Cyril Danjoux

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.

Feasibility study : watchful waiting for localized low to intermediate grade prostate carcinoma with selective delayed intervention based on prostate specific antigen, histological and/or clinical progression

PURPOSE We assessed the feasibility of a watchful waiting protocol with selective delayed intervention using clinical, prostate specific antigen (PSA) or histological progression as treatment indications for clinically localized prostate cancer. MATERIALS AND METHODS In this prospective, single arm cohort study patients with favorable clinical parameters (stage T1b to T2b N0M0, Gleason score 7 or less and PSA 15 ng./ml. or less) are conservatively treated with watchful waiting. When a patient meets disease progression criteria, arbitrarily defined by the 3 parameters of the rate of PSA increase, clinical progression or histological upgrade on repeat prostate biopsy, appropriate treatment is implemented. Patients are followed every 3 months for the first 2 years and every 6 months thereafter. Serum PSA measurement and digital rectal examination are done at each visit and repeat prostate biopsy is performed 18 months after study enrollment. RESULTS Since November 1995, the study has accrued 206 patients with a median followup of 29 months (range 2 to 66). Of these men 137 remain on the surveillance protocol with no disease progression, while 69 were withdrawn from study for various reasons. There was clinical, PSA and histological progression in 16, 15 and 5 cases, respectively. The estimated actuarial probability of remaining on the surveillance protocol was 67% at 2 years and 48% at 4. The probability of remaining progression-free was 81% and 67% at 2 and 4 years, respectively. CONCLUSIONS A policy of watchful waiting with selectively delayed intervention based on predefined criteria of disease progression is feasible. This strategy offers the benefit of an individualized approach based on the demonstrated risk of clinical or biochemical progression with time and, thus, it may decrease the burden of therapy in patients with indolent disease, while providing definitive therapy for those with biologically active disease.

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.

PREVALENCE AND PATTERNS OF THE USE OF COMPLEMENTARY THERAPIES AMONG PROSTATE CANCER PATIENTS: AN EPIDEMIOLOGICAL ANALYSIS

PURPOSE We determine the prevalence and patterns of the use of complementary therapies among patients with and those at high risk for prostate cancer. MATERIALS AND METHODS A cross-sectional survey was performed of men presenting to 2 urban tertiary urology clinics for prostate cancer evaluation or followup, and those attending a prostate cancer support group. All men diagnosed with and those at high risk (positive family history or abnormal prostate specific antigen) for prostate cancer were eligible for study. A 9-item self-administered, anonymous questionnaire about complementary therapies was administered. RESULTS Of 357 patients who received the survey 155 from the urology clinics and 113 from the support group responded, for a total response rate of 75%. Of the patients presenting to urology clinics and the support group 27.4 and 38.9% with and 25.8 and 80% at high risk for prostate cancer, respectively, used some form of complementary therapy. The use significantly differed according to disease status (p = 0.001), and was highest among men who were clinically disease-free after radical therapy. Of the patients 24% did not inform the urologist of using alternative therapy. CONCLUSIONS The prevalence of the use of complementary therapy among patients with or at increased risk for prostate cancer was high and dependent on the disease state. Urologists should be aware of this pattern of use, and consider the potential effects when assessing patients for and with prostate cancer.

A randomized trial of radiation therapy compared to split course radiation therapy combined with mitomycin C and 5 fluorouracil as initial treatment for advanced laryngeal and hypopharyngeal squamous carcinoma

Two hundred and twelve patients with previously untreated advanced squamous carcinoma of the larynx or hypopharynx were randomized to receive initial treatment with radiotherapy, 50 Gy in 20 fractions in 28 days or split course radiotherapy and concurrent chemotherapy, 25 Gy in 10 fractions in 14 days followed by a 4 week rest and a further 25 Gy in 10 fractions in 14 days starting on day 43; Mitomycin C was given on day 1 and day 43 and 5FU continuous infusions on days 1--4 and days 43--46. Surgery was reserved for persistent or recurrent disease. Two hundred and nine of the 212 patients randomized were included in the analyses. Outcome analyses were performed at a median follow-up interval of 4.4 years. No patients were lost to follow-up. No significant difference was found between the two arms for the end points of local relapse-free rate (p = 0.91), regional relapse-free rate (p = 0.17, adjusted) or overall survival (p = 0.86). Eight-eight patients had attempted surgical resection following radiotherapy failure. The contribution of salvage surgery to overall survival was similar for both arms of the study as was the surgical complication rate. Serious late radiation toxicity was minimal (3% in the RT group, 0% in the radiation therapy plus chemotherapy group). The result of the trial shows no advantage in terms of local control or survival for the experimental treatment arm of split course radiotherapy and concurrent chemotherapy with Mitomycin C and 5 Fluorouracil compared to radiotherapy alone.

Palliation of bone metastases: a survey of patterns of practice among Canadian radiation oncologists☆

BACKGROUND Palliative radiotherapy constitutes nearly 50% of the workload in radiotherapy. Surveys on the patterns of practice in radiotherapy have been published from North America and Europe. Our objective was to determine the current pattern of practice of radiation oncologists in Canada for the palliation of bone metastases. METHOD A survey was sent to 300 practicing radiation oncologists in Canada. Five case scenarios were presented. The first three were patients with a single symptomatic site: breast cancer patient with pelvic metastasis, lung cancer male with metastasis to L3 and L1, respectively. The last two were breast and prostate cancer patients with multiple symptomatic bone metastases. RESULTS A total of 172 questionnaires were returned (57%) for a total of 860 responses. For the three cases with a single painful bone metastasis, over 98% would prescribe radiotherapy. The doses ranged from a single 8 to 30 Gy in ten fractions. Of the 172 respondents, 117 (68%) would use the same dose fractionation for all three cases, suggesting that they had a standard dose fractionation for palliative radiotherapy. The most common dose fractionation was 20 Gy in five fractions used by 84/117 (72%), and 8 Gy in one fraction by 19/117 (16%). In all five case scenarios, 81% would use a short course of radiotherapy (single 8 Gy, 17%; 20 Gy in five fractions, 64%), while 10% would prescribe 30 Gy in ten fractions. For the two cases with diffuse symptomatic bone metastases, half body irradiation (HBI) and radionuclides were recommended more frequently in prostate cancer than in breast cancer (46/172 vs. 4/172, P<0. 0001; and 93/172 vs. 10/172, P<0.0001, respectively). Strontium was the most commonly recommended radionuclide (98/103=95%). Since systemic radionuclides are not readily available in our health care system, 41/98 (42%) of radiation oncologists who would recommend strontium were not familiar with the dose. Bisphosphonates were recommended more frequently in breast cancer than in prostate cancer 13/172 (8%) vs. 1/172 (0.6%), P=0.001. CONCLUSION Local field external radiotherapy remains the mainstay of therapy, and the most common fractionation for bone metastases in Canada is 20 Gy in five fractions compared with 30 Gy in ten fractions in the US. Despite randomized trials showing similar results for single compared with fractionated radiotherapy, the majority of us still advocate five fractions. The frequency of employing a single fractionation has not changed since the last national survey in 1992. Nearly 70% use a standard dose fractionation to palliate localized painful metastasis by radiotherapy, independent of the site of involvement or tumor type. The pattern of practice of palliative radiotherapy for bone metastases in Canada is different to that reported previously from the US. The reasons why the results of randomized studies on bone metastases have no impact on the patterns of practice are worth exploring.

PSA doubling time of prostate carcinoma managed with watchful observation alone

PURPOSE To study prostate-specific antigen (PSA) doubling time of untreated, favorable grade, prostate carcinoma. METHODS AND MATERIALS A prospective single-arm cohort study has been in progress to assess the feasibility of a watchful observation protocol with selective delayed intervention using clinical, histologic, or PSA progression as treatment indication in untreated, localized, favorable grade prostate adenocarcinoma (T1b-T2bN0 M0, Gleason Score < or = 7, and PSA < or = 15 ng/mL). Patients are conservatively managed with watchful observation alone, as long as they do not meet the arbitrarily defined disease progression criteria. Patients are followed regularly and undergo blood tests including PSA at each visit. PSA doubling time (Td) is estimated from a linear regression of ln(PSA) on time, assuming a simple exponential growth model. RESULTS As of March 2000, 134 patients have been on the study for a minimum of 12 months (median, 24; range, 12-52) and have a median frequency of PSA measurement of 7 times (range, 3-15). Median age is 70 years. Median PSA at enrollment is 6.3 (range, 0.5-14.6). The distribution of Td is as follows: <2 years, 19 patients; 2-5 years, 46; 5-10 years, 25; 10-20 years, 11; 20-50 years, 6; > 50 years, 27. The median Td is 5.1 years. In 44 patients (33%), Td is greater than 10 years. There was no correlation between Td and patient age, clinical T stage, Gleason score, or initial PSA level. CONCLUSION Td of untreated prostate cancer varies widely. In our cohort, 33% have Td > 10 years. Td may be a useful tool to guide treatment intervention for patients managed conservatively with watchful observation alone.

A predictive model for survival in metastatic cancer patients attending an outpatient palliative radiotherapy clinic

PURPOSE To develop a predictive model for survival from the time of presentation in an outpatient palliative radiotherapy clinic. METHODS AND MATERIALS Sixteen factors were analyzed prospectively in 395 patients seen in a dedicated palliative radiotherapy clinic in a large tertiary cancer center using Coxs proportional hazards regression model. RESULTS Six prognostic factors had a statistically significant impact on survival, as follows: primary cancer site, site of metastases, Karnofsky performance score (KPS), and fatigue, appetite, and shortness of breath scores from the modified Edmonton Symptom Assessment Scale. Risk group stratification was performed (1) by assigning weights to the prognostic factors based on their levels of significance, and (2) by the number of risk factors present. The weighting method provided a Survival Prediction Score (SPS), ranging from 0 to 32. The survival probability at 3, 6, and 12 months was 83%, 70%, and 51%, respectively, for patients with SPS <or=13 (n = 133); 67%, 41%, and 20% for patients with SPS 14-19 (n = 129); and 36%, 18%, and 4% for patients with SPS >or=20 (n = 133) (p < 0.0001). Corresponding survival probabilities based on number of risk factors were as follows: 85%, 72%, and 52% (<or=3 risk factors)(n = 98); 68%, 47%, and 24% (4 risk factors)(n = 117); and 46%, 24%, and 11% (>or=5 factors)(n = 180)(p < 0.0001). CONCLUSION Clinical prognostic factors can be used to predict prognosis among patients attending a palliative radiotherapy clinic. If validated in an independent series of patients, the model can be used to guide clinical decisions, plan supportive services, and allocate resource use.

Determining the Incidence of Pain Flare Following Palliative Radiotherapy for Symptomatic Bone Metastases: Results From Three Canadian Cancer Centers

PURPOSE To determine the incidence of pain flare following radiotherapy (RT) for painful bone metastases. MATERIALS AND METHODS Patients with bone metastases treated with RT were eligible. Worst pain scores and analgesic consumption were collected before, daily during, and for 10 days after treatment. Pain flare was defined as a 2-point increase in the worst pain score (0-10) compared to baseline with no decrease in analgesic intake, or a 25% increase in analgesic intake with no decrease in worst pain score. Pain flare was distinguished from progression of pain by requiring the worst pain score and analgesic intake return to baseline levels after the increase/flare (within the 10-day follow-up period). RESULTS A total of 111 patients from three cancer centers were evaluable. There were 50 male and 61 female patients with a median age of 62 years (range, 40-89 years). The primary cancers were mainly breast, lung, and prostate. Most patients received a single 8 Gy (64%) or 20 Gy in five fractions (25%). The overall pain flare incidence was 44/111 (40%) during RT and within 10 days following the completion of RT. Patients treated with a single 8 Gy reported a pain flare incidence of 39% (27/70) and, with multiple fractions, 41% (17/41). CONCLUSION More than one third of the enrolled patients experienced a pain flare. Identifying at-risk individuals and managing potential pain flares is crucial to achieve an optimal level of care.

POSITIVE RESECTION MARGIN AND/OR PATHOLOGIC T3 ADENOCARCINOMA OF PROSTATE WITH UNDETECTABLE POSTOPERATIVE PROSTATE-SPECIFIC ANTIGEN AFTER RADICAL PROSTATECTOMY: TO IRRADIATE OR NOT?

PURPOSE To evaluate the efficacy of postoperative adjuvant radiotherapy (RT) for positive resection margin and/or pathologic T3 (pT3) adenocarcinoma of the prostate with undetectable postoperative prostate-specific antigen (PSA) levels. METHODS AND MATERIALS We retrospectively analyzed 125 patients with a positive resection margin and/or pT3 adenocarcinoma of the prostate who had undetectable postoperative serum PSA levels after radical prostatectomy. Seventy-three patients received postoperative adjuvant RT and 52 did not. Follow-up ranged from 1.5 to 12.0 years (median 4.2 for the irradiated group and 4.9 for the nonirradiated group). PSA outcome was available for all patients. Freedom from failure was defined as the maintenance of a serum PSA level of < or =0.2 ng/mL, as well as the absence of clinical local recurrence and distant metastasis. RESULTS No difference was found in the 5-year actuarial overall survival between the irradiated and nonirradiated group (94% vs. 95%). However, patients receiving adjuvant RT had a statistically superior 5-year actuarial relapse-free rate, including freedom from PSA failure, compared with those treated with surgery alone (88% vs. 65%, p = 0.0013). In the irradiated group, 8 patients had relapse with PSA failure alone. None had local or distant recurrence. In the nonirradiated group, 15, 1, and 2 had PSA failure, local recurrence, and distant metastasis, respectively. On Cox regression analysis, pre-radical prostatectomy PSA level and adjuvant RT were statistically significant predictive factors for relapse, and Gleason score, extracapsular invasion, and resection margin status were not. There was a suggestion that seminal vesicle invasion was associated with an increased risk of relapse. The morbidity of postoperative adjuvant RT was acceptable, with only 2 patients developing Radiation Therapy Oncology Group Grade 3 genitourinary complications. Adjuvant RT had a minimal adverse effect on urinary continence and did not cause serious gastrointestinal toxicity. CONCLUSION Postoperative adjuvant RT was associated with a lower risk of relapse, including freedom from PSA failure, compared with observation alone for pT3 and/or margin-positive disease with undetectable postoperative PSA levels. This was accomplished with a minimal risk of serious RT morbidity.