Interstitial brachytherapy for lip carcinomas: Comparison between Ir-192 low-dose-rate and high-dose-rate treatment.

PURPOSE: Low-dose-rate (LDR) and high-dose-rate (HDR) interstitial brachytherapy are known to be effective in the treatment of lip carcinomas. The aim of this study was to retrospectively compare oncologic and toxicity outcomes between the two techniques. PATIENTS AND METHODS: From 2007 to 2018, patients at the Institut de cancérologie de Lorraine (France) who received exclusive or adjuvant interstitial brachytherapy for lip squamous carcinomas were studied. Two groups were defined: the LDR/PDR group, including patients treated with iridium-192 wires, or pulsed-dose rate technique, and the high-dose-rate group, with patients treated by high-dose-rate technique. The dose ranged between 50Gy and 65Gy (depending on previous surgery) for low-dose-/pulsed-dose rate treatments, and 39Gy for high-dose-rate (twice a day). Early, late toxicity events and oncologic control were reported. RESULTS: Among the 61 patients whose data were analyzed retrospectively, 36 received the low-dose-/pulsed-dose rate treatment (59%) and 25 the high-dose-rate brachytherapy (41%). The median follow-up time was 44 months. At 36 months, the local control rates were 96.3% for LDR/PDR group and 100% for HDR (P=0.180). The regional control rates were 85.9% and 92% without any difference according to the two groups (P=0.179). The specific overall survival rate was 95.5% with no difference between groups. There were more grade 2 or higher mucositis in the HDR group than in LDR/PDR group (40% versus 16.7%, P=0.042). One case of grade 3 mucositis was recorded in each group. No grade 3 late complications were recorded. High-dose-rate brachytherapy reduced the length of hospitalization by 2 days (P<0.001). CONCLUSION: High-dose- or low-dose-/pulsed-dose rate brachytherapy seemed to be as effective and well tolerated in our experience of 61 patients.

Can we predict the cardiac benefit of deep inspiration breath hold for left breast and regional nodal irradiation?

PURPOSE: Deep inspiration breath hold (DIBH) is used to decrease the dose of radiotherapy delivered to the heart. There is a need to define criteria to select patients with the potential to derive a real clinical benefit from DIBH treatment. Our study's main goal was to investigate whether two CT-scan cardiac anatomical parameters, cardiac contact distance in the parasagittal plane (CCDps) and lateral heart-to-chest distance (HCD), were predictive of unmet dosimetric cardiac constraints for left breast and regional nodal irradiation (RNI). MATERIALS AND METHODS: This retrospective single-institution dosimetric study included 62 planning CT scans of women with left-sided breast cancer (BC) from 2016 to 2021. Two independent radiation oncologists measured HCD and CCDps twice to assess inter- and intra-observer reproducibility. Dosimetric constraints to be respected were defined, and dosimetric parameters of interest were collected for each patient. RESULTS: Mean heart dose was 7.9Gy. Inter-rater reproducibility between the two readers was considered excellent. The mean heart dose constraint<8Gy was not achieved in 25 patients (40%) and was achieved in 37 patients (60%). There was a significant correlation between mean heart dose and HCD (rs=-0.25, P=0.050) and between mean heart dose and CCDps (rs=0.25, P=0.047). The correlation between HCD and CCDps and unmet cardiac dosimetric constraints was not statistically significant. CONCLUSION: Our dosimetric analysis did not find that the cardiac anatomical parameters HCD and CCDps were predictive of unmet dosimetric cardiac constraints, nor that they were good predictors for cardiac exposure in left-sided BC radiotherapy comprising RNI.

Hypofractionated radiotherapy for invasive squamous cell carcinoma of the scalp in the elderly: Efficacy and tolerance, preliminary results.

PURPOSE: Skin squamous cells carcinomas (SCC) are frequently tumor, especially in the elderly population. Surgical excision is the standard treatment. But for patients suffering large tumor or/with comorbidity, a conservative approach with irradiation can be proposed. The hypofractionated schedule is used to shorten the overall treatment time with same results and without compromising therapeutic outcomes. The aim of this study is to assess the efficacy and tolerance of hypofractionated radiotherapy for invasive SCC of the scalp in elderly. PATIENTS AND METHODS: We included patients suffering from SCC of the scalp and treated by hypofractionated radiotherapy at the Institut de cancérologie de Lorraine or centre Émile-Durkeim d'Épinal, from January 2019 to December 2021. Characteristics of patients, size of the lesion and side effects were collected retrospectively. Tumor size at 6 months corresponded to the primary endpoint. Toxicity was collected for the secondary endpoint. RESULTS: Twelve patients with a median age of 85 years old were included. The mean size was 4,5cm with a bone invasion in 2/3 of cases. Radiotherapy was delivered after surgical excision for half of the patient. The dose delivered was 54Gy in 18 daily fractions size. Six months after irradiation: 6/11 patients had no residual lesion, 2/11 had a partial response with a residual lesion of about 1cm. 3 patients presented local recurrence. One patient died within 6 months of radiotherapy because of another comorbidity. In total, 25% had presented a grade 3 acute radiation dermatitis, no grade 4 toxicity. CONCLUSION: Short term of moderately hypofractionated schedule radiotherapy was a success with complete or partial response for more than 70% of the patients in squamous cell carcinomas. There is no major side effect.

Could conventionally fractionated radiation therapy coupled with stereotactic body radiation therapy improve local control in bone oligometastases?

PURPOSE: To describe clinical outcomes of stereotactic body radiation therapy (SBRT) applied alone or as a boost after a conventionally fractionated radiation therapy (CFRT) for the treatment of bone oligometastases. MATERIAL AND METHODS: This retrospective cohort study included patients treated with SBRT from January 2007 to December 2015 in the Institut de cancérologie de Lorraine in France. The inclusion criteria involved adults treated with SBRT for one to three bone metastases from a histological proven solid tumor and a primary tumor treated, an Eastern Cooperative Oncology Group (ECOG) score inferior or equal to 2. Local control (LC), overall survival (OS), progression free survival (PFS), bone progression incidence (BPI), skeletal related events free survival (SRE-FS), toxicity and pain response were evaluated. RESULTS: Forty-six patients and 52 bone metastases were treated. Twenty-three metastases (44.2%) received SBRT alone mainly for non-spine metastases and 29 (55.8%) a combination of CFRT and SBRT mainly for spine metastases. The median follow-up time was 22months (range: 4-89months). Five local failures (9.6%) were observed and the cumulative incidences of local recurrence at 1 and 2years respectively were 4.4% and 8% with a median time of local recurrence of 17months (range: 4-36months). The one- and two-years OS were 90.8% and 87.4%. Visceral metastasis (HR: 3.40, 95% confidence interval [1.10-10.50]) and a time from primary diagnosis (TPD)>30months (HR: 0.22 [0.06-0.82]) were independent prognostic factors of OS. The 1 and 2years PFS were 66.8% and 30.9% with a median PFS time of 18months [13-24]. The one- and two-years BPI were 27.7% and 55.3%. In multivariate analysis, unfavorable histology was associated with worse BPI (HR: 3.19 [1.32-7.76]). The SRE-FS was 93.3% and 78.5% % at 1 and 2years. The overall response rate for pain was 75% in the evaluable patients (9/12). No grade≥3 toxicity nor especially no radiation induced myelopathy (RIM), two patients developed asymptomatic vertebral compression fractures. CONCLUSION: The sole use of SBRT or its association with CFRT is an efficient and well-tolerated treatment that allows high LC for bone oligometastases.

Impact of external beam pelvic radiotherapy of endometrial carcinoma: A focus on chronic digestive toxicity.

PURPOSE: The standard treatment for endometrial cancer is surgery, although depending on the risk factors, adjuvant radiation therapy may also be given. It is proposed for high-risk carcinomas for which an improvement in progression-free survival though not overall survival has been shown. However, despite the development of radiotherapy treatments with intensity modulation and image guidance, adjuvant radiation therapy remains toxic to the digestive system. We aimed to investigate the incidence of digestive toxicity and the presence of any predictive factors. MATERIALS AND METHODS: Data were retrospectively collected from patients treated with adjuvant radiotherapy for endometrial carcinoma at the Institut de cancérologie de Lorraine and centre hospitalier Émile-Durkheim between January 2010 and October 2016 and analyzed to identify factors associated with chronic digestive toxicity. RESULTS: One hundred and thirty-nine patients received a total dose of 50Gy fractionated into 25 sessions, five per week for five weeks. The median follow-up after irradiation completion was 38 months. The incidence of gastrointestinal and rectal toxicity in all patients treated with pelvic irradiation for endometrial carcinoma was 11.1% (95% confidence interval [95%CI]: 5.4-19%) for grade 3-4 and 25.6% (95%CI: 17.0-34.9%) for grade 2-4. No factor was found to be significantly predictive of chronic digestive toxicity. At five years, the overall survival was 74.3%, (95%CI: 65.3-81.4%), progression-free survival was 69.6% (95%CI: 60.1-77.3%) and incidence of pelvic recurrence was 7.9% (95%CI: 3.8-13.9%). CONCLUSION: Our results confirmed that pelvic radiotherapy can induce a relatively high rate of digestive toxicity but failed to identify relevant factors able to predict it.

[Dose optimization in 3D pulsed dose rate brachytherapy for patients with locally advanced cervical cancer: A French multicenter phase II trial]. / Optimisation de la curiethérapie utérovaginale de débit pulsé des cancers du col utérin localement évolués : résultats finaux du PHRC Tridicol.

PURPOSE: We present the results of the PHRC Tridicol, a prospective French phase II study whose objective was to increase the dose delivered to the target volume during brachytherapy for locally advanced cervical cancers. MATERIAL AND METHODS: Eight centers included 48 patients, treated with concomitant radiochemotherapy, then uterovaginal brachytherapy. RESULTS: The median follow-up was 63 months. The dose of brachytherapy delivered in biological equivalent dose (EQD2) to 90% of the High Risk CTV (D90 CTV HR) was 80Gy in median dose. The 5-year local control rate (LC) was 84%, close to the hypothesis of 86.7%. The rate of severe complications (grade 3-4) was 23% at 5 years. The rectal dose was correlated with the risk of severe complications. CONCLUSION: HR CTV dose was below the target (85Gy) due to low use of parametrial interstitial needles, as the centers did not always have an adequate applicator, or were at the time at the beginning of their learning curve. The 5-year LC rate was improved compared to that of the comparable STIC PDR group (78%) but lower than the retroEMBRACE cohort of GEC ESTRO (89%). The complication rate was higher than in the comparable group of STIC PDR but close to that of retroEMBRACE. Training brachytherapy teams in interstitial implantation or referring patients to referral centers should help improve the therapeutic index of cervical cancer.

Interstitial multi-catheter breast brachytherapy: Technical aspects and experience feedback in a comprehensive cancer center.

PURPOSE: To focus on technical aspects of the implementation of interstitial high dose rate brachytherapy, with a step-by-step approach. MATERIALS AND METHODS: Patients were selected during multidisciplinary tumor boards, according to inclusion criteria adapted from GEC-ESTRO guidelines. A CT scan was performed a few days before implantation. On pre-implant CT, using surgical scar and clips, surgical and pathological reports, and preoperative images, we delineated the tumor bed to be included in the Clinical Target Volume (CTV), according to GEC ESTRO Recommendations. A 3D virtual implant simulation of the best catheter positions was performed in order to cover the target volume. Implantation was then carried out under local anaesthetic using 3D projections of the catheter inlets and outlets. Dosimetry was performed on post-implantation CT scan. A dose of 34Gy was delivered in 10 fractions. Acute and late side effects, and local control were evaluated 2 and 8 months after treatment. RESULTS: Between July 2017 and January 2020, 20 patients were treated with accelerated partial breast irradiation. Dose constraints regarding target volume coverage, overdose, dose homogeneity, conformation index and organs at risk were met in 94.7%, 100%, 63.2%, 0% and 89.5% of the treatment plans, respectively. Grade 1-2 acute adverse events were observed in 21% of patients, with no grade 3-4 events. CONCLUSION: The first dosimetric results and early clinical tolerance and efficacy achieved by the implementation of breast interstitial multicatheter brachytherapy in routine clinical practice are very encouraging, and confirm the interest of extending this practice.

Role of radiotherapy in the treatment of primary vaginal cancer: Recommendations of the French society for radiation oncology.

Primary vaginal cancers are rare tumours, for which external beam radiotherapy and brachytherapy are major treatment tools. Given the complexity of brachytherapy techniques, the treatment should be performed in specialised centres. We present the recommendations of the French society for radiation oncology on the indications and techniques for external beam radiotherapy and brachytherapy for primary vaginal cancer.

Prostate cancer brachytherapy: SFRO guidelines 2021.

Prostate brachytherapy techniques are described, concerning both permanent seed implant and high dose rate brachytherapy. The following guidelines are presented: brachytherapy indications, implant procedure for permanent low dose rate implants and high dose rate with source projector, as well as dose and dose-constraints objectives, immediate postoperative management, post-treatment evaluation, and long-term follow-up.

Radiotherapy of anal canal cancer.

We present the update of the recommendations of the French society for radiation oncology on external radiotherapy and brachytherapy of anal canal carcinoma. The following guidelines are presented: indications, treatment procedure, as well as dose and dose-constraints objectives, immediate postoperative management, post-treatment evaluation, and long-term follow-up.

Best practice in brachytherapy.

The 2020 recommendations for good brachytherapy procedures ("Recorad") are updated based on the 2016 article. This new brachytherapy article took into account recent data published in the literature as well as international recommendations. The different brachytherapy steps are successively described from the treatment preparation (brachytherapy technique prescription; procedure and material, dedicated images for planification, dose distribution analysis and validation) to the end of the procedure as well as post-treatment surveillance.

Hepatic tumours and radiotherapy.

We present the update of the recommendations of the French society of oncological radiotherapy on hepatic tumours. Recent technological progress led to develop the concept of focused liver radiation therapy. We must distinguish primary and secondary tumours, as the indications are restricted and must be discussed as an alternative to surgical or medical treatments. The tumour volume, its liver location close to the organs at risk determine the irradiation technique (repositioning method, total dose delivered, dose fractionation regimens). Tumour (and liver) breathing related motions should be taken into account. Strict dosimetric criteria must be observed with particular attention to the dose-volume histograms of non-tumoral liver as well as of the hollow organs, particularly in case of hypofractionated high dose radiotherapy "under stereotaxic conditions". Stereotactic body radiotherapy is being evaluated and is often preferred to radiofrequency for primary or secondary tumours (usually less than 5cm). An adaptation can be proposed, with a conformal fractionated irradiation protocol with or without intensity modulation, for hepatocellular carcinomas larger than 5cm.

Role of radiotherapy in the management of vulvar cancer: Recommendations of the French society for radiation oncology.

Primary vulvar carcinomas are rare gynaecological cancers, for which surgery is the mainstay of treatment. There is however a major place for external beam radiotherapy in the situation of inoperable locally advanced tumours and/or as adjuvant therapy, when there are risk factors for locoregional relapse. We present the recommendations of the French society for radiation oncology on the indications and techniques for radiotherapy in the treatment of primary vulvar cancer.

Rectal cancer radiotherapy.

We present the updated recommendations of the French society of oncological radiotherapy for rectal cancer radiotherapy. The standard treatment for locally advanced rectal cancer consists in chemoradiotherapy followed by radical surgery with total mesorectal resection and adjuvant chemotherapy according to nodal status. Although this strategy efficiently reduced local recurrences rates below 5% in expert centres, functional sequelae could not be avoided resulting in 20 to 30% morbidity rates. The early introduction of neoadjuvant chemotherapy has proven beneficial in recent trials, in terms of recurrence free and metastasis free survivals. Complete pathological responses were obtained in 15% of tumours treated by chemoradiation, even reaching up to 30% of tumours when neoadjuvant chemotherapy is associated to chemoradiotherapy. These good results question the relevance of systematic radical surgery in good responders. Personalized therapeutic strategies are now possible by improved imaging modalities with circumferential margin assessed by magnetic resonance imaging, by intensity modulated radiotherapy and by refining surgical techniques, and contribute to morbidity reduction. Keeping the same objectives, ongoing trials are now evaluating therapeutic de-escalation strategies, in particular rectal preservation for good responders after neoadjuvant treatment, or radiotherapy omission in selected cases (Greccar 12, Opera, Norad).

Radiotherapy for penile cancers.

Penile cancers are uncommon and should be treated in expert center. Radiotherapy indications are mainly limited to exclusive brachytherapy for early stage penile glans cancer. Brachytherapy yields to excellent outcome for disease control and organ and function preservation. Only scarce data are available for external beam radiation therapy. It could be considered as palliative setting for irradiation of the primary tumor. For lymph node irradiation, external beam radiation therapy (with or without chemotherapy) could be discussed either as neoadjuvant approach prior to surgery for massive inguinal lymph node invasion or as adjuvant approach in case of high-risk of relapse. However, these cases should be discussed on an individual basis, as the level of evidence is poor. We present the recommendations of the French Society of Oncological Radiotherapy on the indications and techniques for external beam radiotherapy and brachytherapy for penile glans cancer.

Long-term outcome of Stereotactic Body Radiation Therapy for patient with unresectable liver metastases from colorectal cancer.

PURPOSE: To investigate clinical outcome and predicting factors of local failures in patients with colorectal cancer treated for unresectable liver metastases with stereotactic body radiation therapy (SBRT). METHODS AND MATERIALS: We restrospectively reviewed the medical records of 67 patients treated with the Cyberknife SBRT system for 99 hepatic metastases between January 2007 and December 2015 in our center. In total, 37.5 to 54.0Gy in 3 to 5 fractions were prescribed to the 80% isodose line. Local control (LC), intrahepatic progression incidence, Progression-Free Survival (PFS), Overall Survival (OS) and toxicity were evaluated. RESULTS: The median follow-up was 47 months (IQR, 28-59 months). The median OS was 53 months, the 2-year OS and PFS rates were 81.4% and 54.0%. The 1- and 2-year LC rates were 86.6% and 72.4%. In the multivariate analysis, the degree of differentiation was the only prognostic factor for LC (HR 0.31, 95% CI, 0.10-0.98, P=0.046). Margin expansion>5mm was not associated with a better LC (HR 0.72, 95% CI, 0.38-1.37, P=0.317). Performans Status≥2 (HR 3.27, 95% CI, 1.07-9.98, P=0.038), chemotherapy for metastases before SBRT (HR 0.36, 95% CI, 0.18-0.75, P=0.006) and regional lymph node at diagnosis (HR 2.19, 95% CI, 1.09-4.43, P=0.029) were independent prognostic factors for OS. We report 2 cases of grade≥3 toxicity (3.0%) - one grade 3 acute nausea and one grade 3 late gastric ulcer. CONCLUSION: Stereotactic body radiation therapy is an effective and well-tolerated treatment that allow high LC for liver metastases from colorectal cancer during the first two years. A prescription dose of 45Gy in 3 fractions to the 80% isodose line with a risk adapted schedule to respect Organ At Risk constraints allows a low rate of toxicity.

[Lung cancer and pulmonary metastasis treated by stereotactic radiosurgery: Evaluation of the relevance of realisation of 3 4D CT by the RPM technique]. / Cancers et métastases bronchiques traités par irradiation stéréotaxique pulmonaire : évaluation de la pertinence de réalisation de trois scanographies quadridimensionnelles par la technique RPM.

PURPOSE: Stereotactic lung radiosurgery has been carried out in the team at the Georges-François-Leclerc centre (CGFL) in Dijon since 2008 on a Truebeam® accelerator (Varian®) with the RPM technique. MATERIALS AND METHODS: Fifty patients with primary T1-T2 stage lung cancer (n=30) or lung metastasis (n=20) were included in the study. Since 2014, 3 successive 4D scanners on D1, D2 and D3, have been produced in order to ensure the reproducibility of ITV (Internet Target Volume). The 3 ITVs are contoured (ITV 1, 2 and 3) from the MIP (Maximum Intensity Projection) of each of the 3 scanners. A global ITV is created from the ITV volumes of the 3 scanners (MIP 2 and 3 merged with MIP 1). A CBCT (Cone Beam Computerised Tomography) is performed at the start of each irradiation session to position the patient. The study consisted in analysing the relevance of the realisation of 3 different scanners before dosimetry to define the ITV and in comparing the volumes contoured on the different CBCT to the ITV to make sure that the tumour volume is well included in the ITV during the sessions. RESULTS: There is a strong correlation between the different ITVs 1, 2, 3 and global, as well as between the volumes obtained on the different CBCTs. The correlation coefficient between the different ITVs and the volumes contoured on CBCT was high for upper lobar lesions. In terms of tolerance, the FEV1 (Maximum volume expired during the first second) did not seem to be a significant factor influencing the correlation between the ITV and the volumes bypassed on CBCT. CONCLUSION: Performing a single 4D planification CT is sufficient to consider stereotactic lung irradiation, regardless of the location of the lung lesions. The correlation coefficient between ITV and CBCT was high for upper lobar lesions.

[Seeking colleagues' advice when facing complex clinical situations]. / Savoir « passer la main ¼ devant une situation complexe.

Seeking a second medical advice as a medical practitioner is a frequent situation that should be facilitated to best suit patients' expectations, while maintaining medical confidentiality. The patient and his relatives need to be involved with diagnostic and therapeutic procedures. The radiation oncologist should accept and help a patient who seeks a second advice, and patients will always appreciate when the physician helps them to seek such an advice. Examples that each practitioner should know include tertiary centers tumor boards, centers with access to innovation or clinical research, or with special teams to take care of specific populations such as adolescents and young adults. In some situations, no treatment can also be the best treatment, and it takes time to explain and discuss such watchful waiting strategies to patients. In case of recurrent disease after radiotherapy, salvage reirradiation must be discussed at a tertiary tumor board and weighed against other options, especially for rare and complex cases. Radiation oncology has gained multiple options with technological advances, such as proton therapy, brachytherapy, stereotactic body radiotherapy with respiratory tracking or contact therapy. Radiation oncologists must know the benefits associated with each option in terms of survival, local control or organ preservation in order to address patients to the best practitioner.

[Can stereotactic body radiotherapy replace brachytherapy for locally advanced cervical cancer? French society for radiation oncology statement]. / La radiothérapie stéréotaxique peut-elle remplacer la curiethérapie pour les cancers du col utérin localement évolués ? Positionnement de la Société française de radiothérapie oncologique.

Brachytherapy is part of the treatment of locally advanced cervical cancers, accounting for about half of the total delivered dose. The benefit of dose escalation is the most important in advanced cases or if the tumor has responded poorly. The use of interstitial implantations makes it possible to reach doses of the order of 85 to 90Gy (including external beam radiotherapy contribution) in most patients, through image-guided approaches. Brachytherapy delivery is one of the quality criteria for patient care. To date, no data allow us to consider as an alternative the use of external boost through intensity-modulated or stereotactic body radiotherapy. Indeed, the doses delivered to the tumor and the capacity to spare normal tissues remains lower, as compared to what is permitted by brachytherapy. It is therefore appropriate for centers that do not have access to the technique to establish networks with centers where brachytherapy is performed, to allow each patient to have access to the technique. It is also necessary to promote brachytherapy teaching. The issue of reimbursement will be crucial in the coming years to maintain expertise that is today insufficiently valued in its financial aspects, but has a very high added value for patients.

[Brachytherapy in France in 2020: State of the art and perspectives from the Groupe curiethérapie de la SFRO]. / Curiethérapie en France en 2020 : synthèse et perspectives du Groupe curiethérapie de la Société française de radiothérapie oncologique.

Because of its principle and its high proof level clinical results, brachytherapy represents a specific irradiation technique for the treatment of primary tumors as well as some local relapses in pre-irradiated area. After a glory period between the 80's and 90's, brachytherapy has progressively lost its attractiveness. In order to provide a practical solution to this deleterious situation, it is important that guardianships, health care payers, patient associations, specialist doctors and radiation oncologists understand the reasons leading to this harmful state as well as the risks concerned. A teaching judged insufficient, non-adapted value and an aging image of brachytherapy represent the three main reasons of this degradation and constitute the three most important challenges conditioning its maintain in the anticancer treatment arsenal. An adapted communication with radiation oncologists themselves but also with the other scientific societies remains crucial as well as with guardianship and patient associations. It is central that brachytherapy could be recognized in order to make it stronger and accessible for all the patients who could need it.