Dose-escalation in prostate cancer: Results of randomized trials.

In 1998, an editorial from the International Journal of Radiation Oncology - Biology - Physics (IJROBP) on the occasion of the publication of Phase I by Zelefsky et al. on 3D radiotherapy dose escalation asked the question: "will more prove better?". More than 20 years later, several prospective studies have supported the authors' conclusions, making dose escalation a new standard in prostate cancer. The data from prospective randomized studies were ultimately disappointing in that they failed to show an overall survival benefit from dose escalation. However, there is a clear and consistent benefit in biochemical recurrence-free survival, which must be weighed on an individual patient basis against the potential additional toxicity of dose escalation. Techniques and concepts have become more and more precise, such as intensity modulated irradiation, simultaneous integrated boost, hypofractionated dose-escalation, pelvic irradiation with involved node boost or focal dose-escalation on gross recurrence after prostatectomy. The objective here was to summarize the prospective data on dose escalation in prostate cancer and in particular on recent advances in the field. In 2022, can we finally say that more has proven better?

[The role of proton therapy in esophageal cancer]. / Le rôle de la protonthérapie dans les cancers de l'oesophage.

Because of the physical properties of proton beam radiation therapy (PT), which allows energy to be deposited at a specific depth with a rapid energy fall-off beyond that depth, PT has several theoretical advantages over photon radiation therapy for esophageal cancer (EC). Protons have the potential to reduce the dose to healthy tissue and to more safely allow treatment of tumors near critical organs, dose escalation, trimodal treatment, and re-irradiation. In recent years, larger multicenter retrospective studies have been published showing excellent survival rates, lower than expected toxicities and even better outcomes with PT than with photon radiotherapy even using IMRT or VMAT techniques. Although PT was associated with reduced toxicities, postoperative complications, and hospital stays compared to photon radiation therapy, these studies all had inherent biases in relation with patient selection for PT. These observations were recently confirmed by a randomized phase II study in locally advanced EC that showed significantly reduced toxicities with protons compared with IMRT. Currently, two randomized phase III trials (NRG-GI006 in the US and PROTECT in Europe) are being conducted to confirm whether protons could become the standard of care in locally advanced and resectable esophageal cancers.

Brachytherapy boost (BT-boost) or stereotactic body radiation therapy boost (SBRT-boost) for high-risk prostate cancer (HR-PCa).

Systematic review for the treatment of high-risk prostate cancer (HR-PCa, D'Amico classification risk system) with external body radiation therapy (EBRT)+brachytherapy-boost (BT-boost) or with EBRT+stereotactic body RT-boost (SBRT-boost). In March 2020, 391 English citations on PubMed matched with search terms "high risk prostate cancer boost". Respectively 9 and 48 prospective and retrospective studies were on BT-boost and 7 retrospective studies were on SBRT-boost. Two SBRT-boost trials were prospective. Only one study (ASCENDE-RT) directly compared the gold standard treatment [dose-escalation (DE)-EBRT+androgen deprivation treatment (ADT)] versus EBRT+ADT+BT-boost. Biochemical control rates at 9 years were 83% in the experimental arm versus 63% in the standard arm. Cumulative incidence of late grade 3 urinary toxicity in the experimental arm and in the standard arm was respectively 18% and 5%. Two recent studies with HR-PCa (National Cancer Database) demonstrated better overall survival with BT-boost (low dose rate LDR or high dose rate HDR) compared with DE-EBRT. These recent findings demonstrate the superiority of EBRT+BT-boost+ADT versus DE-EBRT+ADT for HR-PCa. It seems that EBRT+BT-boost+ADT could now be considered as a gold standard treatment for HR-PCa. HDR or LDR are options. SBRT-boost represents an attractive alternative, but the absence of randomised trials does not allow us to conclude for HR-PCa. Prospective randomised international phase III trials or meta-analyses could improve the level of evidence of SBRT-boost for HR-PCa.

[Prognosis factors after lung stereotactic body radiotherapy for non-small cell lung carcinoma]. / Facteurs de récidive après radiothérapie stéréotaxique des cancers bronchiques non à petites cellules.

Lung cancer is the fourth most common cancer in France with a prevalence of 30,000 new cases per year. Lobectomy surgery with dissection is the gold standard treatment for T1-T2 localized non-small cell lung carcinoma. A segmentectomy may be proposed to operable patients but fragile from a respiratory point of view. For inoperable patients or patients with unsatisfactory pulmonary function tests, local treatment with stereotactic radiotherapy may be proposed to achieve local control rates ranging from 85 to 95% at 3-5 years. Several studies have examined prognostic factors after stereotaxic pulmonary radiotherapy. We conducted a general review of the literature to identify factors affecting local control.

[Moderate or extreme hypofractionation and localized prostate cancer: The times are changing]. / Hypofractionnement modéré ou extrême et cancers prostatiques localisés : les temps sont en train de changer.

There are many treatment options for localized prostate cancers, including active surveillance, brachytherapy, external beam radiotherapy, and radical prostatectomy. Quality of life remains a primary objective in the absence of superiority of one strategy over another in terms of specific survival with similar long-term biochemical control rates. Despite a significant decrease in digestive and urinary toxicities thanks to IMRT and IGRT, external radiotherapy remains a treatment that lasts approximately 2 months or 1.5 months, when combined with a brachytherapy boost. Given the specific radiosensitivity of this tumor, several randomized studies have shown that a hypofractionated scheme is not inferior in terms of biochemical control and toxicities, allowing to divide the number of fractions by a factor 2 to 8. Given that SBRT becomes a validated therapeutic option for a selected population of patients with localized prostate cancer, extreme hypofractionation is becoming a strong challenger of conventional external radiotherapy or brachytherapy.

Whole breast radiotherapy in the isocentric lateral decubitus position: Role of the immobilization device and table on clinical results.

PURPOSE: To evaluate clinical results and the "effect bolus" based on the table design of different linear accelerators in patients with breast cancer treated by previously published whole breast irradiation in the isocentric lateral decubitus position. MATERIAL AND METHODS: We studied 248 consecutive female patients with early stage breast cancer treated by conservative surgery followed by three-dimensional conformal whole breast irradiation in the isocentric lateral decubitus position between January 2013 and February 2014. Radiotherapy was performed on linear accelerators using a Varian. The energy used was 4 and 10MV photons or 6MV photons. All patients were evaluated weekly by the radiation oncologist, acute toxicity was assessed using the NCICTC v 3.0 scale. Late toxicity and cosmetic results were evaluated 18 months after the radiotherapy. Cosmetic results were defined as excellent, good, middle or bad. RESULTS: Among the 248 women included, the median age was 67 years (range: 35-91 years). All received whole breast radiotherapy with boost in 144 patients (58%). One-hundred-twenty patients received normofractionated and 124 patients hypofractionated whole breast radiotherapy. Median follow-up was 18 months. Acute skin toxicity in the whole breast radiotherapy in the isocentric lateral decubitus position was acceptable: there was 47% of grade 1 radiodermatitis, 50% of grade 2 and 3% grade 3 and no grade 4 for normofractionated radiotherapy; 89% of grade 1 dermatitis and 11% of grade 2 for hypofractionated radiotherapy; 89.7% of grade 0-1 dermatitis and 10.3% of grade 2 for the "flash" scheme and did not differ between the three linear accelerators (P=0.2, P=0.9 and P=0.2 respectively for the normofractionated radiotherapy, hypofractionated radiotherapy and the "flash"scheme). Late toxicity was acceptable with 84% of grade 0-1 fibrosis for normofractionated radiotherapy, 94% of patients for hypofractionated radiotherapy and 77% for "flash" scheme and did not differ between the three linear accelerators (P=0.44, P=1 and P=0.22 resp.). Most of patients (81%) had an excellent or a good cosmetic outcome. CONCLUSIONS: Whole breast radiotherapy in the isocentric lateral decubitus position is well tolerated. Clinical results are comparable based on different immobilization device allowed by linear accelerators. Particularly, there was no influence of the couch on skin tolerance and cosmetic results.

Patterns of locoregional failure in women with early-stage breast cancer treated by whole breast irradiation in the lateral isocentric decubitus position: Large-scale single-centre experience.

PURPOSE: The purpose of this study was to evaluate locoregional control and describe the patterns of failure in patients with breast cancer receiving whole breast radiotherapy in the isocentric lateral decubitus position technique. PATIENTS AND METHODS: In a series of 832 consecutive female patients with early-stage breast cancer including invasive and in situ tumours treated by breast-conserving surgery followed by three-dimensional conformal whole breast irradiation in the isocentric lateral decubitus position between 2005 and 2010, all patients who experienced locoregional recurrence were studied. Five-year recurrence-free and overall survival rates were calculated. Regional recurrence mapping patterns were also determined. RESULTS: The median age of this series of 832 women was 61.5 years (range: 29-90 years). Various types of fractionation were used: 50Gy in 25 fractions (17.9%), 66Gy in 33 fractions (50Gy in 25 fractions to breast followed by sequential boost to tumour bed to a total dose 66Gy in 33 fractions.) (46.5%), 40Gy in 15 fractions or 41.6Gy in 13 fractions (26.1%) and 30Gy in 5 fractions (9.5%). With a median follow-up of 6.4 years, only 36 patients experienced locoregional recurrence and no association with the fractionation regimen was identified (P=0.2). In this population of 36 patients, 28 (3.3%) had "in-breast" local recurrences (77.8%), two had local recurrences and regional lymph node recurrence (5.6%), and six had regional lymph node recurrence only (in non-irradiated areas; 16.6%). The median time to recurrence was 50 months. Complete mapping of patterns of recurrences was performed and, in most cases, local recurrences were situated adjacent to the primary tumour bed. Cases of local recurrences presented a significantly lower distant metastasis rate (P<0.001) and had a significantly longer overall survival compared to patients with regional lymph node recurrence (P<0.001). However, multivariate Cox regression analysis showed that the site of recurrence had no significant impact on overall survival (P=0.14). CONCLUSION: The results of this study indicate a low local recurrence rate. Further careful follow-up and recording of recurrences is needed to improve the understanding of patterns of recurrence.

[Normofractionated breast irradiation in breast cancer. Indications and benefits]. / Irradiation normofractionnée des cancers du sein. Indications et bénéfices.

Whole-breast normofractionated irradiation following breast-conserving surgery is the reference treatment. It delivers a dose of 50Gy in 25 fractions of 2Gy to the reference point, and, in some patients, an additional dose of 16Gy in 8 fractions of 2Gy in the tumor bed. Long-term results and toxicity of this irradiation scheme was prospectively evaluated in several randomised trials and meta-analyses, in invasive cancers as well as in ductal carcinoma in situ. The average 10-year rate of in breast recurrences was 6 % in these trials, with limited cardiac and pulmonary toxicity and limited rate of severe fibrosis. Identification of risk factors of recurrences may help to design new irradiation schemes adapted to tumor biology. The new irradiation schemes must be rigorously evaluated in the long-term in the frame of prospective clinical trials, in order to validate them as new standards of treatment.

[Adjuvant treatment of keloid scars: electrons or brachytherapy?]. / Traitement postopératoire des cicatrices chéloïdes : électrons ou irradiation interstitielle ?

PURPOSE: Evaluation of perioperative treatment of keloid scars with electron beam therapy or iridium 192 low dose rate brachytherapy. PATIENTS AND METHODS: From 1994 to 2010, 95 patients with 142 keloid scars have been treated by immediate perioperative irradiation and retrospectively reviewed in our institute: 116 scars were treated by electrontherapy and 26 by brachytherapy. RESULTS: In the electrontherapy group treated locations were: earlobe (n=88, 76%), thorax (n=14, 12%), neck (n=9, 8%), limbs (n=5, 4%). The median size of lesions was 3cm (range [R]: 0.5-18cm). In 95.6% of cases, a dose of 15Gy was delivered in five fractions of 3Gy. The median follow-up was 70 months (R: 7-161 months). The 2-year and 5-year local control were respectively 69% (95% confidence interval [95% CI]: 59-76%) and 55% (95% CI: 45-64%). In the brachytherapy group treated locations were: neck (n=3, 11%), earlobe (n=8, 32%), abdomen (n=3, 11%), thorax (n=2, 8%), limbs (n=10, 38%). The median size of lesions was 6.6cm (R: 1.7-28cm). The median dose delivered at 5mm from the source was 20Gy (R: 15-20.69). The median follow-up was 113 months (R: 21-219 months). The 2-year and 5-year local control were respectively 84.6% (95% CI: 64-94%) and 73.5% (95% CI: 49-87%). So far, no radiation-induced cancer has occurred. A trend to a better local control with brachytherapy was noted (compared to electrontherapy, 2-year relapse is halved with brachytherapy) though this difference did not reach the significance (P=0.0991), probably due to the reduced number of patients in the brachytherapy group. CONCLUSION: Brachytherapy seems to provide better local control compared to electrontherapy, and should be proposed as first line treatment. However, electrontherapy is an interesting alternative in case of difficulty to realize brachytherapy. There is probably a dose effect: according to published data, 25 to 30Gy should at least be proposed.

[Are there any dosimetric advantages in using VMAT for treatment of locally advanced non-small cell lung cancer?]. / La radiothérapie avec modulation d'intensité rotationnelle apporte-t-elle un avantage dosimétrique dans le traitement du cancer bronchique localement évolué ?

PURPOSE: To analyse the dosimetric differences between the conventional conformal radiation therapy (CR) and the volumetric modulated arc therapy (VMAT) for non-small-cell locally advanced lung cancer (NSCLC). PATIENTS AND METHODS: Two plans (CR and VMAT) were calculated for ten NSCLC patients. Dose to PTV, organs at risk and external contours (body), conformity index (PTV volume/volume of the 95% reference isodose) and homogeneity index ([maximal dose-minimal dose]/dose prescription) were compared. RESULTS: Doses delivered to PTV (homogeneity index, maximal, minimal and mean dose) are similar with both techniques but conformity index is improved by 60% with VMAT: from 0.55±0.07 with CR to 0.89±0.07 with VMAT (P=0.002). Pulmonary protection is improved with VMAT: with CR and VMAT, respectively, the mean lung dose is 14.1±5.2Gy and 12.2±4.5Gy, the lung volume which receives at least 30Gy (V30) is 20±8% and 14±5%, and the V20 is 24±11% and 20±10% (P=0.002). The mean dose received by the body is also 9% lower (P=0.004) and V5 is 13% higher (P=0.004) with VMAT. V10 and V15 were similar with both modalities. From 20Gy and higher, irradiated body volume is larger with CR than with VMAT. The relative difference increases with the dose: from 10% for 20Gy (P=0.014) up to 39% for 62.7Gy (P=0.002). CONCLUSION: Compared to CR, VMAT greatly improves conformity and reduces mean dose and dose delivered from 20Gy and higher to the lungs and the body.

[Dosimetric study of the different techniques to deal with respiratory motion for lung stereotactic radiotherapy]. / Étude dosimétrique des différentes techniques de gestion du mouvement respiratoire pour l'irradiation thoracique en conditions stéréotaxiques.

PURPOSE: To evaluate the different respiratory movement management techniques during irradiation of lung tumours. PATIENTS AND METHODS: Seven patients with one or more primary or secondary lung lesions less than 5 cm (11 tumours in total) had three computed tomographies (CT): free-breathing, deep-inspiration breath-hold using a spirometer, and 4-dimensional (4D). From these three acquisitions, five treatment plans were performed: free-breathing (reference method), deep-inspiration breath-hold, and three from the 4D CT: two breathing synchronized treatments (inspiration and expiration) and one treatment taking into account all the tumour motions (definition of the internal target volume [ITV]). Planning target volume (PTV) size and dose delivered to the lungs were compared. RESULTS: Mean PTV with the free-breathing modality was 83 ± 28 cm(3), which was significantly greater than any of the other techniques (P<0.0001). Compared to the free-breathing PTV, PTV defined with the ITV was reduced by one quarter (63 ± 31 cm(3)), and PTV with the deep-inspiration breath-hold, breathing synchronized inspiration and breathing synchronized expiration techniques were reduced by one third (50 to 54 ± 24 to 26 cm(3)). Deep-inspiration led to significantly increase the healthy lung volume compared to other methods (mean volume of 5500 ± 1500 cm(3) versus 3540 to 3920 cm(3), respectively, P<0.0001). The volume of healthy lungs receiving at least 5 and 20 Gy (V5 and V5) were significantly higher with the free-breathing method than any of the other methods (P<0.0001). The deep-inspiration breath-hold modality led to the lowest lung V5 and V20. CONCLUSION: Deep-inspiration breath-hold technique provides the most significant dosimetric advantages: small PTV and large lung volume. However, patients must be able to hold 20 seconds of apnea. Respiratory gating also reduces the PTV, but its application often requires the implantation of fiducial, which limit its use. A 4-dimensional CT allows for a personalized and reduced PTV compared to free-breathing CT.