Day-care for breast cancer: ambulatory surgery and intra-operative radiation. Techniques and preliminary results of the Centre Val-d'Aurelle--Montpellier.

One-day breast carcinoma treatment is defined as association of ambulatory surgery and intra-operative irradiation. Selection and rigorous process of patients is the key to success. The surgical technique is not changed by the radiotherapy. Patient's satisfaction index is very high. Financial loss should not be a hurdle to its implementation.

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.

[Debate: Pro intraoperative radiation therapy in breast cancer]. / Débat : pour la radiothérapie peropératoire dans le cancer du sein.

The use of intraoperative radiation therapy in breast cancer patients started about 20 years ago. Several retrospective and prospective studies have been published. Intraoperative radiation therapy was initially given as a boost to the tumour bed, followed by whole-breast irradiation. These studies have demonstrated the feasibility of the technique, with local control rates and cosmetic results similar to those obtained with standard treatments. Accelerated partial breast irradiation yields local recurrence rates as low as those observed after whole-breast irradiation. Intraoperative radiation therapy as a single irradiation modality with a unique dose has been investigated in recent prospective studies showing satisfactory local results. Intraoperative radiation therapy can be proposed either as a boost or as a unique treatment in selected cases (tumour size, nodal and hormonal status, patient's age). Intraoperative radiation therapy can be delivered by orthovoltage (50 kV) X-rays from mobile generators, or by electrons from linear accelerators, mobile or fixed, dedicated or not to intraoperative radiation therapy.

[Prostate cancer]. / Cancer de la prostate.

Radiation therapy is now widely accepted as an efficacious treatment of localized prostate cancer. The technical developments of recent years have enabled the evolution of a three-dimensional conformal radiotherapy, offering a better adaptation of the dose distribution, and leading therefore to preserve organs at risk. In addition, the required dose delivered to the target volume permit physician to increase the total dose if necessary. This requires a thorough knowledge of the radio-anatomy of the prostate, the natural history of the disease but also the ballistics and dosimetry. The objectives of this work were to detail epidemiology and radio-anatomy of the prostate cancer. In addition, conformal radiation modalities are illustrated by a case report.

[Postoperative radiotherapy for prostate cancer]. / Radiothérapie postopératoire du cancer de la prostate.

More than one third of patients with localized prostate cancer at diagnosis who receive radical prostatectomy have histologically extraprostatic disease. Three randomized trials have demonstrated a significant benefit of postoperative radiotherapy for these patients in terms of biochemical progression-free survival, overall survival or metastasis-free survival in function of each study, at the cost of moderate acute and late toxicity. The technical developments of recent years have enabled the evolution of a three-dimensional conformal radiotherapy, with better adaptation of the dose distribution to the shape of target volumes to preserve organs at risk while delivering the required dose volume target. This requires a thorough knowledge of the prostate cancer radioanatomy, ballistics and dosimetry. Purpose of this work was to specify epidemiological and radioanatomy characteristics for this tumor type and conformal radiation modalities illustrated by a case report.

[Paranasal sinus carcinoma]. / Cancer des sinus de la face.

Cancers of the paranasal sinuses are rare tumors, with treatment based on a multidisciplinary approach. Surgery and radiation therapy, possibly associated with chemotherapy are used to obtain 5 years specific survival rate of 60-70 %. Advances in radiotherapy, including the use of imaging for 3D conformal approach require precise knowledge of the radioanatomy for this type of tumor to determine the different volumes of interest. Purpose of this study was to specify radioanatomy and conformal radiation modalities for cancers of the sinuses, and is illustrated by a case report.

[Which intensity modulated radiation therapy? From "step and shoot" to volumetric modulated arc therapy, point of view of the radiation oncologist]. / Quelle radiothérapie conformationnelle avec modulation d'intensité? De la technique "step and shoot" à l'arcthérapie, point de vue de l'oncologue radiothérapeute.

Intensity modulated radiation therapy (IMRT) offers optimal dosimetric and clinical results in terms of acute toxicity, allows augmenting the dose to the target volumes and therefore, appears promising for local control and disease-free survival. However, several pitfalls to this treatment are to be considered, namely a long treatment time and a high number of monitor unit (MU) required. The dosimetric results of the volumetric modulated arctherapy gives at least similar target coverage and preservation of organs at risk, while significantly reducing the number of required MUs and the overall treatment time. This has a potential impact on the treatment quality and the potential risk of secondary cancers. Volumetric modulated arctherapy allows implementation of stereotactic radiation therapy and complex treatments previously considered not feasible with IMRT. The future will involve this technology of high precision to determine the dose and to the target in real time using the image-guided radiotherapy. Tools combining these two methods are in development.

[RapidArc technology: first year of experience at the Montpellier comprehensive cancer centre]. / Arcthérapie modulée.

Intensity-modulated radiotherapy (IMRT) has highly impacted on the dose delivery thanks to inverse-planning dosimetry. Conformal isodoses to target volumes and critical organ protection have led to treatment possibilities which were unrealizable with conventional 3D technique. Nevertheless, time delivery using IMRT was in some cases longer than 3D radiotherapy. In order to compensate for this limitation, we have developed since 2007 a volumetric modulated arctherapy (RapidArc) in partnership with Varian. The technique, the results of the dosimetry plans, and quality control of the 142 first patients treated since November 2008 are presented in this review.

[Intraoperative radiotherapy: back to the future?]. / Quel avenir pour la radiothérapie peropératoire ?

Since the first Japanese publications, intraoperative radiotherapy (IORT) has been used with electrons delivered with homogeneous techniques in miscellaneous indications. The main goal was to increase the total dose in a limited volume leading to an optimized therapeutic ratio between the tumor and the healthy tissue. The main indications are not only recurrences of digestive and gynecological tumors but also retroperitoneal sarcomas. Recently, the development of the concept of partial breast irradiation reinforces the use of such a technique in the strategy of breast-conserving surgery for small tumors in the elderly. IORT was evaluated either as boost or as an exclusive treatment delivering one fraction during the surgical procedure.

[Conformal intensity modulated radiation therapy for localized prostate cancer: Toward a new standard]. / Radiothérapie de conformation avec modulation d'intensité dans le cancer de prostate : vers un nouveau standard.

Radiation therapy is now widely accepted as an efficacious treatment of localized prostate cancer. Recent advances, namely with the development of conformal radiotherapy, allowed to increase the total dose in the target volumes with greater local control. A forward step achieved with intensity modulated radiotherapy (IMRT) in terms of therapeutic ratio between target volumes and critical organs. IMRT offers an inverse planning dosimetry and a modulation of the fields during irradiation. This article presents recent technical and clinical advances in IMRT focused on prostate cancer.

The addition of a boost dose on the primary tumour bed after lumpectomy in breast conserving treatment for breast cancer. A summary of the results of EORTC 22881-10882 "boost versus no boost" trial.

PURPOSE: To investigate the impact of the boost dose to the primary tumour bed in the framework of breast conserving therapy on local control, cosmetic results, fibrosis and overall survival for patients with early stage breast cancer. PATIENTS AND METHODS: Five thousand five hundred and sixty-nine patients after lumpectomy followed by whole breast irradiation of 50 Gy were randomised. After a microscopically complete lumpectomy (5318 patients), the boost doses were either 0 or 16 Gy, while after a microscopically incomplete (251 patients) lumpectomy randomisation was between 10 and 26 Gy. The results at a median follow-up of 10 years are presented. RESULTS: At 10 years, the cumulative incidence of local recurrence was 10.2% versus 6.2% for the 0 Gy and the 16 Gy boost groups (p < 0.0001) and 17.5% versus 10.8% for the 10 and 26 Gy boost groups, respectively (p > 0.1). There was no statistically significant interaction per age group but recurrences tended to occur earlier in younger patients. As younger patients had a higher cumulative risk of local relapse by year 10, the magnitude of the absolute 10-year risk reduction achieved with the boost decreased with increasing age. Development of fibrosis was significantly dependent on the boost dose with a 10-year rate for severe fibrosis of 1.6% after 0 Gy, 3.3% after 10 Gy, 4.4% after 16 Gy and 14.4% after 26 Gy, respectively. CONCLUSION: An increase of the dose with 16 Gy improved local control for patients after a complete lumpectomy only. The development of fibrosis was clearly dose dependent. With 10 years median follow-up, no impact of survival was observed.

[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.

Increased levels of tumor markers in the follow-up of 400 patients with breast cancer without recurrence or metastasis: interpretation of false-positive results.

PURPOSE: To analyze, study and interpret the increased levels of tumor markers in breast cancer patients without recurrence or metastasis. PATIENTS AND METHODS: We studied a series of 400 patients with stage 1 breast cancer during a 3-year follow-up after primary treatment. Follow-up included frequent serum estimation of CEA, CA 15.3, CA 125, CA 27-29, TPA and TPS tumor markers. RESULTS: Of 358 patients being continuously disease-free, 18 (5%) cases showed false-positive levels of tumor markers, associated with benign conditions and not to cancer recurrence or metastasis. These conditions included ovarian cysts, thyroid disorders, hepatitis, renal stone and sarcoidosis. CONCLUSION: The value of increased tumor markers should be interpreted cautiously because it doesn't always imply disease recurrence. Tumor markers may increase in many benign conditions.

[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.

Concomitant use of tamoxifen with radiotherapy enhances subcutaneous breast fibrosis in hypersensitive patients.

Concomitant use of adjuvant tamoxifen (TAM) and radiation therapy (RT) is not widely accepted. We aim to assess whether this treatment is associated with an increased risk of developing subcutaneous fibrosis after conservative or radical surgery in breast cancer patients. We analysed 147 women with breast cancer treated with adjuvant RT, and who were included in the KFS 00539-9-1997/SKL 00778-2-1999 prospective study aimed at evaluating the predictive value of CD4 and CD8 T-lymphocyte apoptosis for the development of radiation-induced late effects. TAM (20 mg day(-1)) with concomitant RT was prescribed in 90 hormone receptor-positive patients. There was a statistically significant difference in terms of complication-relapse-free survival (CRFS) rates at 3 years, 48% (95% CI 37.2-57.6%) vs 66% (95% CI 49.9-78.6%) and complication-free survival (CFS) rates at 2 years, 51% (95% CI 40-61%) vs 80% (95% CI 67-89%) in the TAM and no-TAM groups, respectively. In each of these groups, the CRFS rates were significantly lower for patients with low levels of CD8 radiation-induced apoptosis, 20% (95% CI 10-31.9%), 66% (95% CI 51.1-77.6%), and 79% (95% CI 55-90.9%) for CD8 24%, respectively. Similar results were observed for the CFS rates. The concomitant use of TAM with RT is significantly associated with an increased incidence of grade 2 or greater subcutaneous fibrosis; therefore, caution is needed for radiosensitive patients.

[Adjuvant treatment of breast cancer by concomitant hormonotherapy and radiotherapy: state of the art]. / Hormonoradiothérapie adjuvante concomitante des cancers du sein: état de l'art.

Combining radiation and hormone therapy has become common clinical practice in recent years for locally advanced prostate cancer. The use of such concomitant therapy in the treatment of breast disease has been very infrequently reported in the literature, but such an application seems justified given the common hormonal dependence of breast cancer and the potential synergetic effect of these two treatment modalities. As adjuvant therapy, tamoxifen is the key drug in the hormonal treatment arsenal, providing a significant improvement in both local control and global survival rates. Aromatase inhibitors are currently being evaluated in this setting, and initial results are promising. In vitro, tamoxifen does not seem to offer a protective effect against radiation. In clinical use, the few available published studies confirm the superiority of the association of radiation with tamoxifen as opposed to radiation therapy alone in decreasing local recurrences of surgically removed breast tumors. Toxicity associated with such concomitant therapy includes mainly subcutaneous and pulmonary fibroses. However, subcutaneous fibrosis and its cosmetic impact on the treated breast are frequently described side effects of radiation therapy, and their incidence may actually be reduced when tamoxifen is associated. The evidence is less controversial for pulmonary fibrosis, which is more common with the concomitant therapy. The association of radiation and aromatase inhibitors has as of yet rarely been reported. Letrozole (Femara) has a radiosensitizing effect on breast-cancer cell lines transfected with the aromatase gene. Clinical data assessing this effect in vivo are not available. The FEMTABIG study (letrozole vs. tamoxifen vs. sequential treatment) did not specify the sequence of radiation and hormonal therapy. The ATAC study comparing the adjuvant use of anastrozole (Arimidex) and tamoxifen does not provide any information on the number of patients receiving radiation concomitant with the hormonal treatment, and in addition also does not specify the sequence of radiation and hormonal treatment. The TEAM study compared exemestane (Aromasine) and tamoxifen, but specified that hormonal treatment follow the completion of radiation therapy.

[Pilot study of conformal intensity modulated radiation therapy for localized prostate cancer].

PURPOSE: - To report our experience on treatment planning and acute toxicity in 16 patients suffering from clinically localized prostate cancer treated with high-dose intensity-modulated radiation therapy (IMRT). PATIENTS AND METHODS: - Between March 2001 and October 2002, 16 patients with clinically localized prostate cancer were treated with IMRT. Treatment planning included an inverse-planning approach, and the desired beam intensity profiles were delivered by dynamic multileaf collimation. All patients received the entire treatment course with IMRT to a prescribed dose of 78 Gy. All IMRT treatment plans were compared with a theoretical conventional three-dimensional conformal radiation therapy (3D-CRT). Acute lower gastro-intestinal (GI) and genito-urinary (GU) toxicity was evaluated in all patients and graded according to the Common Toxicity Criteria for Adverse Events version 3.0 (CTCAE v. 3.0). A relationship between dose volume and clinical toxicity was evaluated. RESULTS: - Ninety-five percent of the PTV2 received more than 76 Gy using IMRT or 3D-CRT with no difference between both methods. The dose-volume histogram mean obtained for the PTV2 was not different between IMRT and 3D-CRT. IMRT improved homogeneity of the delivered dose to the PTV2 as compared with 3D-CRT (7.5 vs 9%, respectively). Ninety-five percent of the PTV1 received 5 Gy more using IMRT with protection of the bladder and the rectum walls. The benefit was considered below 75 and 70 Gy for the wall of the bladder and the rectum, respectively. Grade 2 GI and GU toxicity was observed in four (25%) and five (31%) patients, respectively. No grade 3 toxicity was observed. There was a trend towards a relationship between the mean rectal dose and acute rectal toxicity but without statistical significant difference (P =0.09). CONCLUSION: - Dose escalation with IMRT is feasible with no grade 3 or higher acute GI or GU toxicity. Examination of a larger cohort and longer-term follow-up are warranted in the future.

[Concomitant use of radiotherapy and gemcitabine: preclinical findings and clinical practice]. / Association concomitante de la radiothérapie et de la gemcitabine: données précliniques et études cliniques.

Gemcitabine is pyrimidine analog which has demonstrated antitumoral activity in a variety of solid tumors. Laboratory studies demonstrating that gemcitabine is a potent radiosensitizer led to a variety of trials combining radiation and gemcitabine. In the clinic, phase I-II studies are still trying to determine the optimal dose and schedule which could be use in daily clinical practice. This review summarizes the mechanisms of interaction between radiotherapy and gemcitabine and presents several therapeutic schemes for each tumor location.

[Preliminary results of the assessment of intensity modulated radiotherapy (IMRT) for prostatic and head and neck tumors (STIC 2001)]. / Résultats préliminaires de l'évaluation de la radiothérapie conformationnelle avec modulation d'intensité (RCMI) pour le traitement des cancers prostatiques et ORL (STIC 2001).

INTRODUCTION: Between May 2002 and May 2004, eight French comprehensive cancer centres did a prospective nonrandomized study including 200 patients, 100 with cancer of the prostate and 100 with head and neck cancers. Half of each patient group was treated by IMRT and the others by RTC 3D. This clinical study was associated with an economic study and a physics study. We report here the first results. PATIENTS AND METHODS: For the clinical study, the analysis of the data of the first 88 patients irradiated for a prostatic cancer shows that 39 received RTC and 49 IMRT with a mean dose of 78 Gy at the ICRU point at 2 Gy per fraction. For H&N tumours, the preliminary analysis was done on the 87 first patients with a mean follow-up of 11.5 months (2 to 25 months) and a median of 8.4 months for the IMRT groups and 13.2 months for the RTC group. The economic study was done on the first 157 patients included during the first 18 months: 71 treated by RTC (35 for H&N and 36 for prostate) and 86 treated by IMRT (38 for H&N and 48 for prostate). The assessment of the direct costs was realized by a micro-costing technique. The physical study compared dose distributions for both techniques and has created quality control recommendations. RESULTS: Clinical studies of the acute reactions do not show any difference between groups, but we want to point out the short follow-up and the relatively high dose delivered to cancers of the prostate. The physics study demonstrates that IMRT is technically feasible in good clinical conditions with high quality assurance, a good reproducibility and precision. Dosimetric data show that IMRT could certainly spare organs at risk more than RTC for H&N tumours. The direct costs of "routine" treatments for H&N tumours were 4922 euros for IMRT versus 1899 euros for RTC and for the prostatic cancers 4911 euros for IMRT versus 2357 for RTC.

Potentiation of ionising radiation by targeting tumour necrosis factor alpha using a bispecific antibody in human pancreatic cancer.

The aim of this study was to treat carcinoembryonic antigen (CEA)-expressing pancreatic carcinoma cells with tumour necrosis factor alpha (TNFalpha) and simultaneous radiation therapy (RT), using a bispecific antibody (BAb) anti-TNFalpha/anti-CEA. TNFalpha used alone produced a dose-dependent inhibition of the clonogenic capacity of the cultured cells. Flow cytometry analysis of cell cycle progression confirmed the accumulation of cells in G(1) phase after exposure to TNFalpha. When TNFalpha was added 12 h before RT, the surviving fraction at 2 Gy was 60% lower than that obtained with irradiation alone (0.29 vs 0.73, respectively, P<0.00001). In combination treatment, cell cycle analysis demonstrated that TNFalpha reduced the number of cells in radiation-induced G(2) arrest, blocked irreversibly the cells in G(1) phase, and showed an additive decrease of the number of cells in S phase. In mice, RT as a single agent slowed tumour progression as compared with the control group (P<0.00001). BAb+TNFalpha+RT combination enhanced the delay for the tumour to reach 1500 mm(3) as compared with RT alone or with RT+TNFalpha (P=0.0011). Median delays were 90, 93, and 142 days for RT alone, RT+TNFalpha, and RT+BAb+TNFalpha groups, respectively. These results suggest that TNFalpha in combination with BAb and RT may be beneficial for the treatment of pancreatic cancer in locally advanced or adjuvant settings.