Unilateral radiotherapy for tonsil cancer: Potential dose distribution optimization with a simple two-field intensity-modulated radiation therapy beam arrangement

Background and purpose

To evaluate the feasibility and dosimetric optimization potential of a unilateral two-field intensity-modulated radiotherapy (IMRT) technique in the curative treatment of lateralized tonsil cancer.

Materials and methods

Six patients with lateralized tonsillar carcinoma were treated unilaterally with a two-field IMRT technique (oblique-anterior and oblique-posterior fields, with or without collimator and couch rotation). Alternative IMRT plans using seven non-opposed coplanar fields were compared with the two-field plans for each patient.

Results

Planning target volume (PTV) coverage was excellent with the two-field technique, using a relatively low number of monitor units (MU) (median, 441; range, 309-550). Dose constraints were respected for all organs at risk (OAR). Mean doses to contralateral parotid and submandibular glands were 3.9 and 17.7 Gy, respectively. Seven-field IMRT provided similar PTV coverage, with statistically significant better dose homogeneity and conformality. However, the mean delivered dose to the contralateral parotid (3.9 vs. 9.0 Gy, p = 0.001) as well as the mean number of MU (437 vs. 814, p = 0.002) and consequently machine time were lower with two-field IMRT.

Conclusions

Unilateral two-field IMRT is a simple and feasible technique providing excellent tumor coverage and optimal OAR sparing while reducing the number of MU and treatment time.     

Secondary radiation doses of intensity-modulated radiotherapy and proton beam therapy in patients with lung and liver cancer

Purpose

To compare the secondary radiation doses following intensity-modulated radiotherapy (IMRT) and proton beam therapy (PBT) in patients with lung and liver cancer.

Methods and materials

IMRT and PBT were planned for three lung cancer and three liver cancer patients. The treatment beams were delivered to phantoms and the corresponding secondary doses during irradiation were measured at various points 20-50 cm from the beam isocenter using ion chamber and CR-39 detectors for IMRT and PBT, respectively.

Results

The secondary dose per Gy (i.e., a treatment dose of 1 Gy) from PBT for lung and liver cancer, measured 20-50 cm from the isocenter, ranged from 0.17 to 0.086 mGy. The secondary dose per Gy from IMRT, however, ranged between 5.8 and 1.0 mGy, indicating that PBT is associated with a smaller dose of secondary radiation than IMRT. The internal neutron dose per Gy from PBT for lung and liver cancer, 20-50 cm from the isocenter, ranged from 0.03 to 0.008 mGy.

Conclusions

The secondary dose from PBT is less than or compatible to the secondary dose from conventional IMRT. The internal neutron dose generated by the interaction between protons and body material is generally much less than the external neutron dose from the treatment head.     

Time course of hypothalamic-pituitary deficiency in adults receiving cranial radiotherapy for primary extrasellar brain tumors

Background

No longitudinal data on hypothalamic-pituitary (HP) function are available in patients who had received cranial radiation therapy (CRT) for primary extrasellar brain tumors (PBT).

Purpose

To investigate the effects of CRT on HP function in adults with PBT.

Patients and methods

Twenty-six adults irradiated for PBT and six CRT naive controls were studied. CRT was delivered with 6 MV X-ray by a linear accelerator (2 Gy fraction schedule). Gross Tumor Volume (GTV) excluded the HP region that was contoured on the planning CT. Median dose to the HP region was 41.8 Gy (IQR: 30.7-49.8).

Results

All controls maintained normal HP function. Hypopituitarism developed in 38% of CRT patients (GH deficiency 29%, ACTH 22%, TSH 14%, gonadotropin 4%, no abnormal prolactin level or diabetes insipidus). All HP failures occurred within 32 months after CRT.

Conclusions

Adults undergoing CRT for PBT are at increased risk for HP dysfunction within 3 years from CRT. Endocrine surveillance is recommended also in adults patients exposed to CRT for primary brain tumors distant from HP region.     

Intensity modulated radiotherapy in the management of sacral chordoma in primary versus recurrent disease

Purpose

To investigate treatment outcome in patients suffering from sacral chordoma after intensity modulated radiotherapy (IMRT) for primary versus recurrent disease.

Material/methods

We report on 34 patients with histologically proven sacral chordoma. Seventeen patients were treated at time of initial diagnosis with post-operative IMRT (n = 13) or with IMRT alone (n = 4). Seventeen patients were treated in recurrent disease after surgery (n = 11) or with radiotherapy alone (n = 6). Median total dose to the boost volume (PTV2) was 66 Gy (range, 72-54) with 2 Gy per fraction using an integrated boost concept. Median dose to target volume (PTV1) was 54 Gy in 1.8 Gy.

Results

Local control was 35% (12/34) and overall survival 74% (25/34) after a median follow-up of 4.5 years. Actuarial local control was 79%, 55% and 27% after 1, 2 and 5 years, respectively. Local control was significantly higher in patients treated for primary tumors (p < 0.03) and in total doses >60 Gy (p < 0.01). Actuarial overall survival was 97%, 91% and 70% after 1, 2 and 5 years, respectively.

Conclusion

These data demonstrate that local control after IMRT is higher in patients treated for primary tumors and using higher radiation doses. Therefore, we recommend radiotherapy as part of initial treatment in sacral chordoma.     

IMRT or conformal radiotherapy for adjuvant treatment of retroperitoneal sarcoma?

Purpose

To compare the dose distribution between three-dimensional conformal radiotherapy (3DCRT), intensity modulated radiotherapy (IMRT) with six coplanar beams (6b-IMRT) and IMRT with nine coplanar beams (9b-IMRT) during adjuvant radiotherapy for retroperitoneal sarcoma.

Methods and materials

The 10 most recent patients who had received adjuvant radiotherapy were reviewed. Three different treatment plans were generated (3DCRT, 6b-IMRT and 9b-IMRT) to deliver 50.4 Gy in 28 fractions. The dose delivered to the organs at risk (intestinal cavity (IC), contra- and ipsilateral kidney, liver, stomach and whole body), and the conformity index (CI) were compared.

Results

The integral dose to the intestinal cavity was similar with the three modalities but the dose distribution was different, with a change-over around 25 Gy: the V50 and the V40 were reduced five- and twofold, respectively, with IMRT compared to 3DCRT, and the V20 was increased by about 25% with IMRT.A similar integral dose was delivered to the whole body with the three modalities. The treated volume (V95 body) was approximately halved with IMRT compared to 3DCRT, and the CI was twice as good with IMRT than with 3DCRT. As expected, the V5 (body) was higher with IMRT compared to 3DCRT (p < 0.0001) (a 12% increase with 6b-IMRT and a 21% increase with 9b-IMRT).Compared to 3DCRT, the mean dose delivered to the contralateral kidney increased from 1.5 to 4-4.4 Gy with IMRT.The number of monitor units was increased with IMRT, especially when nine beams were used instead of six.

Conclusions

As expected, IMRT greatly reduced the high-dose irradiated volume and increased the low-dose exposure of the intestinal cavity, with a change-over around 25 Gy, compared to 3DCRT. The conformity index was compellingly better with IMRT. The integral dose delivered to the whole body was conserved with both 3DCRT and IMRT.Longer follow-up is needed to assess late toxicities to the small bowel, contralateral kidney and the risk of second cancers.     

Is concurrent radiation therapy required in patients receiving preoperative chemotherapy for adenocarcinoma of the oesophagus? A randomised phase II trial

Introduction

Preoperative chemotherapy (CT) and preoperative chemoradiation therapy (CRT) for resectable oesophageal cancer have been shown to improve overall survival in meta-analyses. There are limited data comparing these preoperative therapies. We report the outcomes of a randomised phase II trial comparing preoperative CT and CRT for resectable adenocarcinoma of the oesophagus and gastro-oesophageal junction.

Methods

Patients were randomised to receive preoperative CT with cisplatin (80 mg/m²) and infusional 5 fluorouracil (1000 mg/m²/d) on days 1 and 21, or preoperative CRT with the same drugs accompanied by concurrent radiation therapy commencing on day 21 of chemotherapy and the 5 fluorouracil reduced to 800 mg/m²/d. The radiation dose was 35 Gy in 15 fractions over 3 weeks. The endpoints were toxicity, response rates, resection (R) status, progression-free survival (PFS), overall survival (OS) and quality of life.

Results

Seventy-five patients were enroled on the study: 36 received preoperative CT and 39 preoperative CRT. Toxicity was similar for CT and CRT. Eight patients (11%) did not proceed to resection. The histopathological response rate (CRT 31% versus CT 8%, p = 0.01) and R1 resection rate (CRT 0% versus CT 11%, p = 0.04) favoured those receiving CRT. The median PFS was 14 and 26 months for CT and CRT respectively (p = 0.37). The median OS was 29 months for CT compared with 32 months for CRT (p = 0.83).

Conclusions

Despite no difference in survival, the improvement from preoperative CRT with respect to margin involvement makes this treatment a reasonable option for bulky, locally advanced resectable adenocarcinoma of the oesophagus.     

Dosimetric effect of target expansion and setup uncertainty during radiation therapy in pediatric craniopharyngioma

Purpose

Investigate the effect of tumor change and setup uncertainties on target coverage for pediatric craniopharyngioma during RT.

Methods and materials

Fifteen pediatric patients with craniopharyngioma (mean 5.1 years) were included in this study. MRI was performed before and a median of six times during RT to monitor changes in the tumor volume. IMRT plans were created and compared to the CRT plan used for treatment. The role of adaptive therapy based on GTV changes was investigated. Dosimetric effects of interfraction and intrafraction motion were examined.

Results

The mean of the maximal change in the GTV was 28.5% [−20.7% to 82.0%]. For the standard margin IMRT plans, the mean D₉₅ of the base plan on the base target was 53.6 Gy [53.1-54.1]. The mean D₉₅ of the base plans on the adaptive targets was 52.1 Gy [47.9-54.1]. The D₉₅ for the adaptive plan on the adaptive target was 53.8 Gy [53.4-54.3]. A linear regression equation of y=-0.12x , r² = 0.70, was found for the percent change in D₉₅ of the PTV (y) vs. the percent change in the GTV (x). Inter and intrafraction motion did not affect the target coverage for standard and reduced margin plans.

Conclusions

The GTV of pediatric craniopharyngioma patients change size during therapy and adaptive planning is critical for conformal plans; therefore early and regular surveillance imaging is required.     

Sequentially delivered boost plans are superior to simultaneously delivered plans in head and neck cancer when the boost volume is located further away from the parotid glands

Purpose

To find parameters that predict which head and neck patients benefit from a sequentially delivered boost treatment plan compared to a simultaneously delivered plan, with the aim to spare the salivary glands.

Methods and materials

We evaluated 50 recently treated head and neck cancer patients. Apart from the clinical plan with a sequentially (SEQ) given boost using an Intensity Modulated Radiotherapy Technique (IMRT), a simultaneous integrated boost (SIB) technique plan was constructed with the same beam set-up. The mean dose to the parotid glands was calculated and compared. The elective nodal areas were bilateral in all cases, with a boost on either one side or both sides of the neck.

Results

When the parotid gland volume and the Planning Target Volume (PTV) for the boost overlap there is on average a lower dose to the parotid gland with a SIB technique (−1.2 Gy), which is, however, not significant (p = 0.08).For all parotid glands with no boost PTV overlap, there is a benefit from a SEQ technique compared to a SIB technique for the gland evaluated (on average a 2.5 Gy lower dose to the parotid gland, p < 0.001). When the distance between gland and PTV is 0-1 cm, this difference is on average 0.8 Gy, for 1-2 cm distance 2.9 Gy and for glands with a distance greater than 2 cm, 3.3 Gy. When the lymph nodes on the evaluated side are also included in the boost PTV, however, this relationship between the distance and the gain of a SEQ seems less clear.

Conclusions

A sequentially delivered boost technique results in a better treatment plan for most cases, compared to a simultaneous integrated boost IMRT technique, if the boost PTV is more than 1 cm away from at least one parotid gland.     

Predictors of acute bowel toxicity in patients treated with IMRT whole pelvis irradiation after prostatectomy

Purpose/objective

Whole pelvis irradiation with IMRT (WPRT-IMRT) after prostatectomy is efficient in reducing acute toxicity: however, a number of patients still experience moderate acute bowel toxicity.

Materials and methods

Ninety-six patients treated with WPRT-IMRT after prostatectomy with adjuvant or salvage intent were analysed. A number of parameters were individually recovered, including the DVHs of the intestinal cavity outside PTV and of the loops referred to both the WPRT phase and the whole treatment. Correlation between clinical-dosimetric parameters and acute bowel toxicity was investigated by logistic analyses. Best predictive cut-off values for continuous variables were assessed by ROC curves.

Results

15/96 (15.6%) Patients experienced grade 2 toxicity (no grade 3). Best dose-volume predictors were the fraction of loops receiving more than 45, 50 and 55 Gy (respectively, V45TL ? 50 cc, V50TL ? 13 cc, V55TL ? 3 cc; p-values ranging from 0.005 to 0.027). Age, GU acute toxicity, rectal acute toxicity and time between prostatectomy and IMRT were also predictors of acute bowel toxicity. Multivariate analysis showed that the most predictive independent parameters were age (OR: 1.13; 95%CI: 1.02-1.25; p = 0.021) and V50TL (?13 cc, OR: 8.2; 95%CI: 1.7-40; p = 0.009).

Conclusions

The risk of moderate acute uGI toxicity during WPRT-IMRT for post-operatively treated patients increases with age; the risk is substantially reduced in patients with small overlap between PTV and loops.     

Details of recurrence sites after elective nodal irradiation (ENI) using 3D-conformal radiotherapy (3D-CRT) combined with chemotherapy for thoracic esophageal squamous cell carcinoma - A retrospective analysis

Purpose

To describe patterns of recurrence of elective nodal irradiation (ENI) in definitive chemoradiotherapy (CRT) for thoracic esophageal squamous cell carcinoma (SqCC) using 3D-conformal radiotherapy.

Methods and materials

One hundred and twenty-six consecutive patients with stages I-IVB thoracic esophageal SqCC newly diagnosed between June 2000 and July 2009 and treated with 3D-CRT in our institution were recruited from our database. Definitive CRT consisted of two cycles of nedaplatin/5FU repeated every 4 weeks, with concurrent radiation therapy of 50-50.4 Gy in 25-28 fractions. Until completion, radiotherapy was delivered to the N1 and M1a lymph nodes as ENI in addition to gross tumor volume.

Results

All 126 patients were included in this analysis, and their tumors were staged as follows: T1/T2/T3/T4, 28/18/54/26; N0/N1, 50/76; M0/M1a/M1b, 91/5/30. The mean follow-up period for the 63 surviving patients was 28.3 (±22.8) months. Eighty-seven patients (69%) achieved complete response (CR) without any residual tumor at least once after completion of CRT. After achieving CR, each of 40 patients experienced failures (local = 20 and distant = 20) and no patient experienced elective nodal failure without having any other site of recurrence. The upper thoracic esophageal carcinoma showed significantly more (34%) relapses at the local site than the middle (9%) or lower thoracic (11%) carcinomas. The 2-year and 3-year overall survival was 56% and 43%, respectively. The 1-year, 2-year and 3-year disease-free survival was 46%, 38% and 33%, respectively.

Conclusions

In CRT for esophageal SqCC, ENI was effective for preventing regional nodal failure. The upper thoracic esophageal carcinomas had significantly more local recurrences than the middle or lower thoracic sites.     

Radical prostatectomy vs. intensity-modulated radiation therapy in the management of localized prostate adenocarcinoma

Background and purpose

To determine whether radical prostatectomy (RP) or intensity-modulated radiation therapy (IMRT) to ?72 Gy, plus hormonal therapy if indicated, results in improved biochemical disease-free survival (BDFS) in localized prostate adenocarcinoma.

Materials and methods

Between 1997 and 2005, a consecutive sample of 556 patients who underwent RP (n = 204) or IMRT (n = 352) at two referral centers was analyzed. The patients were stratified into prognostic groups based on clinical stage, Gleason score, and pretreatment prostate-specific antigen (PSA). The outcome measure was BDFS.

Results

IMRT patients had more advanced disease at baseline (p < .001). There was no difference in five-year BDFS rates between RP and IMRT in the favorable (92.8% vs. 85.3%, p = .20) or intermediate prognosis (86.7% vs. 82.2%, p = .46) subsets. A difference favoring IMRT plus hormonal therapy was seen in the poor prognosis (38.4% vs. 62.2%, p < .001) subset. Within the entire cohort, after adjustment for confounding variables, Gleason score (p < .001) and clinical stage (p < .001) predicted BDFS, but treatment modality (p = .06) did not. Within the poor prognosis subset, treatment modality (p = .006) predicted BDFS.

Conclusions

BDFS is similar between RP and IMRT for patients with a favorable or intermediate prognosis. Patients with a poor prognosis display higher BDFS when treated with IMRT to ?72 Gy plus hormonal therapy.     

Volumetric modulated arc therapy versus conventional intensity modulated radiation therapy for stereotactic spine radiotherapy: A planning study and early clinical data

Background and purpose

Outcomes for selected patients with spinal metastases may be improved by dose escalation using stereotactic body radiation therapy (SBRT). As target geometry is complex, we compared SBRT plans using volumetric modulated arc radiotherapy (RapidArc®, RA) and conventional intensity-modulated radiotherapy (IMRT).

Materials and methods

RA and IMRT plans to deliver a fraction of 16 Gy to at least 90% of planning target volume (PTV) were compared for PTV coverage, normal organ sparing and estimated delivery times. Group 1 consisted of PTVs to only vertebral body (n = 3), while group 2 had PTVs encompassing the entire vertebra (n = 4). Finally, RA delivery parameters in four patients were assessed.

Results

Both techniques delivered 16 Gy to a mean of 95% and 85% of the PTV in groups 1 and 2, respectively. Spinal cord sparing was comparable; mean V_{10-partial cord} for RA and IMRT in group 1 was 3.6%, and was 9.4% versus 11.5%, respectively, in group 2. Estimated mean treatment times for RA with 2-3 arcs and IMRT were comparable. Clinical RA beam-on times ranged from 11 to 15.4 min.

Conclusions

Both RA and conventional IMRT plans deliver high quality vertebral SBRT, but plan quality was poorer when the PTV consisted of the entire vertebra.     

Planning study for available dose of hypoxic tumor volume using fluorine-18-labeled fluoromisonidazole positron emission tomography for treatment of the head and neck cancer

Purpose

To investigate the feasibility of fluorine-18-labeled fluoromisonidazole positron emission tomography/computed tomography (¹⁸F-FMISO PET/CT)-guided intensity-modulated radiotherapy (IMRT) in dose escalation to attack the hypoxic volume of a tumor mass without increasing the normal tissue dose in head and neck cancer patients.

Materials and methods

Eight consecutive head and neck cancer patients underwent ¹⁸F-FMISO PET/CT simulation. Hypoxic tumor volume (HTV) was defined using a tumor-to-cerebellum ratio (T/C) of 1.3 as the threshold for ¹⁸F-FMISO PET/CT. Dose-escalation plans for treating HTVs using ¹⁸F-FMISO PET/CT-guided IMRT were performed for these patients. The standard plan was 72 Gy to the gross tumor volume (GTV) administered as 30 daily fractions of 2.4 Gy. In biologically optimized IMRT plans, the daily dose to the HTV ranged from 2.6 to 3.6 Gy. Dose-volume histograms (DVHs) were generated as part of each plan, and the results of planning were analyzed.

Results

Dose-escalation IMRT plans, delivering 30 daily doses of 2.6 Gy (total of 78 Gy) to the HTVs without increases in normal tissue doses, were feasible for six patients. Further acceptable dose escalation on HTV depended primarily on the primary tumor site and the extent of disease.

Conclusions

It was possible to dose escalate the HTV radiation to 78 Gy in six of eight head and neck cancer patients using ¹⁸F-FMISO PET/CT-guided IMRT.     

Mesothelioma at era of helical tomotherapy: results of two institutions in combining chemotherapy, surgery and radiotherapy

Purpose

There is a scarce clinical experience about adjuvant helical tomotherapy (HT) in patients affected by malignant pleural mesothelioma (MPM) even though it appears as a useful technique to treat complex volume as the pleural cavity, and seems to have better dose distribution than the “classic” intensity modulated radiotherapy (IMRT).

Methods and materials

Twenty-four patients received adjuvant radiotherapy (RT) by HT from August 1st, 2007 to December 1st, 2009 at Curie Institute (Paris) and René Gauducheau Cancer Center (Nantes). Thirteen patients had neoadjuvant chemotherapy. Extrapleural pleuropneumonectomy (EPP) was done in 23 patients. Median dose to PTV was 50 Gy [48.7-55.9 Gy] (2 Gy/fraction). Acute and long term toxicities, disease free survival (DFS), overall survival (OS) and relapses are presented.

Results

Average follow up after RT was 7 months. The disease was staged mostly as T2-T3, N1-N2. Nineteen patients had epithelial type histology. Most patients tolerated radiotherapy with grade 1-2 side effects: redness of the skin, light cough or dyspnea, fatigue, nausea and odynophagia, mild increase of the post-operative thoracic pain. Grade 3 pneumonitis was suspected in 2 patients. Two grade 5 pneumonitis were also suspected. Eleven patients had a follow up of more than 6 months and no long term side effects related with HT were noted. At 24 months, 51.8% of patients were free of disease. Thirty percent of patients relapsed, with 2 patients presenting local relapses. Two patients died from recurrence.

Conclusion

With limited follow up, HT has comparable toxicity to those observed with traditional IMRT. Higher radiation dose and good coverage results in excellent local control.     

Induction chemotherapy with cisplatin and epirubicin followed by radiotherapy and concurrent cisplatin in locally advanced nasopharyngeal carcinoma observed in a non-endemic population

Background and purpose

Chemoradiotherapy (CRT) represents the main therapy choice in the treatment of locoregionally advanced nasopharyngeal carcinoma (NPC). The aim of this study was the clinical evaluation of neoadjuvant chemotherapy (NACT) followed by CRT in a non-endemic population affected by advanced NPC.

Materials and methods

Patients with locoregionally advanced NPC were treated with three cycles of induction chemotherapy (CHT) with cisplatin (100 mg/m²) plus epirubicin (90 mg/m²), followed by cisplatin (100 mg/m²) and concomitant radiotherapy (70 Gy).

Results

In 40 patients treated with such protocol, after the completion of induction CHT and CRT we observed the objective response rates of 90% and 100%, respectively. Treatment tolerability and toxicity were easily controllable. With a median follow-up time of 54 months, 3- and 5-year disease-free survival was 75% and 65% and 3- and 5-year overall survival was 84% and 77%.Three- and 5-year locoregional control was 82% and 70%, and 5-year distant metastases free survival was 75%.

Conclusions

NACT with cisplatin and epirubicin followed by concomitant CRT represents a feasible, efficient treatment for patients with advanced NPC. This regimen ensures an excellent locoregional disease control and overall survival with a low incidence of distant metastases.