Michael P. Mac Manus

Positron Emission Tomography Is Superior to Computed Tomography Scanning for Response-Assessment After Radical Radiotherapy or Chemoradiotherapy in Patients With Non–Small-Cell Lung Cancer

PURPOSE To prospectively study the capacity of positron emission tomography (PET) and computed tomography (CT) to determine response soon after radical radiotherapy or chemoradiotherapy and, thereby, predict survival. PET is known to provide a more accurate estimate of true extent of disease than CT when used to stage non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS Seventy-three patients with NSCLC underwent [(18)F]fluorodeoxyglucose PET and CT scans before and after radical radiotherapy (n = 10) or chemoradiotherapy (n = 63). Follow-up PET scans were performed at a median of 70 days after radiotherapy. The median PET-CT interval was 1 day. Each patient had determinations of response to therapy made with PET and CT, categorized as complete response, partial response, no response, progressive disease, or nonassessable. Responses were correlated with subsequent survival. RESULTS Median survival after follow-up PET was 24 months. There was poor agreement between PET and CT responses (weighted kappa = 0.35), which were identical in only 40% of patients. There were significantly more complete responders on PET (n = 34) than CT (n = 10), whereas fewer patients were judged to be nonresponders (12 patients on PET v 20 on CT) or nonassessable (zero patients on PET v six on CT) by PET. Both CT and PET responses were individually significantly associated with survival duration; but on multifactor analysis that included the known prognostic factors of CT response, performance status, weight loss, and stage, only PET response was significantly associated with survival duration (P <.0001). CONCLUSION In NSCLC, a single, early, posttreatment PET scan is a better predictor of survival than CT response, stage, or pretreatment performance status.

Is radiotherapy curative for stage I and II low-grade follicular lymphoma? Results of a long-term follow-up study of patients treated at Stanford University.

PURPOSE To evaluate retrospectively the results of radiotherapy for 177 patients with stage I (n = 73 [41%]) and II (n = 104 [59%]) follicular small cleaved-cell and follicular mixed small cleaved-cell and large-cell non-Hodgkins lymphoma (NHL) treated in the Department of Radiation Oncology, Stanford University between 1961 and 1994. PATIENTS AND METHODS Histology was follicular small cleaved-cell in 101 (57%) cases and follicular mixed small cleaved-cell and large-cell in 76 (43%). Forty-five patients (25%) had staging laparotomy; 34 (19%) had extranodal involvement. All patients had received radiotherapy, either to one side of the diaphragm (involved or extended field) or to both sides (total lymphoid irradiation [TLI] or subtotal lymphoid irradiation [STLI]. Radiotherapy doses ranged from 35 to 50 Gy. RESULTS The median follow-up duration was 7.7 years. The longest follow-up duration was 31 years. Actuarial survival rates at 5, 10, 15, and 20 years were 82%, 64%, 44%, and 35%, respectively. The median survival time was 13.8 years. At 5, 10, 15, and 20 years, 55%, 44%, 40%, and 37% of patients, respectively, were relapse-free. Only five of 47 patients who reached 10 years without relapse subsequently developed recurrence. Survival and freedom from relapse (FFR) were significantly worse for older patients. Relapse rates were lower following treatment on both sides of the diaphragm or staging laparotomy. Univariate analysis showed that youth and staging laparotomy were associated with significantly better survival and that FFR was better following treatment on both sides of the diaphragm or laparotomy. CONCLUSION Radiotherapy remains the treatment of choice for early-stage low-grade follicular lymphomas. Patients who have remained free of disease for 10 years are unlikely to relapse.

F-18 fluorodeoxyglucose positron emission tomography staging in radical radiotherapy candidates with nonsmall cell lung carcinoma

Successful treatment of nonsmall cell lung carcinoma (NSCLC) with radical radiotherapy (RT) requires accurate delineation of tumor extent. Conventional computed tomography–based noninvasive staging often estimates intrathoracic thoracic tumor extent incorrectly and fails to detect distant metastasis. High sensitivity and specificity are reported for F‐18 fluorodeoxyglucose (FDG) positron emission tomography (PET) staging in potentially resectable NSCLC. The authors investigated FDG‐PET staging in radical RT candidates with unresectable NSCLC.

Should extrapulmonary small cell cancer be managed like small cell lung cancer

The aim of this study was to determine if extrapulmonary small cell carcinomas (EPSCC) should be managed using protocols similar to those for small cell lung cancer (SCLC).

Measurement of lung tumor volumes using three-dimensional computer planning software

PURPOSE To examine the interclinician variation in the definition of gross tumor volume (GTV) in patients undergoing radiotherapy for non-small-cell lung cancer (NSCLC), develop methods to minimize this variation, and test these methods. METHODS AND MATERIALS The radiotherapy planning computed tomography (CT) scans of 6 consecutive patients with NSCLC in which the radiologist was able to define and outline the GTV were used. Six oncologists independently contoured the tumors with the radiologists markings as a guide using a three-dimensional treatment planning system. Separate contours were prepared using only mediastinal window settings and using both mediastinal and lung window settings. The volumes were calculated using the planning system software (series 1). Factors that resulted in interclinician variation were determined, and, after a 3-year interval, 5 of the 6 clinicians redefined the GTVs using a revised protocol aimed at minimizing variation (series 2). RESULTS For series 1, the interclinician variation in the measurement of volumes ranged from 5%, in the most tightly measured tumor, to 42%, in the most variable, but was, on average, 20%. Statistically significant differences were noted among the clinicians (p = 0.002), that is, some clinicians tended to record relatively small and some relatively large volumes. The reasons for the variation among the oncologists included a tendency to include regions with a low probability of containing tumor, as if the oncologist were contouring a target volume; inclusion of adjacent atelectasis (ignoring the radiologists outline); and variable treatment of spicules. When the exercise was repeated using the revised protocol (series 2), the degree of interclinician variation was reduced, with a range of 7-22% (average 13%). In series 2, the differences among the clinicians were not statistically significant (p = 0.25). CONCLUSION Despite major radiologic input, significant variation occurred in the delineation of the three-dimensional GTVs of NSCLC among oncologists. Standardization of the approach with guidelines resulted in a reduction in this variation.

Early mortality after radical radiotherapy for non-small-cell lung cancer: comparison of PET-staged and conventionally staged cohorts treated at a large tertiary referral center

PURPOSE At our center, approximately 30% of radical radiotherapy (RRT) candidates become ineligible for RRT for non-small-cell lung cancer (NSCLC) after positron emission tomography (PET). We hypothesized that early cancer death rates would be lower in patients receiving RRT after PET staging compared with conventionally staged patients. METHODS AND MATERIALS Two prospective cohorts were compared. Cohort 1 consisted of all participants in an Australian randomized trial from our center given 60 Gy conventionally fractionated RRT with or without concurrent carboplatin from 1989 to 1995. Eligible patients had Stage I--III, Eastern Cooperative Oncology Group status 0 or 1, <10% weight loss, and had not undergone PET. Cohort 2 included all RRT candidates between November 1996 and April 1999 who received RRT after PET staging and fulfilled the above criteria for stage, Eastern Cooperative Oncology Group status, and weight loss. RESULTS Eighty and 77 eligible patients comprised the PET and non-PET groups, respectively. The PET-selected patients had significantly less weight loss; 73% and 49% of the PET and non-PET patients, respectively, received chemotherapy. The median survival was 31 months for PET patients and 16 months for non-PET patients. Mortality from NSCLC and other causes in the first year was 17% and 8% for PET patients and 32% and 4% for non-PET patients, respectively. The hazard ratio for NSCLC mortality for PET vs. non-PET patients was 0.49 (p = 0.0016) on unifactorial analysis and was 0.55 (p = 0.0075) after adjusting for chemotherapy, which significantly improved survival. CONCLUSION Patients selected for RRT after PET have lower early cancer mortality than those selected using conventional imaging.

Distribution of proliferating bone marrow in adult cancer patients determined using FLT-PET imaging.

PURPOSE Given that proliferating hematopoietic stem cells are especially radiosensitive, the bone marrow is a potential organ at risk, particularly with the use of concurrent chemotherapy and radiotherapy. Existing data on bone marrow distribution have been determined from the weight and visual appearance of the marrow in cadavers. 18F-fluoro-L-deoxythymidine concentrates in bone marrow, and we used its intensity on positron emission tomography imaging to quantify the location of the proliferating bone marrow. METHODS AND MATERIALS The 18F-fluoro-L-deoxythymidine positron emission/computed tomography scans performed at the Peter MacCallum Cancer Centre between 2006 and 2009 on adult cancer patients were analyzed. At a minimum, the scans included the mid-skull through the proximal femurs. A software program developed at our institution was used to calculate the percentage of administered activity in 11 separately defined bony regions. RESULTS The study population consisted of 13 patients, 6 of whom were men. Their median age was 61 years. Of the 13 patients, 9 had lung cancer, 2 had colon cancer, and 1 each had melanoma and leiomyosarcoma; 6 had received previous, but not recent, chemotherapy. The mean percentage of proliferating bone marrow by anatomic site was 2.9%±2.1% at the skull, 1.9%±1.2% at the proximal humeri, 2.9%±1.3% at the sternum, 8.8%±4.7% at the ribs and clavicles, 3.8%±0.9% at the scapulas, 4.3%±1.6% at the cervical spine, 19.9%±2.6% at the thoracic spine, 16.6%±2.2% at the lumbar spine, 9.2%±2.3% at the sacrum, 25.3%±4.9% at the pelvis, and 4.5%±2.5% at the proximal femurs. CONCLUSION Our modern estimates of bone marrow distribution in actual cancer patients using molecular imaging of the proliferating marrow provide updated data for optimizing normal tissue sparing during external beam radiotherapy planning.

Impact of 18F-Fluorodeoxyglucose Positron Emission Tomography Before and After Definitive Radiation Therapy in Patients With Apparently Solitary Plasmacytoma

PURPOSE To evaluate the impact of (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) on management of patients with apparently isolated plasmacytoma. METHODS AND MATERIALS Twenty-one patients with apparently solitary plasmacytoma who underwent FDG-PET for staging or restaging were identified from a central PET database. They were either candidates for or had received definitive radiation therapy (RT). RESULTS Seventeen patients had initial staging scans for bone (n = 11) or soft tissue (n = 6) plasmacytomas, and 11 had PET scans after RT. Only 1 of 14 known untreated sites of plasmacytoma was not identified on staging PET (lesion sensitivity = 93%). Three plasmacytomas were excised before PET. Staging PET influenced management in 6 of 17 patients (35%) by showing multiple myeloma (n = 1), discouraging RT after complete resection (n = 1), excluding plasmacytoma at a second site (n = 1), by increasing RT fields (n = 2), or by suggesting sarcoidosis (n = 1). Fifteen of 17 patients with initial staging PET scans received definitive RT. Restaging PET scans after RT showed complete metabolic response in 8 of 11 cases and progressive disease in 2. Two patients with either no response or partial metabolic response had late responses. Staging sestamibi and PET scans were concordant in five of six occasions (one sestamibi scan was false negative). CONCLUSIONS FDG-PET has value for staging and RT planning in plasmacytoma and potentially could have a role in response-assessment after RT. Slow resolution of FDG uptake posttreatment does not necessarily imply an adverse prognosis.

Effect of PET/CT on Management of Patients with Non–Small Cell Lung Cancer: Results of a Prospective Study with 5-Year Survival Data

We investigated the incremental management impact and prognostic value of staging with 18F-FDG PET/CT in patients with non–small cell lung cancer (NSCLC) being considered for potentially curative therapies. Methods: Information on 168 consecutive patients with NSCLC being considered for surgery or definitive radiotherapy with curative intent before PET/CT was entered into a prospective database. The pre-PET/CT management plan, based on conventional imaging (conventional CT, appropriately supplemented by bone scintigraphy or other modalities), was defined prospectively by referring clinicians before PET/CT results became available. After PET/CT, actual clinical management was recorded, and patients were followed up until 5 y or death. The appropriateness of PET/CT management plans was assessed by biopsy when available, clinical follow-up, and survival analysis. Results: Stage was discordant on PET/CT and conventional imaging in 50.6% of patients (41.1% upstaged, 9.5% downstaged), with high management impact (change in treatment modality or curative intent) in 42.3% of patients. Both conventional imaging stage and PET/CT stage were strongly predictive of overall survival (OS) but there were greater differences between hazard rates and separations in the OS curves for stage groupings determined using PET/CT. OS was also strongly predicted by PET/CT-directed choice of therapy (P < 0.0001). Conclusion: PET/CT frequently affects patient management and strongly predicts OS in NSCLC, supporting the appropriateness of such changes.

Association Between Pulmonary Uptake of Fluorodeoxyglucose Detected by Positron Emission Tomography Scanning After Radiation Therapy for Non–Small-Cell Lung Cancer and Radiation Pneumonitis

PURPOSE To study the relationship between fluorodeoxyglucose (FDG) uptake in pulmonary tissue after radical radiation therapy (RT) and the presence and severity of radiation pneumonitis. METHODS AND MATERIALS In 88 consecutive patients, (18)F-FDG-positron emission tomography was performed at a median of 70 days after completion of RT. Patients received 60 Gy in 30 fractions, and all but 15 had concurrent platinum-based chemotherapy. RT-induced pulmonary inflammatory changes occurring within the radiation treatment volume were scored, using a visual (0 to 3) radiotoxicity grading scale, by an observer blinded to the presence or absence of clinical radiation pneumonitis. Radiation pneumonitis was retrospectively graded using the Radiation Therapy Oncology Group (RTOG) scale by an observer blinded to the PET radiotoxicity score. RESULTS There was a significant association between the worst RTOG pneumonitis grade occurring at any time after RT and the positron emission tomograph (PET) radiotoxicity grade (one-sided p = 0.033). The worst RTOG pneumonitis grade occurring after the PET scan was also associated with the PET radiotoxicity grade (one-sided p = 0.035). For every one-level increase in the PET toxicity scale, the risk of a higher RTOG radiation pneumonitis score increased by approximately 40%. The PET radiotoxicity score showed no significant correlation with the duration of radiation pneumonitis. CONCLUSIONS The intensity of FDG uptake in pulmonary tissue after RT determined using a simple visual scoring system showed significant correlation with the presence and severity of radiation pneumonitis. (18)F-FDG-PET may be useful in the prediction, diagnosis and therapeutic monitoring of radiation pneumonitis.