulva and inguinal nodes in 1 and nodes only in 3. Eight of the 15 had a complete response and no relapses occurred in the treated sites. Four of the 8 dying of disease developed pulmonary metastases. Serious late complications developed in 2 patients, 1 avascular hip necrosis and 1 proctitis requiring a defunctioning colostomy. CT-RT appears tolerable and may contribute to enhanced locoregional control in recurrent or advanced disease. As initial therapy it may allow lesser surgery with preservation of normal anatomy in selected primary vulvar cancers.

ACCELERATED HYPOFRACTIONATION FOR EARLY-STAGE NON-SMALL- CELL LUNG CANCER

PURPOSE To describe the outcome of treating early-stage non-small-cell lung cancer (NSCLC) with an accelerated hypofractionated course of radiotherapy. METHODS AND MATERIALS A policy of treating early-stage NSCLC with a dose of 48 Gy in 12 once-daily fractions without elective irradiation of radiologically uninvolved regional nodes was adopted in 1996. We describe the outcome in 33 patients with NSCLC treated with this dose-fractionation schedule. RESULTS The median patient age was 72.0 years. Most patients (75.8%) were not surgical candidates because of medical comorbidities or old age. For staging, 97.0% underwent CT of the thorax, and mediastinoscopy was performed in 6.1%. All patients had Stage T1-T2N0, except for 4 patients with positive nodes based on pathologically involved or clinically enlarged lymph nodes adjacent to the primary tumor. The overall survival rate was 80.1% at 1 year and 46.0% at 2 years. The median survival was 22.6 months. The cause-specific survival rate was 89.8% at 1 year and 54.1% at 2 years. The recurrence-free survival rate was 66.4% at 1 year and 40.0% at 2 years. Lateral radiotherapy field margins of <2 cm predicted for inferior overall survival, cause-specific survival, and recurrence-free survival on univariate and multivariate analyses (p <0.05). The most commonly reported toxicities were acute dermatitis (30.3%) and late cutaneous/subcutaneous fibrosis (24.2%). CONCLUSION Accelerated hypofractionation for early-stage NSCLC appears to be safe and produces promising early results. Very small radiotherapy field margins may lead to an inferior outcome. Prospective studies are needed to determine the optimal dose-fractionation schedule.

Clinical considerations of Monte Carlo for electron radiotherapy treatment planning

Technical requirements for Monte Carlo based electron radiotherapy treatment planning are outlined. The targeted overall accuracy for estimate of the delivered dose is the least restrictive of 5% in dose, 5 mm in isodose position. A system based on EGS4 and capable of achieving this accuracy is described. Experience gained in system design and commissioning is summarized. The key obstacle to widespread clinical use of Monte Carlo is lack of clinically acceptable measurement based methodology for accurate commissioning.

Comparing treatment outcomes of radiotherapy and surgery in locally advanced carcinoma of the larynx: a comparison limited to patients eligible for surgery

PURPOSE The use of radical radiotherapy and surgery for salvage (RRSS) in locally advanced squamous cell carcinoma (SCC) of the larynx is controversial. In the absence of randomized studies, it is unclear if RRSS can match the rates of locoregional control and survival reported for primary surgery in this setting. The aim of this study was to compare treatment outcomes of radiotherapy and surgery in comparable patients with CS III-IV SCC of the larynx. METHODS AND MATERIALS Eighty-two patients with untreated T2N+M0 or T3T4NM0 SCC of the larynx were treated with a policy RRSS at the Toronto-Sunnybrook Regional Cancer Centre between June 1980 and December 1990. The medical records at presentation were reviewed independently by a panel of three surgical oncologists blinded as to treatment outcome to determine patient suitability for laryngectomy and neck dissection using eligibility criteria adopted by recent clinical trials. Treatment outcomes for surgery-eligible patients were compared to results of comparably staged patients in the surgical literature since 1980. RESULTS Sixty-three patients (77%) were eligible for study. With a median follow-up of 3 years, radiotherapy controlled the primary in 8/20 evaluable glottic primaries and 21/41 evaluable supraglottic primaries. Forty-five percent of patients surviving 5 years retained a functional larynx. Sixteen of 29 relapsing patients were salvaged with surgery. Disease above the clavicles was controlled in 65% of T3T4N0N+ glottic primaries (compared to a published range of 53% to 79%) and 82% of T3N0 glottic primaries (compared to a published range of 69% to 84%). The 5-year overall survival of patients with T3T4 glottic cancer was 54% compared to a published range of 50% to 63%. The cause-specific survival (CSS) of patients with T3N0 glottic primaries (86% at 1 year and 73% at 2 years) was identical to the only published report of CSS in the surgical literature. CONCLUSION A policy of RRSS offers a good chance of laryngeal conservation without compromising ultimate locoregional control or survival when compared to primary laryngectomy and neck dissection in patients with locally advanced carcinoma of the larynx meeting the surgical eligibility of clinical trials.

Patient preferences for oropharyngeal cancer treatment de-escalation.

The excellent prognosis of human papillomavirus (HPV)‐positive oropharyngeal squamous cell carcinomas (SCCs) against severe chemoradiotherapy (CRT) toxicities has opened discussion of deintensification trials. The purpose of this study was to describe the perspective of patients with HPV‐positive and HPV‐negative disease toward such studies.

EVALUATION OF MICROSCOPIC DISEASE IN ORAL TONGUE CANCER USING WHOLE-MOUNT HISTOPATHOLOGIC TECHNIQUES: IMPLICATIONS FOR THE MANAGEMENT OF HEAD-AND-NECK CANCERS

PURPOSE To map the distribution of microscopic disease (MD) in head-and-neck cancer by analyzing digital images of whole-mounted serial sections of tongue cancer specimens. METHODS AND MATERIALS Ten T1-3 oral tongue cancer specimens were evaluated. The specimens were sliced into 3-mm blocks from which one or more 4-μm slides were taken and digitized to create whole-mounted serial sections. Gross tumor and microscopic disease were digitally contoured on each slide. Lines perpendicular to the gross tumor volume (GTV) edge were created at 0.05-mm intervals and the distance between GTV and MD measured. RESULTS Of 88 slides assessed, 44 (50%) had evidence of MD. Of the 63,809 perpendicular lines drawn along the GTV edges, 2320 (3.6%) encountered microscopic disease along their path. The majority of MD abutted the GTV, and only 26.7% was noncontiguous with the GTV edge. The maximum distance from the border was 7.8 mm. Ninety-nine percent of all MD was within 4.75 mm and 95% was within 3.95 mm of the GTV. CONCLUSION In this study we were able to assess the distribution of MD more accurately than has been possible with routine pathologic techniques. The results indicate that when the GTV is correctly identified, there is very little MD to be found outside this volume. This has implications for the volume of tissue resected at surgery and the volume included in the clinical target volume in conformal radiotherapy planning.

Orbital Nonchromaffin Paraganglioma: A Case Report and Review of the Literature

Nonchromaffin paraganglioma (NCP), also called glomus body tumor or chemodectoma, is rarely found in the orbit. The behavior of orbital nonchromaffin paraganglioma may potentially be more aggressive than in other head and neck locations. Diagnosis depends on electron microscopic demonstration of membrane-bound neurosecretory granules. Results of histopathologic study show a well-circumscribed lesion without a true capsule with alveolar or organoid arrangements of epithelioid cells within a reticulin framework with thin-walled blood vessels. Cells are polygonal with round or oval nuclei containing rare mitotic figures and pale-staining cytoplasm. Differential diagnosis includes alveolar soft-part sarcoma, alveolar rhabdomyosarcoma, neuroblastoma, carcinoid, and granular cell tumor. Of 29 previously reported cases of orbital NCP, 16 have been reclassified as alveolar soft-part sarcoma. The authors report a patient with an electron microscopically established orbital NCP, with the history of a contralateral glomus jugulare tumor irradiated 14 years previously.

A Review of Radiotherapy for Merkel Cell Carcinoma of the Head and Neck

Merkel cell carcinoma of the head and neck (MCCHN) presents a clinical challenge due to its aggressive natural history, unpredictable lymphatic drainage, and high degree of treatment related morbidity. Histological examination of the regional lymph nodes is very important in determining the optimal treatment and is usually achieved by sentinel lymph node biopsy. Radiotherapy plays a critical role in the treatment of most patients with MCCHN. Surgery with adjuvant radiotherapy to the primary tumour site is associated with high local control rates. If lymph nodes are clinically or microscopically positive, adjuvant radiotherapy is indicated to decrease the risk of regional recurrence. The majority of locoregional recurrences occur at the edge or just outside of the radiation field, reflecting both the inherent radiosensitivity of MCC and the importance of relatively large volumes to include “in-transit” dermal lymphatic pathways. When surgical excision of the primary or nodal disease is not feasible, primary radiotherapy alone should be considered as a potentially curative modality and confers good loco-regional control. Concurrent chemoradiotherapy is well tolerated and may further improve outcomes.