[Recommendations in the use of portal images]. / Recommandations pour l'utilisation des images de contrôle.

Technical radiotherapy progress drive the practices towards increasingly more precise irradiations. The recent developments of the various imaging methods and specialized software made more controls possible. The fields of investigations relate to the quality assurance of the irradiation, the reproducibility of positioning, the movements evaluations and real time dosimetry. Radiotherapy finds, in the images exploitation, a strong potential in improving quality treatments, however it is conditioned by the implementation of ambitious programs, time consuming, but essential to grant the precision of virtual simulations and the daily practice. If all the existing technical devices and software offer higher tools than the current practices, the recommendations can be limited to the insurance of a sufficient precision and reproducibility of the whole treatments. It is thus fundamental to be able to filter the errors, the systematic deviations and to control the statistics of positioning and movements. Each radiotherapy department must apply an adapted program to each site and exploit the imaging chain to maintain its results.

[Dose-response relationship in radiotherapy: an evidence?]. / Effet dose en radiothérapie: une évidence?

The dose-response relationship is a fundamental basis of radiobiology. Despite many clinical datas, difficulties remain to demonstrate a relation between dose and local control: relative role of treatment associated with radiation therapy (surgery, chemotherapy, hormonal therapy), tumor heterogeneity, few prospective randomized studies, uncertainty of local control assessment. Three different situations are discussed: tumors with high local control probabilities for which dose effect is demonstrated by randomized studies (breast cancer) or sound retrospective datas (soft tissues sarcomas), tumors with intermediate local control probabilities for which dose effect seems to be important according to retrospective studies and ongoing or published phase III trials (prostate cancer), tumors with low local control probabilities for which dose effect appears to be modest beyond standard doses, and inferior to the benefit of concurrent chemotherapy (lung and oesophageal cancer). For head and neck tumors, the dose-response relationship has been explored through hyperfractionation and accelerated radiation therapy and a dose effect has been demonstrated but must be compared to the benefit of concurrent chemotherapy. Last but not least, the development of conformal radiotherapy allow the exploration of the dose response relationship for tumors such as hepatocellular carcinomas traditionally excluded from the field of conventional radiation therapy. In conclusion, the dose-response relationship remains a sound basis of radiation therapy for many tumors and is a parameter to take into account for further randomized studies.

[Respiration-gated radiotherapy: current techniques and potential benefits]. / La radiothérapie asservie à la respiration: techniques actuelles et bénéfices attendus.

Respiration-gated radiotherapy offers a significant potential for improvement in the irradiation of tumor sites affected by respiratory motion such as lung, breast and liver tumors. An increased conformality of irradiation fields leading to decreased complications rates of organs at risk (lung, heart...) is expected. Respiratory gating is in line with the need for improved precision required by radiotherapy techniques such as 3D conformal radiotherapy or intensity modulated radiotherapy. Reduction of respiratory motion can be achieved by using either breath hold techniques or respiration synchronized gating techniques. Breathhold techniques can be achieved with active, in which airflow of the patient is temporarily blocked by a valve, or passive techniques, in which the patient voluntarily breath-hold. Synchronized gating techniques use external devices to predict the phase of the respiration cycle while the patient breaths freely. These techniques presently investigated in several medical centers worldwide. Although promising, the first results obtained in lung and liver cancer patients require confirmation. Physical, technical and physiological questions still remain to be answered. This paper describes the most frequently used gated techniques and the main published clinical reports on the use of respiration-gated radiotherapy in order to evaluate the impact of these techniques.

[Prostate cancer: has local radiation treatment had an impact on survival?]. / Cancers de prostate: le traitement local par irradiation a-t-il un impact sur la survie?

Local control is an important goal in the treatment of prostate cancer. Firstly, it avoids the morbidity due to locoregional evolution (urethral obstruction, vascular compression, rectal or vesical involvement). Moreover, local control of the disease may decrease the mortality due to metastases disseminated from local relapse. Local control evaluation remains difficult: neither rectal examination nor imaging or prostate biopsies have an absolute value in diagnostic of local relapse. PSA increase does not permit to differentiate local from distant relapses. Recent developments in radiotherapy techniques allow dose escalation without major toxicity. Retrospective studies and one randomized study have shown that an increase from 70 to 80 Gy or more, improve biological relapse-free survival. In one randomized study comparing 70 to 78 Gy, the biochemical disease-free survival was improved from 69 to 79% at five years. Such an improvement can only be explained by an improvement of local control. The benefit in term of overall survival is not yet demonstrated and needs a longer follow-up and other studies. Another approach to improve local control is the association of a local radiotherapy with hormonal adjuvant therapy. Four randomized studies have been published for locally advanced prostate cancer. These studies have all demonstrated an improvement of local control, and a decrease of metastatic risk. The benefit in term of overall survival, observed in one of this trial, may be explained by the improvement of either local or distant control or both. Such therapeutic progress, associated with the development of prostate cancer screening should lead to a decrease of prostate cancer mortality for the next ten years.

[Radiotherapy of lung cancer: the inspiration breath hold with spirometric monitoring]. / Radiothérapie des cancers du poumon: le blocage en inspiration sous contrôle spirométrique.

A CT acquisition during a free breathing examination generates images of poor quality. It creates an uncertainty on the reconstructed gross tumour volume and dose distribution. The aim of this study is to test the feasibility of a breath hold method applied in all preparation and treatment days. Five patients received a thoracic radiotherapy with the benefit of this procedure. The breathing of the patient was measured with a spirometer. The patient was coached to reproduce a constant level of breath-hold in a deep inspiration. Video glasses helped the patients to fix the breath-hold at the reference level. The patients followed the coaching during preparation and treatment, without any difficulty. The better quality of the CT reconstructed images resulted in an easier contouring. No movements of the gross tumour volume lead to a better coverage. The deep breath hold decreased the volume of irradiated lung. This method improves the reproducibility of the thoracic irradiation. The decrease of irradiated lung volume offers prospects in dose escalation and intensity modulation radiotherapy.

[Thoracic radiotherapy and control of respiration: current perspectives]. / Radiothérapie thoracique et contrôle de la respiration: perspectives actuelles.

Three-dimensional conformal radiotherapy (3D CRT) is adversely affected by setup error and organ motion. In thoracic 3D CRT, breathing accounts for most of intra-fraction movements, thus impairing treatment quality. Breath control clearly exhibits dosimetric improvement compared to free breathing, leading to various techniques for gated treatments. We review benefits of different breath control methods--i.e. breath-holding or beam gating, with spirometric, isometric or X-ray respiration sensor--and argument the choice of expiration versus inspiration, with consideration to dosimetric concerns. All steps of 3D-CRT can be improved with breath control. Contouring of organs at risk (OAR) and target are easier and more accurate on breath controlled CT-scans. Inter- and intra-fraction target immobilisation allows smaller margins with better coverage. Lung outcome predictors (NTCP, Mean Dose, LV20, LV30) are improved with breath-control. In addition, inspiration breath control facilitates beam arrangement since it widens the distance between OAR and target, and leaves less lung normal tissue within the high dose region. Last, lung density, as of CT-scan, is more accurate, improving dosimetry. Our institution's choice is to use spirometry driven, patient controlled high-inspiration breath-hold; this technique gives excellent immobilization results, with high reproducibility, yet it is easy to implement and costs little extra treatment time. Breath control, whatever technique is employed, proves superior to free breathing treatment when using 3D-CRT. Breath control should then be used whenever possible, and is probably mandatory for IMRT.

[Are there physical, technical and morphological limits to conformational radiotherapy?]. / Y a-t-il des limites physiques, techniques et morphologiques à la radiothérapie conformationnelle?

Conformal radiotherapy results from several technical and data processing advances. The treatment planning and the daily treatments have benefited from a significant improvement of the quality control. However, all the steps of the process contain various limitations of varying effects. It appear important to identify, describe and exploit those limits to better drive the procedures and optimise the quality. Identifying the limits of the conformal radiotherapy should be an important help to implement intensity modulation radiotherapy.

[Dosimetric evaluation of conformal radiotherapy: conformity factor]. / Evaluation dosimétrique d'une radiothérapie conformationnelle: le facteur de conformation.

The aim of three-dimensional conformal therapy (3DCRT) is to treat the Planning Target Volume (PTV) to the prescribed dose while reducing doses to normal tissues and critical structures, in order to increase local control and reduce toxicity. The evaluation tools used for optimizing treatment techniques are three-dimensional visualization of dose distributions, dose-volume histograms, tumor control probabilities (TCP) and normal tissue complication probabilities (NTCP). These tools, however, do not fully quantify the conformity of dose distributions to the PTV. Specific tools were introduced to measure this conformity for a given dose level. We have extended those definitions to different dose levels, using a conformity index (CI). CI is based on the relative volumes of PTV and outside the PTV receiving more than a given dose. This parameter has been evaluated by a clinical study including 82 patients treated for lung cancer and 82 patients treated for prostate cancer. The CI was low for lung dosimetric studies (0.35 at the prescribed dose 66 Gy) due to build-up around the GTV and to spinal cord sparing. For prostate dosimetric studies, the CI was higher (0.57 at the prescribed dose 70 Gy). The CI has been used to compare treatment plans for lung 3DCRT (2 vs 3 beams) and prostate 3DCRT (4 vs 7 beams). The variation of CI with dose can be used to optimize dose prescription.

[Radiotherapy of localized prostatic cancer: follow-up of 48 patients. G.C.C.P. (Cooperative Group for the Study of Prostatic Cancer)]. / Radiothérapie des cancers de prostate localisés: 48 malades suivis plus de dix ans. G.C.C.P. (Groupe Coopératif d'Etude du Cancer de la Prostate).

OBJECTIVE: To evaluate the safety and long-term efficacy of curative-intent radiation therapy in patients with apparently localized prostate cancer. METHOD: 48 patients with T < 3 M0 prostate cancer recruited between 1981 and 1985 received regular clinical follow-up for at least ten years or until their death. Radiation therapy was given according to the protocols established by Ray and Bagshaw. RESULTS: Radiation therapy was safe and effective in most patients. The rate of escape phenomenon was less than 10% after two years. Tumor control rates were greater than 80% after five years and 50% after ten years. Unfortunately, local remission, even when prolonged, did not necessarily indicate a complete cure: 20% of local recurrences developed five to 11 years after radiation therapy. CONCLUSION: Radiation therapy may be the best first-line treatment in men older than 75 years of age and in those whose life expectancy seems shorter than ten years, but should probably not be considered curative.

[Definition of prostatic contours using tomodensitometric slices: study of differences among radiotherapists and between examinations]. / Définition des contours prostatiques sur coupes tomodensitométriques: étude des discordances entre radiothérapeutes et entre examens.

Accuracy of conformal treatment planning for prostatic radiotherapy is based on the contours of target volumes (prostate +/- seminal vesicles) and normal tissues (rectum and bladder), drawn on CT (computed tomography) images by radiation oncologists. The interpretation of a given CT image can be different from one radiation oncologist to another, and may change in time with the state of filling of the bladder and of the rectum during the treatment. In order to quantify these variations, 12 patients treated with conformal radiotherapy for prostate carcinoma (pelvis 40 Gy/20 sessions + prostate 30 Gy/15 sessions) had two series of CT at one month intervals. Contouring of prostate, rectum and bladder were performed independently on each CT by two radiation oncologists. The first CT scan (planning CT) and the first series of contours (planning contours) were used for treatment planning. The contours of the second scan were compared to the planning contours after image fusion based on manual superimposition of bony anatomy of the two sets of CT images. Coherence ratio were defined to measure discrepancies in prostate volumes between radiation oncologists (RCE) and between scans (RCT). The mean RCE was 38 +/- 7% (1 standard deviation). Those discrepancies were primarily located at the prostate apex and at the interface between bladder and prostate and between rectum and prostate. The mean RCT was 42 +/- 8% (1 sigma). Those discrepancies were due to the prostate motion related to the state of filling of the rectum and bladder. For bladder and rectal walls, less important differences were observed between the two radiation oncologists for the same CT (4.5% for rectal volume receiving 65 Gy or more, 3% for bladder volume receiving 65 Gy or more). However, important differences in bladder and rectal volumes receiving 65 Gy or more (16% and 7% respectively) were noted for the same patient from a CT to another due to the variation in bladder or rectal filling. New techniques for planning CT acquisition are needed to decrease the discrepancies due to contouring. The treatment must, as far as possible, be delivered with an empty bladder and rectum in order to ensure a good reproduction of the initially planned treatment.

[Endobronchial brachytherapy]. / Curiethérapie endobronchique.

Endobronchial brachytherapy was developed following the miniaturization of radio-active sources enabling the use of fiberoptic techniques to deliver treatment at high dose yet substantially reducing the duration of treatment. Endobronchial brachytherapy has been used in patients presenting with symptomatic obstruction of the proximal bronchial tree in association with laser therapy. The level of responses in these palliative indications is around 80 per cent. Currently, other investigations are undergoing evaluation to test the method in association with conventional treatment to determine whether brachytherapy can augment local control. In the treatment of small tumours when other conventional treatments are not possible brachytherapy employed alone has shown undoubted efficacy. However there remain numerous problems to resolve: what is the ideal protocol in terms of total dose, dose per fraction, the order of dosing and fractions? How can secondary complications to endoluminal irradiation be limited in particular for curative therapy. An answer should be found for all these questions before this technique is eventually integrated into the primary treatment regimes for bronchial cancer.

[Conservative treatment of anal canal carcinoma with external radiotherapy and interstitial brachytherapy, with or without chemotherapy: long-term results]. / Traitement conservateur des cancers du canal anal par irradiation suivie de curiethérapie interstitielle, avec ou sans chimiothérapie: résultats à long terme.

PURPOSE: A retrospective analysis of conservative treatment of anal canal cancers with external radiation therapy and interstitial brachytherapy with or without chemotherapy. PATIENTS AND METHODS: From 1986 to 1996, 69 patients were treated with external radiotherapy (40 Gy/20 fractions) and interstitial brachytherapy (20 Gy) after a mean interval of six weeks for a localized epidermoid carcinoma of the anal canal. Patients who did not complete the whole therapeutic sequence were not included. Forty-five patients received additional 5-fluorouracil- and/or mitomycin C-based chemotherapy regimen. RESULTS: Acute toxicity was acceptable. Complete response rate was 81%. Actuarial local control rate was at two and five years, 65% and 59% respectively (median follow-up: eight years). At two, five and ten years, actuarial colostomy rate was 26%, 33% and 33% respectively, and colostomy-free survival rates 61%, 47% and 37%. Overall survival at two, five and ten years was 81%, 65% and 53% respectively. Distant metastases occurred in 11 patients (16%). Prognostic factors for overall survival were performance status (PS) (79% survival at five years for patients with PS 0 versus 50% for patients with PS 1-3, P = 0.04) and tumor stage (80% at five years for T1-T2 versus 53% for T3-T4, P = 0.03). Overall treatment time less than 12 weeks and time interval between external radiotherapy and brachytherapy inferior than six weeks were associated with a better local control (P = 0.05). In multivariate analysis, these prognostic factors were not significant. CONCLUSION: These results confirm the efficacy of external radiotherapy and brachytherapy in the treatment of small anal canal cancers, and point out the need for improving treatment outcome of larger tumors.

[Conservative treatment of bladder cancers with radiotherapy and concurrent chemotherapy: results and perspectives]. / Traitement conservateur des cancers de vessie par radiothérapie et chimiothérapie concomitante: résultats et perspectives.

Therapeutic strategies for muscle invasive bladder cancer are currently evolving. Transurethral surgery followed by concurrent chemotherapy and radiotherapy is the best treatment for patients not suitable for radical cystectomy. This conservative approach may be proposed for operable patients with similar survival than after cystectomy. Intermediate evaluation of response is necessary, as response is the more discriminant prognostic factor for local control. Non responders would be assigned for immediate cystectomy. Morbidity and results of salvage cystectomy are poorly evaluated and probably depending from time from initial treatment and dose of radiation.

[Treatment of infiltrating cancer of the bladder with cisplatin, fluorouracil, and concurrent radiotherapy: results of a pilot study]. / Traitement des cancers infiltrants de vessie par cisplatine, fluoro-uracile et radiothérapie concomitante: résultats d'une étude pilote.

PURPOSE: Pilot study to assess treatment feasibility and results of a 2-drug chemotherapy (CT) regimen administered concurrently with radiotherapy (RT) for muscle-invasive bladder cancer. MATERIALS AND METHODS: Fourty-six patients were included into a prospective study from December 1992 to April 1996. The median age was 66 years. Thirty-seven percent of the patients had T3B-T4 tumors, and 46% had benefited from prior macroscopically complete transurethral resection (TUR). Pelvic irradiation consisted of 50.4 Gy in 28 fractions over 39 days. Concurrent CT consisting of cisplatin (80 mg/m2/d1) and 5-fluorouracil (800 mg/m2/d2 to 5) by continuous infusions (5-FU) was delivered during the first and fifth weeks of radiation therapy. Twenty-three patients received two additional courses of adjuvant CT with cisplatin, methotrexate and vinblastin (MCV). RESULTS: The median follow-up was 38 months. The feasibility of concurrent CT-RT was excellent: 96% of the patients completed radiotherapy and 100% of them received the two courses of P-FU. The acute toxicity was mild: no hematological toxicity or renal toxicity over grade II, 4 cases of bowel or rectal reversible grade III toxicity and 2 cases of reversible grade III cystitis. A complete response was achieved in 30 out of the 42 evaluable patients (65.2%). Nine patients received an immediate salvage treatment (3 TUR, 3 additional radiotherapy and 3 cystectomies). Ten patients had local failure. Projected 3-year locoregional control was 49% for the 46 patients. Projected overall 3-year survival was 53%. Functional results were good for disease-free patients with preserved bladder: 1 grade I, 3 grade II, and no grade III cystitis. CONCLUSION: Concurrent 2-drug chemoradiotherapy with cisplatin and 5-fluorouracil is feasible without major toxicity and offers a potentially curative and conservative treatment for patients with localized muscle-invasive bladder cancer.

[Results of long-term treatment of inoperable cancer of the bladder with cisplatin and concurrent irradiation: prognostic factors of local control and survival]. / Résultats à long terme du traitement des cancers de vessie inopérables par cisplatine et irradiation concomitante: facteurs pronostiques du contrôle local et de la survie.

PURPOSE: Therapeutic strategies for muscle invasive bladder cancer are currently evolving. A recent European randomized study has shown that neoadjuvant chemotherapy does not improve the chance of cure or and radiotherapy would provide better results but there is a need to identify by prognostic factors patients who may benefit from such a conservative strategy. MATERIAL AND METHODS: One hundred and nine patients with localized muscle-invasive bladder cancer, who were not candidates for radical cystectomy, were treated with concomitant cisplatin and radiation therapy. Their mean age was 71. Thirty-six percent of the patients had T3B-4 tumors, and 37% had benefited from prior macroscopically complete transurethral resection (TUR). Pelvic irradiation consisted of 40 to 45 Gy and was followed by a boost to the bladder to a total dose of 55 to 60 Gy. Continuous infusion cisplatin (20 to 25 mg/m2/d for 5 days) was delivered during the second and fifth weeks of radiation therapy. RESULTS: Median follow-up was 73 months. The projected 5-year locoregional control rate was 43% for the 109 patients and 55% for the 86 patients with complete response. The projected overall 5-year survival rate was 36% for all patients and 44% for complete responders. Univariate analysis of prognostic factors was carried out for local control, and survival. The local control was statistically better in patients with good performance status, T2-3A, complete initial TUR, and in patients without hydronephrosis. In terms of overall survival, four factors were significant: the performance status, T-stage, absence of hydronephrosis, and complete response. By multivariate analysis, performance status, hydronephrosis and T-stage were significant factors for local control, while T-stage and complete response were the strongest determinants for survival. CONCLUSION: Concurrent cisplatin and radiation therapy is a potentially locally curative treatment for 43% of patients with muscle-invasive bladder cancer not candidates for radical surgery. Clinical T-stage and hydronephrosis have a significant and independent prognostic value on local control but appears not discriminant enough to select patients for conservative treatment.

[Preoperative concurrent radiochemotherapy for cancer of the rectum]. / Radiochimiothérapie concomitante préopératoire pour cancer du rectum.

PURPOSE: To evaluate retrospectively treatment-related morbidity of concurrent radiotherapy and chemotherapy for rectal cancer. PATIENTS AND METHODS: Between 1992 and 1995, 38 patients (median age: 60) were treated for locally advanced resectable rectal cancer. Median dose of radiotherapy was 45 Gy/25 fractions/5 weeks. Chemotherapy consisted of two courses of 5-fluorouracil and leucovorin administered during the first and the fifth weeks of radiotherapy. Median dose of 5-fluorouracil was 350 mg/m2/day, and median dose of leucovorin was 20 mg/m2/day, day 1 to day 5. Surgery was performed 5 weeks after completion of radiotherapy. RESULTS: Before surgery, one patient died of febrile neutropenia and sepsis after two cycles of chemotherapy and 45 Gy. Main pre-operative grade 3-4 toxicities were respectively: neutropenia: 3%; nausea/vomiting: 3%; diarrhea: 3%; proctitis: 5%; radiation dermatitis: 8%. Twenty-six patients underwent a low anterior resection and 11 an abdomino-perineal resection. A temporary colostomy was performed in 12 patients. Pathologic complete response rate was 27%. There was one post-operative death due to thromboembolic disease. Major post-operative grade 3-4 complications were: pelvic infection: 14%; abdominal infection: 5%; perineal sepsis: 8%; anastomotic dehiscence: 8%; cardiac failure: 5%. Delayed perineal wound healing was observed in six patients. No significant prognosic factor of post-operative complications has been observed. Median duration of hospitalization was 22 days. With a median follow-up of 24 months, 2-year overall and disease-free survival rates were 82 and 64%. CONCLUSION: Tolerance of preoperative concurrent chemoradiotherapy was acceptable. Ongoing controlled studies will assess the impact of this combined treatment on survival.

High dose rate endobronchial brachytherapy: results and complications in 189 patients.

The purpose of this study was to determine the benefit of high dose rate endobronchial brachytherapy in the treatment of obstructive lung cancer. Between September 1990 and March 1995, 189 patients with bronchogenic carcinoma were treated with high dose rate endobronchial brachytherapy. Most patients (69.3%) had received prior treatment and presented with symptomatic bronchial obstruction due to either recurrent or residual endobronchial disease. A small group (12%) was medically unfit for either surgical resection or thoracic radiotherapy and benefited from endobronchial brachytherapy alone for small endobronchial tumours. The remainder of the patients had not been treated previously and endobronchial brachytherapy was performed for life-threatening symptoms requiring emergency obstruction relief before other therapy. Treatment was performed weekly and consisted of three to four 8 to 10 Gy fractions at a radius of 10 mm from the centre of the source. Major symptomatic relief was obtained for haemoptysis (74%), dyspnoea (54%), and cough (54%). Complete endoscopic response was observed in 54% of cases. Median survival was 7 months for the entire group. For small, strictly endobronchial tumours, complete response rate was 96%, median survival 17 months, and 30 month survival 46%, with a plateau starting at 18 months. Grade 3 to 4 toxicities occurred at a rate of 17% and included massive haemoptysis (n=13), bronchial stenosis (n=12), soft tissue necrosis (n=8), and bronchial fistula (n=3). By univariate analysis, no factor was found to be predictive of late pulmonary toxicity. The present study confirms the usefulness of endobronchial brachytherapy in alleviating symptoms caused by endobronchial recurrence of bronchogenic carcinoma. In addition, this therapy can be tried with curative intent in patients who present with small endobronchial tumours and are not candidates for other forms of therapy.