Symptoms 10-17 years after breast cancer radiotherapy data from the randomised SWEBCG91-RT trial

Background

Postoperative radiotherapy decreases the risk for local recurrence and improves overall survival in women with breast cancer. We have limited information on radiotherapy-induced symptoms 10-17 years after therapy.

Material and methods

Between 1991 and 1997, women with lymph node-negative breast cancer were randomised in a Swedish multi-institutional trial to breast conserving surgery with or without postoperative radiotherapy. In 2007, 10-17 years after randomisation, the group included 422 recurrence-free women. We collected data with a study-specific questionnaire on eight pre-selected symptom groups.

Results

For six symptom groups (oedema in breast or arm, erysipelas, heart symptoms, lung symptoms, rib fractures, and decreased shoulder mobility) we found similar occurrence in both groups. Excess occurrence after radiotherapy was observed for pain in the breast or in the skin, reported to occur “occasionally” by 38.1% of survivors having undergone radiotherapy and surgery versus 24.0% of those with surgery alone (absolute difference 14.1%; p = 0.004) and at least once a week by 10.3% of the radiotherapy group versus 1.7% (absolute difference 8.6%; p = 0.001). Daily life and analgesic use did not differ between the groups.

Conclusions

Ten to 17 years after postoperative radiotherapy 1 in 12 women had weekly pain that could be attributed to radiotherapy. The symptoms did not significantly affect daily life and thus the reduced risk for local recurrence seems to outweigh the risk for long-term symptoms for most women.     

Randomised phase II trial of hyperbaric oxygen therapy in patients with chronic arm lymphoedema after radiotherapy for cancer

Background

A non-randomised phase II study suggested a therapeutic effect of hyperbaric oxygen (HBO) therapy on arm lymphoedema following adjuvant radiotherapy for early breast cancer, justifying further investigation in a randomised trial.

Methods

Fifty-eight patients with ?15% increase in arm volume after supraclavicular ± axillary radiotherapy (axillary surgery in 52/58 patients) were randomised in a 2:1 ratio to HBO (n = 38) or to best standard care (n = 20). The HBO group breathed 100% oxygen at 2.4 atmospheres absolute for 100 min on 30 occasions over 6 weeks. Primary endpoint was ipsilateral limb volume expressed as a percentage of contralateral limb volume. Secondary endpoints included fractional removal rate of radioisotopic tracer from the arm, extracellular water content, patient self-assessments and UK SF-36 Health Survey Questionnaire.

Findings

Of 53/58 (91.4%) patients with baseline assessments, 46 had 12-month assessments (86.8%). Median volume of ipsilateral limb (relative to contralateral) at baseline was 133.5% (IQR 126.0-152.3%) in the control group, and 135.5% (IQR 126.5-146.0%) in the treatment group. Twelve months after baseline the median (IQR) volume of the ipsilateral limb was 131.2% (IQR 122.7-151.5%) in the control group and 133.5% (IQR 122.3-144.9%) in the treatment group. Results for the secondary endpoints were similar between randomised groups.

Interpretation

No evidence has been found of a beneficial effect of HBO in the treatment of arm lymphoedema following primary surgery and adjuvant radiotherapy for early breast cancer.     

Dosimetry audit for a multi-centre IMRT head and neck trial

Background and purpose

PARSPORT was a multi-centre randomised trial in the UK which compared Intensity-Modulated Radiotherapy (IMRT) and conventional radiotherapy (CRT) for patients with head and neck cancer. The dosimetry audit goals were to verify the plan delivery in participating centres, ascertain what tolerances were suitable for head and neck IMRT trials and develop an IMRT credentialing program.

Materials and methods

Centres enrolling patients underwent rigorous quality assurance before joining the trial. Following this each centre was visited for a dosimetry audit, which consisted of treatment planning system tests, fluence verification films, combined field films and dose point measurements.

Results

Mean dose point measurements were made at six centres. For the primary planning target volume (PTV) the differences with the planned values for the IMRT and CRT arms were −0.6% (1.8% to −2.4%) and 0.7% (2.0% to −0.9%), respectively. Ninety-four percent of the IMRT fluence films for individual fields passed gamma criterion of 3%/3 mm and 75% of the films for combined fields passed gamma criterion 4%/3 mm (no significant difference between dynamic delivery and step and shoot delivery).

Conclusions

This audit suggests that a 3% tolerance could be applied for PTV point doses. For dose distributions tolerances of 3%/3 mm on individual fields and 4%/3 mm for combined fields are proposed for multi-centre head and neck IMRT trials.     

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.     

Concomitant intensity modulated boost during whole breast hypofractionated radiotherapy - A feasibility and toxicity study

Background

Breast cancer sensitivity to large fraction size may be enhanced using hypofractionated concomitant boost radiotherapy (CBRT), thereby shortening overall treatment time. This ethics approved, prospective single cohort feasibility study was designed to evaluate the dosimetry and toxicity of CBRT using an intensity-modulated radiotherapy (IMRT) technique, compared with a standard sequential boost technique (SBT).

Methods

Fifteen women (11 right-sided; 4 left-sided) received 42.4 Gy to the whole breast and an additional 10.08 Gy to the tumor bed in 16 daily fractions, using IMRT and standard dose constraints. Each patient was replanned with the SBT, using mixed photon-electrons. Clinical target volume (CTV), dose evaluation volume (DEV), and organs at risk (OAR) dose distributions were compared with the SBT. Toxicity and treatment times were prospectively recorded.

Results

All 15 CBRT plans achieved the desired CTV (V_49.9Gy ? 99%) and DEV (V_49.9Gy ? 95%), coverage of the boost, compared with only 10 (66.7%, p = 0.03), and 12 (80%, p = 0.125) SBT plans, respectively. Ipsilateral lung (p < 0.0001), and heart (right-sided, p = 0.001; left-sided, p = 0.13) doses were lower. Grade 3 acute toxicity occurred in 1 (6.7%) patient. At 1 year, two (13.3%) additional patients had overall grade 2 late toxicity, compared with baseline. No grade 3-4 late toxicity was observed.

Conclusions

CBRT using IMRT improved boost coverage and lowered OAR doses, compared with SBT. Toxicities were acceptable using a daily boost of 3.28 Gy. While resource utilization was greater, overall treatment time was reduced.     

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.     

Subgroup analysis of patients with localized prostate cancer treated within the Dutch-randomized dose escalation trial

Purpose

To investigate the effect of dose escalation within prognostic risk groups in prostate cancer.

Patients and methods

Between 1997 and 2003, 664 patients with localized prostate cancer were randomly assigned to receive 68- or 78-Gy of radiotherapy. Two prognostic models were examined: a risk group model (low-, intermediate-, and high-risk) and PSA-level groupings. High-risk patients with hormonal therapy (HT) were analyzed separately. Outcome variable was freedom from failure (FFF) (clinical failure or PSA nadir + 2 μg/L).

Results

In relation to the advantage of high-dose radiotherapy, intermediate-risk patients benefited most from dose escalation. However no significant heterogeneity could be demonstrated between the risk groups. For two types of PSA-level groupings: PSA < 10 and ?10 μg/L, and <8, 8-18 and >8 μg/L, the test for heterogeneity was significant (p = 0.03 and 0.05, respectively). Patients with PSA 8-18 μg/L (n = 297, HR = 0.59) derived the greatest benefit from dose escalation. No heterogeneity could be demonstrated for high-risk patients with and without HT.

Conclusion

Intermediate-risk group derived the greatest benefit for dose escalation. However, from this trial no indication was found to exclude low-risk or high-risk patients from high-dose radiotherapy. Patients could be selected for high-dose radiotherapy based on PSA-level groupings: for patients with a PSA < 8 μg/L high-dose radiotherapy is probably not indicated, but should be confirmed in other randomized studies.     

A significant decrease in rectal volume and diameter during prostate IMRT

Purpose

To record changes in rectal volume (RV) and diameter (RD) of patients with prostate adenocarcinoma prior to and at an interim period during radiotherapy, which could potentially affect treatment toxicity and tumor control.

Methods

Three hundred and fifteen patients treated with intensity modulated radiotherapy (IMRT) underwent planning CT scans before radiation and after 45 Gy. For each scan, RV and RD were recorded and compared using a two-tailed paired t-test. Robust linear regression analysis assessed correlation between initial RV and percent RV change.

Results

The mean change in RV was −8.62 cm³ and in RD was −0.19 cm³, (p < 0.05). A decrease ?10% in RV and RD was seen in 159 patients (50.5%) and 117 patients (37.1%), respectively. Patients with ?10% volume change had larger initial RVs than those with <10% decrease, (78.1 vs. 50.8 cm³, p < 0.0001).

Conclusions

A significant decrease in RV and RD occurs during prostate IMRT delivery. More than half of patients had decreased RV and over a third had decreased RD. This observation is pertinent to prostate localization, planning margins, and implies that dose-volume histogram (DVH) analysis of rectal irradiation based on pre-treatment CT scanning may inaccurately estimate the risk of rectal toxicity when the initial RV is larger than 70 cm³.     

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.     

Stereotactic radiotherapy for peripheral lung tumors: A comparison of volumetric modulated arc therapy with 3 other delivery techniques

Purpose

Volumetric modulated arc therapy (RapidArc) allows for fast delivery of stereotactic body radiotherapy (SBRT) delivery in stage I lung tumors. We compared dose distributions and delivery times between RapidArc and common delivery techniques in small tumors.

Methods

In 18 patients who completed RapidArc SBRT for tumors measuring <70 cm³, new treatment plans were generated using non-coplanar 3D conformal fields (conf-SBRT) and dynamic conformal arc radiotherapy (DCA). For 9 patients with tumors adjacent to the chest wall, co-planar intensity-modulated radiotherapy (IMRT) plans were also generated. PTV dose coverage, organs at risk (OAR) doses and treatment delivery times were assessed.

Results

RapidArc plans achieved a superior conformity index (CI) and lower V_45Gy to chest wall (p < 0.05) compared to all other techniques. RapidArc led to a small increase in V_5Gy to contralateral lung compared to conf-SBRT (4.4 ± 4% versus 1.2 ± 1.8%, p = 0.011). For other OAR, RapidArc and conf-SBRT plans were comparable, and both were superior to DCA plans. Delivery of a 7.5 Gy-fraction required 3.9 min (RapidArc), 11.6 min (conf-SBRT), and 12 min (IMRT).

Conclusions

In stage I lung tumors measuring <70 cm³, RapidArc plans achieved both the highest dose conformity and shortest delivery times.     

Managing supraclavicular disease from breast cancer with brachial plexus-sparing techniques using helical tomotherapy

Aims

Managing supraclavicular fossa (SCF) disease in patients with breast cancer can be challenging, with brachial plexopathy recognised as a complication of high-dose radiotherapy to the SCF. Local control of SCF disease is an important end point. Intensity-modulated radiotherapy (IMRT) techniques provide a steep dose gradient and improve the therapeutic index, making it possible to escalate dose to planning target volumes (PTVs), while reducing the dose to organs at risk (OAR). We explored image-guided IMRT techniques using helical tomotherapy to dose escalate SCF lymph nodes with a view to restrict the dose to the brachial plexus.

Materials and methods

Three cases with SCF nodal disease in varying clinical stages of breast cancer were planned and treated using helical tomotherapy-IMRT to assess the feasibility and safety of radiotherapy dose escalation to improve the chances of local control in SCF while restricting the dose to the brachial plexus. Consultant clinical oncologists were asked to define the PTVs and OARs as per agreed inhouse policy. The brachial plexus was outlined as a separate OAR in all three cases. In case 1 the left breast and SCF were treated with adjuvant radiotherapy (40 Gy in 15 fractions) with a sequential boost (10 Gy in five fractions) to the SCF PTV. In case 2, local recurrence was salvaged using a simultaneous integrated boost to the gross tumour plus a 3 mm margin to 63 Gy and 54 Gy to the entire SCF. Case 3 was to control nodal disease with re-irradiation of the SCF to a median dose of 44 Gy, while maintaining a low dose to the brachial plexus. Inverse planning constraints (helical tomotherapy) were applied to the PTV and OARs with the brachial plexus allowed a maximum biologically effective dose (BED) of 120 Gy.

Results

It was possible to treat the SCF to a higher dose using helical tomotherapy-IMRT. The treatment was successful in controlling disease in the SCF. No patients reported symptoms suggestive of brachial plexopathy.

Conclusion

Sequential or simultaneous integrated boost to the SCF was safe and feasible. This is the first publication of dose escalation to the SCF when treating breast cancer with brachial plexus-sparing IMRT techniques. The feasibility of such techniques warrants a multicentre phase II study of dose escalation with IMRT to improve local control in isolated SCF disease.     

The role of ipsilateral breast radiotherapy in management of occult primary breast cancer presenting as axillary lymphadenopathy

Aim

To assess the role of ipsilateral breast radiotherapy (IBR) in women with occult primary breast cancer presenting with axillary metastases (OPBC).

Methods

Patients with axillary nodal metastases and histological diagnosis of breast cancer without palpable, mammographic or ultrasonographic evidence of a breast primary were identified from a prospectively maintained single institution database. Imaging, surgery, radiotherapy, recurrence and survival data were collected. Patients whose breast cancer primary was detected on MRI (but occult on clinical examination and other imaging) were excluded from the analyses of IBR and outcome, but were included in other exploratory analyses.

Results

Fifty-five patients were included between 1975 and 2009. Median follow up was 68 months. Twenty patients had breast magnetic resonance imaging (MRI) in addition to other imaging. A primary breast cancer was detected in 7 of these 20. 48/55 patients had no detectable breast primary. 35/48 patients (73%) were treated with radiotherapy to the conserved breast, and 13/48 (27%) with observation. Patients who had IBR had better 5 year local recurrence free survival (LRFS) (84% versus 34%, p < 0.001), and relapse free survival (RFS) (64% versus 34%, p = 0.05), but no difference in overall survival (OS) (84% versus 85%, p = 0.2). There was no difference in 5 year LRFS (80% versus 90%: p = 0.3) between patients who received radiation of 50 Gy in 25 fractions versus ?60 Gy.

Conclusion

Patients with OPBC should be managed with IBR and breast conservation, or mastectomy. Our data suggest it is not necessary to irradiate the breast to more than 50 Gy in 25 fractions.     

Dose-response relations for stricture in the proximal oesophagus from head and neck radiotherapy

Background and purpose

Determination of the dose-response relations for oesophageal stricture after radiotherapy of the head and neck.

Material and methods

In this study 33 patients who developed oesophageal stricture and 39 patients as controls are included. The patients received radiation therapy for head and neck cancer at Karolinska University Hospital, Stockholm, Sweden. For each patient the 3D dose distribution delivered to the upper 5 cm of the oesophagus was analysed. The analysis was conducted for two periods, 1992-2000 and 2001-2005, due to the different irradiation techniques used. The fitting has been done using the relative seriality model.

Results

For the treatment period 1992-2005, the mean doses were 49.8 and 33.4 Gy, respectively, for the cases and the controls. For the period 1992-2000, the mean doses for the cases and the controls were 49.9 and 45.9 Gy and for the period 2001-2005 were 49.8 and 21.4 Gy. For the period 2001-2005 the best estimates of the dose-response parameters are D₅₀ = 61.5 Gy (52.9-84.9 Gy), γ = 1.4 (0.8-2.6) and s = 0.1 (0.01-0.3).

Conclusions

Radiation-induced strictures were found to have a dose response relation and volume dependence (low relative seriality) for the treatment period 2001-2005. However, no dose response relation was found for the complete material.     

Comparison of three-dimensional versus intensity-modulated radiotherapy techniques to treat breast and axillary level III and supraclavicular nodes in a prone versus supine position

Background and purpose

To determine the optimal method of targeting breast and regional nodes in selected breast cancer patients after axillary dissection, we compared the results of IMRT versus no IMRT, and CT-informed versus clinically-placed fields, in supine and prone positions.

Materials and methods

Twelve consecutive breast cancer patients simulated both prone and supine provided the images for this study. Four techniques were used to target breast, level III axilla, and supraclavicular fossa in either position: a traditional three-field three-dimensional conformal radiotherapy (3DCRT) plan, a four-field 3DCRT plan using a posterior axillary boost field, and two techniques using a CT-informed target volume consisting of an optimized 3DCRT plan (CT-planned 3D) and an intensity-modulated radiotherapy (IMRT) plan. The prescribed dose was 50 Gy in 25 fractions.

Results

CT-planned 3D and IMRT techniques improved nodal PTV coverage. Supine, mean nodal PTV V50 was 50% (3-field), 59% (4-field), 92% (CT-planned 3D), and 94% (IMRT). Prone, V50 was 29% (3-field), 42% (4-field), 97% (CT-planned 3D), and 95% (IMRT). Prone positioning, compared to supine, and IMRT technique, compared to 3D, lowered ipsilateral lung V20.

Conclusions

Traditional 3DCRT plans provide inadequate nodal coverage. Prone IMRT technique resulted in optimal target coverage and reduced ipsilateral lung V20.     

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.     

Evaluation of the impact of dental artefacts on intensity-modulated radiotherapy planning for the head and neck

Background and purpose

High density materials create severe artefacts in the computed tomography (CT) scans used for radiotherapy dose calculations. Increased use of intensity-modulated radiotherapy (IMRT) to treat oropharyngeal cancers raises concerns over the accuracy of the resulting dose calculation. This work quantifies their impact and evaluates a simple corrective technique.

Materials and methods

Fifteen oropharyngeal patients with severe artefacts were retrospectively planned with IMRT using two different CT/density look-up tables. Each plan was recalculated using a corrected CT dataset to evaluate the dose distribution delivered to the patient. Plan quality in the absence of dental artefacts was similarly assessed. A range of dosimetric and radiobiological parameters were compared pre- and post-correction.

Results

Plans using a standard CT/density look-up table (density ?1.8 g/cm³) revealed inconsistent inter-patient errors, mostly within clinical acceptance, although potentially significantly reducing target coverage for individual patients. Using an extended CT/density look-up table (density ?10.0 g/cm³) greatly reduced the errors for 13/15 patients. In 2/15 patients with residual errors the CTV extended into the severely affected region and could be corrected by applying a simple manual correction.

Conclusions

Use of an extended CT/density look-up table together with a simple manual bulk density correction reduces the impact of dental artefacts on head and neck IMRT planning to acceptable levels.     

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.     

Long-term follow-up of cancer patients receiving radiotherapy for bone metastases: Results from a randomised multicentre trial

Background and purpose

The aim of this study was to compare the need for re-irradiation, rates of pathological fractures, and spinal cord compressions in patients randomised to single-fraction radiotherapy (8 Gy × 1) or multiple-fraction therapy (3 Gy × 10) and with a long-term follow-up. The underlying hypothesis was that single-fraction and multiple-fraction regimens are equally effective.

Material and methods

The present study reports on the Norwegian sub sample of an international large prospective-randomised multicentre study. One hundred and eighty patients with painful skeletal metastases in four Norwegian hospitals were randomised to receive single-fraction (8 Gy × 1) or multiple-fraction (3 Gy × 10) radiotherapy.

Results

Patients in the single-fraction arm received significantly more re-irradiations as compared to the multiple-fraction arm (27% versus 9%, p = 0.002). There were no significant differences in the rate of pathological fractures (5% versus 5%, p = 1.00) or spinal cord compressions (1% versus 4%, p = 0.37) between the two treatment groups.

Conclusion

The present study indicates no difference between radiotherapy with 8 Gy × 1 and 3 Gy × 10 for the majority of patients with painful bone metastases, also in a long-term perspective. Importantly, the patients in this study were followed up until death, and the trial showed no disadvantage for 8 Gy × 1 compared to 3 Gy × 10. Despite the fact that single-fraction treatment will imply an approximately 2.5-fold greater need for re-irradiation, single-fraction treatment is considered more convenient for the patients and more cost-effective for the radiotherapy departments.     

Phase I dose escalation trial of hypofractionated limited-field external beam thoracic radiotherapy for limited-stage small cell carcinoma of the lung

Purpose

To define the maximal tolerated dose of hypofractionated thoracic radiotherapy given with concurrent chemotherapy for limited-stage small cell lung cancer.

Materials and methods

Limited-stage small cell lung cancer patients were prescribed 54, 58, 62 or 65 Gy, all given in 25 daily fractions and commenced on or before the second chemotherapy cycle. Dose level accrual was performed sequentially. Conformal radiotherapy techniques were used and targeted gross disease plus margin. Four cycles of platinum-based chemotherapy were prescribed. Primary endpoint was the rate of acute RT toxicities according to NCI Common Toxicity Criteria scales. The dose which caused unacceptable acute radiotherapy toxicity rates according to pre-defined stopping rules defined the maximal tolerated radiotherapy dose.

Results

Six patients were accrued to each of the 54, 58 and 62 Gy dose levels. There were no radiotherapy-related deaths. No grade 3 toxicities occurred in the 54 and 58 Gy groups. There were 2 grade 3 RT toxicities in the 62 Gy group. There were 14 complete responses. Trial accrual has stopped at the 62 Gy group according to trial stopping rules.

Conclusions

The maximal tolerated hypofractionated thoracic radiotherapy dose in this trial was 58 Gy in 25 daily fractions.