Clinical and technical characteristics of intraoperative radiotherapy. Analysis of the ISIORT-Europe database.

BACKGROUND: A joint analysis of clinical data from centres within the European section of the International Society of Intraoperative Radiation Therapy (ISIORT-Europe) was undertaken in order to define the range of intraoperative radiotherapy (IORT) techniques and indications encompassed by its member institutions. MATERIALS AND METHODS: In 2007, the ISIORT-Europe centres were invited to record demographic, clinical and technical data relating to their IORT procedures in a joint online database. Retrospective data entry was possible. RESULTS: The survey encompassed 21 centres and data from 3754 IORT procedures performed between 1992 and 2011. The average annual number of patients treated per institution was 42, with three centres treating more than 100 patients per year. The most frequent tumour was breast cancer with 2395 cases (63.8 %), followed by rectal cancer (598 cases, 15.9 %), sarcoma (221 cases, 5.9 %), prostate cancer (108 cases, 2.9 %) and pancreatic cancer (80 cases, 2.1 %). Clinical details and IORT technical data from these five tumour types are reported. CONCLUSION: This is the first report on a large cohort of patients treated with IORT in Europe. It gives a picture of patient selection methods and treatment modalities, with emphasis on the main tumour types that are typically treated by this technique and may benefit from it.

Seroconversion and Abundance of IgG Antibodies against S1-RBD of SARS-CoV-2 and Neutralizing Activity in the Chilean Population.

COVID-19 is a pandemic caused by SARS-CoV-2. In Chile, half a million people have been infected and more than 16,000 have died from COVID-19. As part of the clinical trial NCT04384588, we quantified IgG against S1-RBD of SARS-CoV-2 (anti-RBD) in recovered people in Santiago and evaluated their suitability as COVID-19 convalescent plasma donors. ELISA and a luminescent SARS-CoV-2 pseudotype were used for IgG and neutralizing antibody quantification. 72.9% of the convalescent population (468 of 639) showed seroconversion (5-55 µg/mL anti-RBD IgG) and were suitable candidates for plasma donation. Analysis by gender, age, and days after symptom offset did not show significant differences. Neutralizing activity correlated with an increased concentration of anti-RBD IgG (p < 0.0001) and showed a high variability between donors. We confirmed that the majority of the Chilean patients have developed anti-SARS-CoV-2 antibodies. The quantification of anti-RBD IgG in convalescent plasma donors is necessary to increase the detection of neutralizing antibodies.

Breast-conserving surgery with or without radiotherapy vs mastectomy for ductal carcinoma in situ: French Survey experience.

From March 2003 to April 2004, 77 physicians throughout France prospectively recruited 1289 ductal carcinoma in situ (DCIS) patients and collected data on diagnosis, patient and tumour characteristics, and treatments. Median age was 56 years (range, 30-84). Ductal carcinoma in situ was diagnosed by mammography in 87.6% of patients. Mastectomy, conservative surgery alone (CS) and CS with radiotherapy (CS+RT) were performed in 30.5, 7.8 and 61.7% of patients, respectively. Thus, 89% of patients treated by CS received adjuvant RT. Sentinel node biopsy (SNB) and axillary dissection (AD) were performed in 21.3 and 10.4% of patients, respectively. Hormone therapy was administered to 13.4% of the patients (80% tamoxifen). Median tumour size was 14.5 mm (6, 11 and 35 mm for CS, CS+RT and mastectomy, respectively, P<0.0001). Nuclear grade was high in 21% of patients, intermediate in 38.5% and low in 40.5%. Excision was considered complete in 92% (CS) and 88.3% (CS+RT) of patients. Oestrogen receptors were positive in 69.8% of assessed cases (31%). Treatment modalities varied widely according to region: mastectomy rate, 20-37%; adjuvant RT, 84-96%; hormone treatment, 6-34%. Our survey on current DCIS management in France has highlighted correlations between pathological features (tumour size, margin and grade) and treatment options, with several similar variations to those observed in recent UK and US studies.

Concurrent trastuzumab with adjuvant radiotherapy in HER2-positive breast cancer patients: acute toxicity analyses from the French multicentric study.

BACKGROUND: Trastuzumab (T) combined with chemotherapy has been recently shown to improve outcome in HER2-positive breast cancer (BC). The aim of this study was to evaluate the toxic effects of concurrent radiation therapy (RT) and T administration in the adjuvant setting. PATIENTS AND METHODS: Data of 146 patients with stages II-III HER2-positive BC were recorded. Median age was 46 years. In all, 32 (23%) and 114 (77%) patients received a weekly and a 3-week T schedule, respectively. A median dose of 50 Gy was delivered after surgery. Internal mammary chain (IMC) was irradiated in 103 (71%) patients. RESULTS: Grade >2 dermatitis and esophagitis were noted in 51% and 12%, respectively. According to the Common Toxicity Criteria v3.0 scale and HERA (HERceptin Adjuvant) trial criteria, respectively, 10% and 6% of the patients had a grade >/=2 of left ventricular ejection fraction (LVEF) decrease after RT. Multivariate analyses revealed two independent prognostic factors: weekly T administration (for LVEF decrease) and menopausal status (for dermatitis). Higher level of T cumulative dose (>1600 mg) was only borderline of statistical significance for acute esophagitis toxicity. CONCLUSION: We showed that weekly concurrent T and RT are feasible in daily clinical practice with, however, a decrease of LVEF. Cardiac volume sparing and patient selections for IMC irradiation are highly recommended. Longer follow-up is warranted to evaluate late toxic effects.

[Accelerated partial breast irradiation in 2008: interrogations and perspectives]. / Irradiation partielle et accélérée du sein en 2008 : interrogations et perspectives.

From the beginning of 2000, accelerated and partial breast irradiation (APBI) progressively acquired maturity and used more and more sophisticated technologies. At this time, at least six international phase III trials are ongoing. The statistical design of these studies is elaborated in order to show equivalence between APBI and whole breast irradiation (WBI) in term of local control. What and when we have to wait from these randomized trials? The presented analysis discusses not only the advantages and different interrogations concerning APBI, but also the difficulties for radiation oncologists and patients to assume the long period until the publication of the ongoing phase III trial results. APBI will find its place beside WBI, as well as conservative treatment founded its place beside radical mastectomy 30 years ago. However, clinical investigation conditions appear now different and this is this difference we have to manage rigorously and precisely.

[Progress in immediate breast reconstruction with skin sparing mastectomy]. / Reconstruction mammaire immédiate: les progrès apportés par la mastectomie avec conservation de l'etui cutané

Skin sparing mastectomy (SSM) and subcutaneous mastectomy (SCM) are recent techniques. They are always associated with immediate breast reconstruction (IBR). Their safety from an oncologic point of view and indications are of great concern. In early breast cancer, SSM and SCM are associated with the same risk of local recurrence as a modified radical mastectomy, when correctly indicated. This has been validated by numerous studies. In these non-randomised studies, overall survival cannot be evaluated. Such techniques can now be validated in the oncologic setting when correctly indicated and when decision-making is always concerted and multidisciplinary. Skin-sparing techniques are obviously associated with better cosmetic results than secondary reconstructions. Thus SSM with IBR are ideally indicated for ductal carcinoma in situ, pure infiltrating or mixed carcinomas requiring mastectomy without subsequent radiotherapy. The selection criterion of no postoperative radiotherapy allows the right candidates to be chosen for SSM. But often this criterion cannot be obtained preoperatively. In such cases, performing a two-step operation could be a good option. The interval between operations can be used by the patient to obtain more information and to make a mature decision regarding her choice of treatment. It seems essential to be able to offer every patient SSM with IBR which are validated standardised indications. Such is not the case everywhere in France today. The organisation of primary care through professional networks should provide us with an opportunity to fulfil these needs.

[Accelerated partial breast irradiation: a concept to individualize treatment in breast cancer]. / Irradiation partielle et accélérée du sein: un concept pour une individualisation thérapeutique dans le cancer du sein.

Whole breast irradiation delivering an equivalent dose of 50 Gy in 5 weeks, followed by a 10 to 16 Gy-boost to the tumor bed is the standard of care after breast-conserving surgery for early-breast cancer. Accelerated partial breast irradiation (APBI) is currently under investigations in large multi-institutional, prospective, randomized trials to objectively address the critical endpoints of treatment efficacy, toxicity and cosmesis. Patient's selection for this new approach is crucial to individualise treatments and define the subgroups of patients who will really benefit from APBI in terms of quality of life without decreasing long-term results of the disease control and cosmesis. In this review, we will discuss the patients' profiles selection for APBI regarding their general and tumor criteria. The differences between APBI techniques either performed intra or post operatively will be also discussed.

Phase I-II study of two consecutive courses of high-dose epipodophyllotoxin, ifosfamide, and carboplatin with autologous bone marrow transplantation for treatment of adult patients with solid tumors.

We describe a phase I-II study of two consecutive 5-day courses of a three-drug regimen of ifosfamide (IFM), carboplatin (CBDCA), and either etoposide (VP-16) (regimen 1) or teniposide (VM-26) (regimen 2) in high doses together with autologous bone marrow transplantation (ABMT), for previously treated patients with ovarian carcinoma (OC), germ cell tumors (GCT), gestational trophoblastic disease (GTD), or oat cell carcinoma (OCC). Forty-four patients entered the study. Two patients with OC received regimen 1, and 22 were given regimen 2. Sixteen patients with GCT, two with GTD, and two with OCC were treated with regimen 1. Six patients (13%) died of toxicity. Nephropathy and esophagitis were the dose-limiting toxic effects. The maximum-tolerated doses (MTDs) were 1,500 and 200 mg/m2/d for 5 days for IFM and CBDCA, respectively, in combination with VP-16 250 mg/m2/d for 5 days (regimen 1), and 150, 1,500, and 200 mg/m2/d for 5 days for VM-26, IFM, and CBDCA, respectively (regimen 2). The response rate of patients with OC was 78% (complete response [CR], 14%). For patients previously resistant to chemotherapy, the response rate was 70%. There were no long-term disease-free survivors among patients with OC. The response rate of patients with GCT was 60% (CR, 33%). All responders with GCT were resistant to previous chemotherapy. Unmaintained CRs lasted 2, 6, 8+, 27+, and 37+ months. Of the two patients with GTD, one with previous resistance to chemotherapy attained a CR of 18+ months. One patient with OCC attained a CR lasting 6 months. The regimen possesses great antitumor activity. It produced CRs of long duration in a number of patients with GCT and GTD who were previously resistant to chemotherapy.

[Genetic bases of the radiosensitivity of breast cancer]. / Bases génétiques de la radiosensibilité des cancers du sein.

Local-regional radiation therapy is one of the major therapeutic means in the management of breast cancer. Three questions however arise from the important advances achieved in this domain in the past years. The first question concerns the possibilities to identify and overcome the radioresistance of a subset of tumours. The second question is how to recognize women likely to benefit from adjuvant radiation therapy, and therefore to diminish treatment indications in other groups. Finally, the third question is how to identify subjects at high risk for long term injury following breast irradiation, in order to adapt techniques and indications in such populations. The major advances of breast cancer molecular genetics in the past years should provide clinicians with tools to answer these important questions. In this paper, we review the molecular germline (BRCA1, BRCA2, ATM, ...) and somatic (p53, tyrosine kinase receptors, as well as actors of cell cycle, signal transduction, apoptosis, DNA repair ...) main bases of breast cancer radiosensitivity. Recent methods of exploration of the genetic background of both the host and the tumours (gene and protein expression profiles) are also reviewed as major tools of breast cancer management in the next few years.

Partial breast irradiation: revolution or evolution?

INTRODUCTION: It is well established that there is no significant difference in terms of overall survival between mastectomy and radio-surgical conservative treatment (RSCT). Ten to fifteen years have been needed to change from the "standard" to the "new" breast cancer treatment. At the end of the 1990s, a few authors published preliminary results of phase II trials using partial breast irradiation (PBI) as sole post-operative treatment based on interstitial low or high dose rate brachytherapy techniques. Currently, phase III randomized trials comparing whole breast irradiation versus PBI are ongoing in the USA and in EU. MATERIALS AND METHODS: The authors reviewed the literature regarding issues in the irradiation of breast cancer and the potential role of PBI to prevent local recurrence in the ipsilateral breast. Furthermore, potential advantages of PBI were discussed as well as the limits of such a procedure. Finally, we tried to determine the characteristics of a subgroup of patients who would receive benefit from this radiation technique. RESULTS: Phase II and III trials have been analyzed concerning feasibility, efficacy and toxicity. PBI may be delivered through low or high dose rate brachytherapy or intraoperative/external beam radiation therapy. PBI satisfies the control quality criteria. The majority of the teams provide PBI recurrence rates lower than 5% (0-4.4%) with a median follow-up varying between 8 and 72 months, and associated with cosmetic results comparable to those achieved with conventional external beam. CONCLUSION: RSCT does not replace mastectomy; mastectomy and RSCT are used together to treat different subgroups of patients. PBI furnished encouraging preliminary results in terms of local control and cosmetic results. However, caution in interpreting the results is required along with longer follow-up. PBI should not replace CT, but could be considered as a new therapeutic strategy for breast cancer dedicated to a very well defined subgroup of patients with a low risk of local recurrence.

Accelerated fractionation in esophageal cancers: a multivariate analysis on 88 patients.

PURPOSE: Accelerated fractionation was used to shorten overall treatment time to increase locoregional control and cause-specific survival. METHODS AND MATERIALS: Eighty-eight patients with cancer of the esophagus ineligible for surgery were entered in the study between 1986 and 1993. Neoadjuvant chemotherapy was given to 64% of patients. Accelerated radiotherapy using the concomitant boost technique delivered a median dose of 65 Gy in a median overall treatment time of 32 days. RESULTS: The 3-year actuarial local control rate in patients with T1, T2, and T3 tumors was 71%, 42%, and 33%, respectively. The 3-year cause-specific survival rates were 40%, 22%, and 6%, respectively. Sixteen percent of patients experienced Grade 3 esophagitis. Late toxicity included esophageal stenosis and pulmonary fibrosis in 8% and 9% of the patients, respectively. Multivariate analysis demonstrated that T stage and overall treatment time were prognostic factors for cause-specific survival. T stage and neoadjuvant chemotherapy were independent prognostic factors for locoregional control. CONCLUSION: These findings suggest that accelerated fractionation given in an overall treatment time of <35 days might be beneficial for early-stage cancer of the esophagus. Neoadjuvant chemotherapy is not recommended, as it was a significant adverse prognostic factor in the multivariate analysis for local control. Accelerated fractionation can be carried out with moderate acute and late toxicity.

High-dose-rate brachytherapy as sole modality for early-stage endobronchial carcinoma.

PURPOSE: To evaluate exclusive high-dose-rate brachytherapy for localized early-stage non-small-cell bronchial carcinoma; to develop new insights in treatment-catheter positioning and tumor-volume assessment by computed tomography (CT) scan. METHODS AND MATERIALS: Between 1992 and 1996, 34 patients with non-small-cell bronchial carcinoma were treated by brachytherapy alone. All patients were medically inoperable and had contraindications for external beam irradiation. The treatment protocol was six sessions of 5 Gy over 6 weeks. The treatment catheter was placed under fiberoscopy and was positioned with the help of spacer catheters or with a surrounding plastic tube; CT scan was performed in 50% of the cases to measure the spacing between the applicator and the bronchial wall. Dose prescription was individually based on clinical and radiologic evaluation of tumor volume. RESULTS: Local disease failure occurred in 5 patients (15%). With a median follow-up of 2 years, the local control rate was 85% and the survival rate 78%. No acute toxicity was found, except one pneumothorax. CONCLUSION: Brachytherapy alone can give an optimal therapeutic ratio in small endobronchial carcinomas without radiation-induced morbidity. Such results are achieved after careful tumor volume evaluation and individualized treatment catheter positioning.

Prescribing, recording, and reporting in endovascular brachytherapy. Quality assurance, equipment, personnel and education.

Endovascular brachytherapy is a new, rapidly growing field of interest in radiotherapy for the prevention of neointimal hyperplasia after angioplasty in both coronary and peripheral arteries. Many physics aspects of these treatments have already been addressed in the report of the American Association of Physicists in Medicine task group on 'Intravascular brachytherapy', but up to now there are no generally accepted recommendations for recording and reporting radiation doses and volumes. The terminology to be used by all individuals involved in such treatments (radiation oncologists, physicists, and interventionalists) is not clearly defined. The Endovascular Groupe Européen de Curiethérapie/European Society for Therapeutic Radiology and Oncology Working Group in this document presents recommendations for a common language for general use in endovascular brachytherapy. This proposal addresses general terms and concepts for target and dose specification as well as detailed recommendations for dose prescription, recording and reporting in endovascular brachytherapy for both peripheral and coronary arteries. Additionally, quality assurance and radiation safety aspects are briefly addressed, as are aspects related to equipment, personnel, and training and education related to endovascular brachytherapy.

Quality of life after sentinel lymph node biopsy in early breast cancer.

AIM: This study assessed the effects of multiple therapeutic factors on quality of life (QOL) in the treatment of breast cancer. METHODS: We surveyed 179 recurrence-free women with early breast cancer who had undergone a sentinel lymph node procedure, between January 1999 and June 2001. Age, tumour size, breast and axillary procedure, nodal status, chemotherapy, supra-clavicular fossa radiotherapy, and hormone therapy were tested as possible factors associated with poor QOL. RESULTS: Information on QOL was obtained for 148 out of 179 patients. Age less than 55 years and chemotherapy were factors associated with impairment of physical well-being. Tumour size was associated with poor socio-familial well-being. Factors associated with altered arm subscale scores were age <55, axillary procedure, nodal status, chemotherapy and supra-clavicular fossa radiotherapy. Unexpectedly, sentinel lymph node (SLN) procedure delayed the onset of chemotherapy if the metastatic status of SLN was not diagnosed intra-operatively. CONCLUSION: Efforts are needed to improve the QOL of young patients. Axillary procedure affects only QOL related to arm morbidity.

Radiotherapy-related fatigue: how to assess and how to treat the symptom. A commentary.

Acute and chronic radiotherapy-related fatigue occurs in up to 80% and 30%, respectively, of patients undergoing irradiation for cancer. Frequently, the symptom is not expected by the patients and is underestimated by medical and nursing staff. Fatigue can affect global quality of life more than pain, sexual dysfunction and other cancer- or treatment-related symptoms. Its etiology and correlates are not clear. Published reports are mainly descriptive, and in many of them numerous methodological biases are present. One of the limitations is lack of a standard method of assessment that could simplify the comparison between different series. In the last decade, modern instruments have been designed to measure fatigue. They include uni- and multidimensional tools. Use of these specific instruments is highly recommended for research on radiation-related fatigue. In daily practice when time is limited, simple assessment is necessary. For example, systemic use of plain and easily understandable questions about fatigue, its level and impact on daily life could be sufficient and reliable. Therapeutic strategies for radiotherapy-induced fatigue have not yet been clearly defined, but a few randomized studies have been recently published. Physical exercise, group psychotherapy and relaxation therapy have been demonstrated to be effective. Moreover, pharmacological treatment of concomitant disturbances (anemia, pain, insomnia, depression, dehydration, infection, malnutrition) and other radiotherapy side effects (diarrhea, hormonal insufficiency etc.) should be considered. Further methodologically correct studies are warranted to better define the causes, optimal prevention, assessment and management of this symptom.

Endoluminal high-dose-rate brachytherapy with a palliative aim in esophageal cancer: preliminary results at the Institut Gustave Roussy.

Ten patients with advanced esophageal carcinoma were treated with endoluminal high-dose-rate brachytherapy at the Institut Gustave Roussy. Eight of them had recurrences after external beam radiotherapy. They were treated with a high-dose rate iridium-192 source. Five patients received 6 sessions of 4 Gy, 4 patients 3 sessions of 4 Gy, and 1 patient received 3 sessions of 8 Gy. The interval time between each session was 1 week. Seventy percent of patients improved their dysphagia, with 80% endoscopic tumor response. The Karnofsky index was improved in most of the patients. The mean survival was 4 months, and dysphagia-free survival was 2.5 months. Two patients had treatment toxicity but only a transitory WHO G1 esophagitis. Endoesophageal high-dose-rate curietherapy seems an effective technique in palliative treatments. We found low toxicity and an excellent tolerance to treatment in previously irradiated patients. The efficacy of the treatment is highly dependent on a precise tumor volume evaluation.

3D-conformal radiation therapy in prostate cancer. Technical considerations after 5 years of experience and 334 patients treated at the Istituto Europeo di Oncologia of Milan, Italy.

AIMS AND BACKGROUND: To report the technique of 3D-conformal radiation therapy (3D-CRT) currently used at our Institute for the treatment of prostate cancer with a curative intent. A critical review of the technical aspects of the technique is provided. METHODS AND STUDY DESIGN: Between December 1995 and October 2000, 334 patients with biopsy-proven adenocarcinoma of the prostate were treated with 3D-CRT. All patients were treated in a prone position with 15 MV X-ray beams and a 6-field technique for all but 20 patients, who were treated with a 3-field technique. Patients were simulated with the rectum and bladder empty. To ensure reproducible positioning, custom-made polyurethane foam or thermoplastic casts were produced for each patient. Subsequently, consecutive CT scan slices were obtained. The clinical target volume and critical organs (rectum and bladder) were identified on each CT slice. The beam's eye view technique was used to spatially display these structures, and the treatment portals were manually shaped based on the images obtained. The beam apertures were initially realized by conventional Cerrobend blocks (48 patients), which were replaced in October 1997 by a computer-driven multi-leaf collimator. The total target dose prescribed at the ICRU point is 76 Gy, delivered in 38 fractions and 54 days. The seminal vesicles are excluded at 70 Gy. Dose-volume histograms were obtained for all patients. If more than 30% of the bladder and/or more than 20% of the rectum receive >95% of the prescribed total dose, the treatment plan is judged as unsatisfactory and is adjusted. The dose-volume histogram can be improved by changing the beam's arrangement and/or weights or by introducing or modifying the wedge filters. CONCLUSIONS: 3D-CRT in prostate cancer patients is a highly sophisticated and time-consuming method of dose delivery. Important technical issues remain to be clarified.

The role of low dose rate brachytherapy in the treatment of cervix carcinoma. Experience of the Gustave-Roussy Institute on 1245 patients.

From 1974 to 1992, 1245 patients with cervix carcinoma were treated at the Institut Gustave-Roussy using several treatment protocols all of which included LDR brachytherapy. We present and discuss the results of our experience.

[Brachytherapy boost for breast cancer: what do we know? Where do we go?]. / Complément d'irradiation par curiethérapie dans le cancer du sein: que savons-nous? Où allons-nous?

Since many years, Brachytherapy (BT) appears to play an important role in the treatment of many solid tumors. For breast cancer, BT is usually used as boost after postoperative external beam radiation therapy. In certain circumstances, BT can be used as sole radiation technique focalized on the tumor bed or more rarely, as second conservative treatment in case of local recurrence for woman refusing salvage mastectomy. Boost BT is most often applied via an interstitial technique while the dose rate can vary from low to high dose rate through pulse dose rate. All of those boost techniques were published and some of them compared the results obtained with BT and external beam electron therapy. The analysis of the published phase II and III trials was not able to show significant differences between the two boost techniques in term of local control as well as late skin side effects. However, we noted that the patients who received BT boost presented a higher risk of local recurrence compare to those treated with electron therapy, due to age, margin status or presence of extensive intraductal component. Only a phase III trial randomizing BT boost vs electron therapy boost could show a possible improvement of local control rate in the BT arm; however, this trial should enroll patients with a real high risk of local recurrence in order to take benefit from the dosimetric advantages of BT.