Do refined consensus guidelines improve the uniformity of clinical target volume delineation for rectal cancer? Results of a national review project.

In a previous national central review project, 74% of the rectal cancer clinical target volumes (CTVs) needed a modification. In a follow-up initiative, we evaluated whether the use of refined international consensus guidelines improves the uniformity of CTV delineation in clinical practice.

Hypofractionated intensity modulated irradiation for localized prostate cancer, results from a phase I/II feasibility study.

BACKGROUND: To assess acute (primary endpoint) and late toxicity, quality of life (QOL), biochemical or clinical failure (secondary endpoints) of a hypofractionated IMRT schedule for prostate cancer (PC). METHODS: 38 men with localized PC received 66 Gy (2.64 Gy) to prostate,2 Gy to seminal vesicles (50 Gy total) using IMRT.Acute toxicity was evaluated weekly during radiotherapy (RT), at 1-3 months afterwards using RTOG acute scoring system. Late side effects were scored at 6, 9, 12, 16, 20, 24 and 36 months after RT using RTOG/EORTC criteria.Quality of life was assessed by EORTC-C30 questionnaire and PR25 prostate module. Biochemical failure was defined using ASTRO consensus and nadir+2 definition, clinical failure as local, regional or distant relapse. RESULTS: None experienced grade III-IV toxicity. 10% had no acute genito-urinary (GU) toxicity, 63% grade I; 26% grade II. Maximum acute gastrointestinal (GI) scores 0, I, II were 37%, 47% and 16%. Maximal acute toxicity was reached weeks 4-5 and resolved within 4 weeks after RT in 82%.Grade II rectal bleeding needing coagulation had a peak incidence of 18% at 16 months after RT but is 0% at 24-36 months. One developed a urethral stricture at 2 years (grade II late GU toxicity) successfully dilated until now. QOL urinary symptom scores reached a peak incidence 1 month after RT but normalized 6 months later. Bowel symptom scores before, at 1-6 months showed similar values but rose slowly 2-3 years after RT. Nadir of sexual symptom scores was reached 1-6 months after RT but improved 2-3 years later as well as physical, cognitive and role functional scales.Emotional, social functional scales were lowest before RT when diagnosis was given but improved later. Two years after RT global health status normalized. CONCLUSION: This hypofractionated IMRT schedule for PC using 25 fractions of 2.64 Gy did not result in severe acute side effects. Until now late urethral, rectal toxicities seemed acceptable as well as failure rates. Detailed analysis of QOL questionnaires resulted in the same conclusion.

Retropharyngeal nodes in squamous cell carcinoma of oropharynx: incidence, localization, and implications for target volume.

PURPOSE: To investigate the incidence and anatomic localization of retropharyngeal (RP) nodal involvement in patients with squamous cell carcinoma of the oropharynx. METHODS AND MATERIALS: The CT studies of 208 patients presenting with oropharyngeal carcinoma were retrospectively analyzed. The location of the nodal neck disease was registered according to recent consensus guidelines for target volume delineation, and special attention was given to the RP nodes. To obtain statistically significant predictors for RP nodal involvement, univariate and multivariate analyses were performed. RESULTS: RP adenopathies were present in 16% of all patients and in 23% of those patients with nodal disease in other neck sites. Ipsilateral involvement of Level II and contralateral involvement of Level III predicted for involvement of the ipsilateral RP nodes on multivariate analysis (p < 0.05). A solitary ipsilateral RP node was present in 3 (9%) of 34 patients with RP nodes; 2 of these 3 patients had a primary posterior pharyngeal wall tumor. No patients presented with a solitary contralateral RP node. CONCLUSION: Given the high incidence of RP nodal involvement in oropharyngeal cancer-16% of all patients and 23% of patients with pathologic nodal disease in other neck sites-RP nodes should be included in the target volume, especially in node-positive necks. In node-negative necks, inclusion of RP nodes into the target volume is advised in posterior pharyngeal wall tumors.

Prognostic influence of retropharyngeal lymph node metastasis in squamous cell carcinoma of the oropharynx.

PURPOSE: To investigate the impact of involvement of retropharyngeal lymph nodes on the prognosis of squamous cell carcinoma of the oropharynx. METHODS AND MATERIALS: The pretreatment computed tomographic scans of 208 patients with squamous cell carcinoma of the oropharynx were reviewed for the presence of metastatic retropharyngeal lymph nodes. All patients were treated at the Leuven department between 1984 and 2003: by radiotherapy alone in 84.1% of patients, by surgery with postoperative radiotherapy in 11.5%, and by concomitant chemoradiotherapy in 4.4%. Retropharyngeal node involvement was present in 34 (16%) patients. The influence on recurrence (local and regional), distant metastasis, and survival was retrospectively analyzed. Median follow-up was 47 months (3.9 years), and results were analyzed for 201 patients. RESULTS: At 5 years, patients with retropharyngeal adenopathy had significantly more regional recurrences (45% vs. 10%, p = 0.004). Involvement of retropharyngeal lymph nodes significantly (relative risk 4.29 [95% confidence interval 3.33-5.25], p = 0.01) and independently predicted regional recurrence in multivariate analysis. Disease-specific survival was significantly lower in the retropharyngeal node positive group (38% vs. 58%, p = 0.03). CONCLUSIONS: Retropharyngeal node involvement has a negative impact on the prognosis of squamous cell cancer of the oropharynx. Patients are particularly at risk for regional recurrence, resulting in worse disease-specific survival. Retropharyngeal node involvement should be taken into account in designing the treatment plan for these patients.

Dose-response relationships within the parotid gland after radiotherapy for head and neck cancer.

BACKGROUND AND PURPOSE: To determine the salivary function, after parotid-sparing radiotherapy (RT), of different regions within the parotid gland and to evaluate dose-function relationships within the parotid glands and between patients. PATIENTS AND METHODS: Sixteen head and neck cancer patients, irradiated between September 1999 and November 2000 using a conformal parotid-sparing technique, were included in this study. Before RT and 7 months after RT (range 6-10 months), a salivary gland scintigraphy was performed in all patients combined with a single photon emission computed tomography (SPECT). The salivary excretion fraction (SEF) was measured, after stimulation, in 8-12 transverse 5mm SPECT slices of each parotid. Loss of salivary excretion fraction (dSEF %) of these slices was calculated as the proportion of SEF after RT as compared to SEF before RT. Since the planning CT-scan and the SPECT-scintigraphy were performed in the same treatment position, the dose to a transverse slice within the parotid gland could be matched to the loss of salivary excretion fraction of that respective slice. A non-linear model was fitted to the dose-loss of function data and the dose resulting in 50% loss of salivary excretion fraction (D50) was calculated. RESULTS: Before RT, all but one patient presented with normal salivary excretion fractions (SEF) of both parotid glands. Within the same parotid gland, the SEF's of the different slices were almost equal. Seven months after RT, the reduction in SEF was statistically significant (P-value<0.0001). A significant difference in loss of salivary excretion fraction (dSEF) was also observed between both parotid glands (P<0.0001) as a result of the parotid-sparing technique. When plotting the dSEF of a slice versus the dose given to that slice, doses as low as 10-15 Gy could result in a serious loss of function (dSEF>50%). After fitting a non-linear model to these plots, the mean dose resulting in 50% loss of salivary excretion fraction (D50) 7 months after RT was 22.5 Gy. A large inter-patient variability was found in D50. CONCLUSIONS: Salivary SPECT is a useful tool for the evaluation of the salivary function of different slices within the parotid gland. Before irradiation, the different slices within one parotid gland act as functional sub-units contributing equally to the function of the entire gland. Seven months after an average dose of 22.5 Gy (D50) the functional sub-unit has lost 50% of its excretion fraction. The high inter-patient variability in D50 and the observation that low doses (10-15 Gy) can induce serious loss of function should prompt us in the clinic to reduce the dose to the parotids even lower than the threshold of 22.5 Gy.

Recurrences after conformal parotid-sparing radiotherapy for head and neck cancer.

BACKGROUND AND PURPOSE: Evaluation of loco-regional failure patterns and survival after parotid-sparing three-dimensional conformal and intensity modulated radiotherapy (IMRT) for head and neck cancer. PATIENTS AND METHODS: From June 1999 to July 2002, seventy-two patients with lateralised head and neck tumours, excluding nasopharyngeal tumours and patients with bilateral or contralateral neck disease, were irradiated with a parotid-sparing technique. Three-dimensional conformal planning was used in 68 patients, 4 patients were treated with dynamic IMRT. Bilateral neck node irradiation was performed in all patients, the junctional (or high level II) nodes, contralateral to the tumour, however, were excluded from the clinical target volume to spare the adjacent parotid from irradiation. In 20 patients with persistent or recurrent loco-regional disease, the localisation and volume of the treatment failure, as determined by computed tomography (CT), was copied on the pre-treatment CT-study used for treatment planning. Minimum, mean and maximum doses administered to the region of the failure were calculated and dose--volume histograms were computed of each failure. The failures were divided in three groups depending on the percentage of their volume receiving 95% of the prescribed dose. Recurrences were defined to be in-field (IF) if >95% of their volume received 95% of the prescribed dose and out-field (OF) if <20% of their volume received 95% of the prescribed dose. When 20-95% of the volume of the recurrence received 95% of the prescribed dose, this recurrence was defined as extending outside the field (EOF). RESULTS: With a median follow-up time of 19 months, the 2-year loco-regional control rate was 69% with primary radiotherapy and 63.5% with surgery followed by irradiation (P = 0.77). The 2-year overall survival rate for the entire patient population was 67.4%. At the time of analysis, 20 of the 72 patients had developed a loco-regional failure; 2 patients (2/20) presented with a loco-regional relapse combined with distant metastasis. Fifteen of the 20 loco-regional failures (15/20) occurred within the high dose region (IF). Five patients (5/20) developed a failure of which the bulky tumour mass was located within the high dose region but extending outside the treatment volume (EOF). No relapses were seen out-field (OF) and no patients relapsed in the spared junctional area contralateral to the tumour. CONCLUSIONS: The selection of patients treated with parotid-sparing radiotherapy, by omitting irradiation to the junctional nodes contralateral to the tumour, proved to be safe in our hands, since no recurrences developed in the spared area. As this parotid-sparing technique reduces significantly the dose to the contralateral parotid and is easy to perform, it should be considered for all selected patients.

Respiration-induced movement of the upper abdominal organs: a pitfall for the three-dimensional conformal radiation treatment of pancreatic cancer.

Respiration-induced movement of the upper abdominal organs (pancreas, liver and kidneys) was assessed in 12 subjects using dynamic magnetic resonance imaging. The movement of each organ in the cranio-caudal, the lateral and the anterior-posterior direction was deduced from the movement of the center of gravity on two-dimensional images. This center of gravity was computed from the volume delineated on sequential 8-mm slices of both sagittal and coronal dynamic series. The largest movements were noticed in the cranio-caudal direction for pancreas and liver (23.7+/-15.9 mm and 24.4+/-16.4 mm). The kidneys showed smaller movements in the cranio-caudal direction (left kidney 16.9+/-6.7 mm and right kidney 16.1+/-7.9 mm). The movements of the different organs in the anterior-posterior and lateral directions were less pronounced. It is of the greatest importance to be aware of these movements in the planning of a conformal radiation treatment for pancreatic cancer.