Modified fractionated radiotherapy in head and neck squamous cell carcinoma (HNSCC) & re-irradiation in recurrent head and neck carcinomas.
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Carcinoma, Squamous Cell↗
Biomedical subjects
F Eschwège
Publications and source records attributed to F Eschwège.
[Hyperplasia of the arterial intima due to smooth muscle cell proliferation. Current data, experimental treatments and perspectives].
Restenosis after vascular surgery using bypasses or endovascular techniques for dilatation or recanalisation remains the major Achilles' heel for these techniques. The progressive decrease of vessel lumen in an anastomose leading to graft failure or after arterial transluminal angioplasty is due to a complex process: intimal hyperplasia. This process can be compared to an hypertrophic healing into the intimal layer, reducing the lumen of the vessel. This process appears shortly after surgery or dilatation, between the 3rd and the 18th month. Mechanisms leading to this process are particularly complex, involving several cells and many regulatory processes still unclear. Smooth muscle cells are the main actor by their ability to proliferate and to secrete matrix into the media layer but stimulation and control of this process appear nevertheless complicated. The present review focuses on the pathophysiology of intimal hyperplasia, on different cells acting and on their regulation. Also, we reviewed the experimental and clinical trials evaluating approaches to the prevention of intimal hyperplasia in arteries.
Cell Adhesion↗
[Localized cancer of the prostate. What to tell the patient?].
Answering the question from patients with adenocarcinoma of the prostate is always difficult; choice of radiation therapy (versus prostatectomy), indications of brachytherapy frequency and severity of acute and late effects as rate of survival, local control, are among the most frequent inquiries. A part of the answers are not evident of due lack, consensus and the physicians need to speak honestly and give the most appropriate responses without improving anxiety and fears of the patient.
Adenocarcinoma↗
[Influence of thermoplastic masks on the absorbed skin dose for head and neck tumor radiotherapy].
The influence of thermoplastic masks used in clinical routine for patient immobilization in head and neck radiotherapy treatment on the absorbed skin dose has been investigated at Gustave-Roussy Institute. The measurements were performed in 60Co gamma-rays, 4 and 6MV X-rays and in 8 and 10MeV electron beams. Initially, the measurements were performed with thermoluminescent dosimeters (LiF) and a NACP chamber on a polystyrene phantom in order to study the influence of physical parameters (distance, field size, energy...) on first millimeters depth variation dose. The study was completed with in vivo measurements on 14 patients using various dosimeters (thermoluminescent detectors, diodes) in order to assess the increase of dose on first millimeters depth and to verify the delivered dose during treatment sessions (quality control). In treatment conditions, masks lead to an important increase of dose on the first millimeter in 60Co gamma-rays beams (dose value normalized to maximum of dose increase from 57.1% to 77.7% for 0.5 mm-water depth and from 78.5% to 88% for 1 mm-water depth); its contribution is less important in 4 and 6 MV X-rays beams (dose value normalized to maximum of dose increase from 49.5% to 63.2% for 0.5 mm-water depth and from 59% to 70.1% for 1 mm-water depth). Concerning 8 and 10 MeV electron beams, the normalized dose value increase respectively from 78.4% to 81.7% and from 82.2% to 86.1% for 0.5 mm-water depth. In vivo dosimetry enabled the quality control of delivered dose during treatment. Measured dose is in agreement within +/- 5% with the prescribed dose for 92.3% of cases. In routine, in vivo dosimetry allowed to quantify the increase of skin dose induced by thermoplastic masks for various energies of photon and electron beams as well as quality control.
Head and Neck Neoplasms↗
[Method of radiotherapy planning for head and neck tumors using simulated CT images and radiographic data, developed at the Gustave Roussy Institute].
The paper deals with the recent improvements introduced in the most usual method applied in the Institut Gustave Roussy radiotherapy department for obtaining the anatomical data of patients treated for head and neck tumors. For each of these patients, five to seven transverses slices and a lateral radiographic film are taken from a Mecaserto simulator-CT. The anatomical representation of the patient sagittal plane is carried out from the digitalisation of the radiographic film on a Vidar Vxr-12 Plus film scanner and integrated into the Dosigray dose calculation programme in order to be used as a support for the laying out of the dose distribution in reference to the treatment. The sagittal anatomical representation obtained from the radiographic film digitalisation is compared with the one resulting from the interpolation between a limited number of irregularly-spaced transverse slices taken on the simulator-CT. The method using the simulator-scanner transverse slices and the radiographic film digitalisation represents an interesting alternative for obtaining an anatomy simulation representative of the patient in hospitals where a scanner is not available full-time for the needs of the radiotherapy process.
Cancer Care Facilities↗
[Carcinoma of the nasopharynx. Clinical aspects, indications and results of external radiotherapy and brachytherapy. State of the art in 2001].
Nasopharynx carcinomas (NPC) are a very special head and neck cancer, in term of epidemiology, clinic and pathology. Endemic disease in South East Asia, undifferentiated nasopharynx carcinoma are very frequent CT scan and NMR allow a better knowledge of the modalities of the clinical presentation. Prognostic factors include local and regional extension. NPC is a wellknown radiosensitive disease with a dose-response curve well established. Modern imaging modalities and modification of the ballistic explain the amelioration of the local control and the diminution of therapeutic sequellae. Brachytherapy is an interesting modalities for the boost and the treatment of recurrent disease. The exact place of 3 D CRT and IMRT is not yet known as modifications of fractionation. Local control for T1T2 tumor is excellent but is related to clinical extension (cranial and neurologic involvement) and nodal extension (supra clavicular N3) and show the interest of combined chemo-radiotherapy protocols.
Antineoplastic Combined Chemotherapy Protocols↗
Conformal radiotherapy and intensity-modulated radiotherapy--clinical data.
Conformal radiotherapy (CRT) is based on three hypotheses: (i) a higher rate of local control can improve the survival rate; (ii) dose escalation can increase tumor control; and (iii) CRT allows the delivery of higher doses by decreasing the incidence of late effects. These postulates are now supported by several data. Three-dimensional conformal radiotherapy (3D-CRT) has markedly progressed since its introduction two decades ago. However, there are situations for which 3D-CRT cannot produce a satisfactory treatment plan because of complex target volume shapes or the close proximity of sensitive normal tissues. This is why intensity-modulated radiation therapy (IMRT) was introduced. Its aim is to overcome the limitations of 3D-CRT by adding modulators of beam intensity to beam shaping. IMRT can achieve nearly any dose distribution; however, the role of the planner remains crucial. CRT has been investigated mainly for prostate cancers and head and neck cancers. By and large, the clinical data, although still limited, seem to confirm the advantages of this type of radiotherapy. Dose escalation in prostate cancers improves the local control rate without increasing late effects and for this cancer site IMRT appears to be a significant advance over conventional 3D-CRT. In head and neck cancers the clinical data are still scarce but encouraging. CRT should be investigated in breast cancers with the aim of reducing the incidence of late effects. The available data underline the great potential for major progress in 3D-CRT and IMRT. The techniques are still costly and time consuming, nevertheless they merit investigation since their cost should decrease. Efforts should be concentrated on the specification of robust optimization criteria, taking into account clinical and radiobiological data.
Dose Fractionation, Radiation↗
[Carcinoma of the nasopharynx].
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Antineoplastic Agents↗
Second malignant neoplasms after a first cancer in childhood: temporal pattern of risk according to type of treatment.
The variation in the risk of solid second malignant neoplasms (SMN) with time since first cancer during childhood has been previously reported. However, no study has been performed that controls for the distribution of radiation dose and the aggressiveness of past chemotherapy, which could be responsible for the observed temporal variation of the risk. The purpose of this study was to investigate the influence of the treatment on the long-term pattern of the incidence of solid SMN after a first cancer in childhood. We studied a cohort of 4400 patients from eight centres in France and the UK. Patients had to be alive 3 years or more after a first cancer treated before the age of 17 years and before the end of 1985. For each patient in the cohort, the complete clinical, chemotherapy and radiotherapy history was recorded. For each patient who had received external radiotherapy, the dose of radiation received by 151 sites of the body were estimated. After a mean follow-up of 15 years, 113 children developed a solid SMN, compared to 12.3 expected from general population rates. A similar distribution pattern was observed among the 1045 patients treated with radiotherapy alone and the 2064 patients treated with radiotherapy plus chemotherapy; the relative risk, but not the excess absolute risk, of solid SMN decreased with time after first treatment; the excess absolute risk increased during a period of at least 30 years after the first cancer. This pattern remained after controlling for chemotherapy and for the average dose of radiation to the major sites of SMN. It also remained when excluding patients with a first cancer type or an associated syndrome known to predispose to SMN. When compared with radiotherapy alone, the addition of chemotherapy increases the risk of solid SMN after a first cancer in childhood, but does not significantly modify the variation of this risk during the time after the first cancer.
Age of Onset↗
Radiation dose, chemotherapy and risk of osteosarcoma after solid tumours during childhood.
Osteosarcoma is the most frequent second primary cancer occurring during the first 20 years following treatment for a solid cancer in childhood. Using a cohort study of children treated for a solid cancer, we investigated the incidence and etiology of osteosarcoma as a second malignant neoplasm after childhood cancer in a cohort and a case-control study. We analysed the relationship between the local dose of radiation and the risk of osteosarcoma, taking into account chemotherapy received. A cohort study of 4,400 3-year survivors of a first solid cancer during childhood diagnosed in France or the United Kingdom, between 1942 and 1986, revealed 32 subsequent osteosarcomas. In a nested case-control study, we matched 32 cases and 160 controls for sex, type of first cancer, age at first cancer and the duration of follow-up. Parameters studied were the incidence of osteosarcoma, the cumulative local dose of irradiation and the cumulative dose of chemotherapy received by cases and controls. The risk of a osteosarcoma was found to be a linear function of the local dose of radiation (excess relative risk per gray=1.8), and was found to increase with the number of moles of electrophilic agents per square meter but not with other drugs. No interaction was noted between radiotherapy and chemotherapy. Bilateral retinoblastoma, Ewing's sarcoma and soft tissue sarcoma were found to render patients susceptible to a higher risk of developing an osteosarcoma as a second malignant neoplasm. We recommend long-term surveillance of patients who were treated during childhood for bilateral retinoblastoma, Ewing's sarcoma, soft tissue sarcoma, as well as other first cancer treated with radiotherapy plus high doses of chemotherapy, without focusing exclusively on the radiation field.
Adolescent↗
[Chemoradiotherapy of carcinomas of the upper aerodigestive tract].
The objective of this study was to review randomized trials which evaluated the effect of the radio-chemotherapy in head and neck carcinoma, and which compared radiotherapy alone vs the same local treatment plus chemotherapy. Over 40 such randomized trials have been performed, which generally showed no statistical difference between both arms. However few trials showed a benefit which is almost always in favor of the CT arm. Indeed, some trials of concomitant chemoradiotherapy have shown a statistically significant benefit in favor of the combined treatment. On the contrary, neoadjuvant chemotherapy generally leads to no detectable benefit compared to radiotherapy alone. These results have been reinforced by those of four randomized trials comparing neoadjuvant chemoradiotherapy and the same chemotherapy but given concomitantly with radiotherapy. The global effect of chemotherapy on survival of patients with head & neck squamous cell carcinoma has been recently evaluated by a meta-analysis based on individual patient data which included more than 10,000 patients from 63 randomized trials. The absolute survival rate benefit at 5 years is 4%, but is more pronounced in the concomitant combinations (8% at 5 years). In tumors classified as "T3" of the pharyngo-larynx, neoadjuvant chemotherapy followed by radiotherapy in good responders can avoid a total laryngectomy without significantly compromised survival. In the nasopharynx carcinoma, a few randomized studies have been performed, suggesting a benefit in favor of chemoradiotherapy. Finally, future randomized trials will determine what are the optimal chemoradiotherapy schedules, as well as determining what is the best radiotherapy (accelerated, hyperfractionated) to use in combination with chemotherapy.
Antineoplastic Agents↗
Results of a European randomized trial of Etanidazole combined with radiotherapy in head and neck carcinomas.
PURPOSE: The aim of the study was to evaluate the efficacy and toxicity of Etanidazole, a hypoxic cell sensitizer, combined with radiotherapy in the treatment of head and neck squamous cell carcinoma. METHODS AND MATERIALS: A total of 374 patients from 27 European centers were included in this trial between 1987 and 1990. Treatment was either conventional radiotherapy alone (between 66 Gy in 33 fractions and 74 Gy in 37 fractions, 5 fractions per week), or the same radiotherapy dose plus Etanidazole 2 g/m2, three times weekly for 17 doses. A minimization procedure, balancing for center, site, and T stage (T1-T3 vs. T4) was used for randomization. RESULTS: Among the 187 patients in the Etanidazole group, 82% received at least 14 doses of the drug. Compliance to the radiotherapy protocol was 92% in the Etanidazole group and 88% in the control group; the main cause of deviation was acute toxicity, which was observed at an equal rate in the two treatment groups. Fifty-two cases of Grade 1 to 3 peripheral neuropathy were observed in the Etanidazole group vs. 5 cases, all of Grade 1, in the control group (p < 0.001). The 2-year actuarial loco-regional control rates were 53% in the Etanidazole group and 53% in the control group (p = 0.93), and the overall 2-year survival rates were 54% in each group (p = 0.99). CONCLUSION: Adding Etanidazole to conventional radiotherapy did not afford any benefit for patients with head and neck carcinoma. This study failed to confirm the hypothesis of a benefit for patients with N0-N1 disease, which had been suggested by the results of a previous study (10).
Adult↗
Radiation and genetic factors in the risk of second malignant neoplasms after a first cancer in childhood.
BACKGROUND: Radiotherapy and chemotherapy are associated with an increased risk of second malignant neoplasm (SMN). An association between SMN and familial aggregation has also been shown. The aim of this study was to investigate the role of familial factors in the risk of SMN and their potential interaction with the effect of treatment. METHODS: We devised a case-control study of 25 children with SMN (cases) and 96 children with no SMN after a cancer treatment (controls), taken from a cohort of 649 children treated at our institution between 1953 and 1985. A complete family history was obtained for patients and controls and a familial index defined to evaluate the degree of familial aggregation. The radiation dose given at 151 sites in the body was estimated for each radiotherapy course for each child. FINDINGS: Among family members of the 25 SMN cases, there were ten with early-onset (< or = 45 years) cancer, compared with eight among relatives of the 96 controls. Compared with patients who had no family history of early-onset cancer, those with one or more affected family members had an odds ratio for SMN of 4.7 (95% CI 1.3-17.1; p = 0.02). Adjustment for local radiation dose and exclusion of patients known to be predisposed to SMN (carriers of p53 mutation and those with Recklinghausen's disease) did not affect this risk substantially. INTERPRETATION: Both genetic factors and exposure to ionising radiation have independent effects on the risk of SMN. Follow-up of children treated for cancer should be especially vigilant when there is a family history of early-onset cancer.
Adolescent↗
[Therapeutic approaches of adenocarcinoma of the exocrine pancreas. Trends in 1997].
The prognosis for adenocarcinoma of the pancreas remains poor. Besides surgical treatment of operable localised tumours, many questions are raised: what is the role of adjuvant therapies, chemo-radiotherapy, pre-operative or post-operative combinations, and what is the role of radiotherapy or chemo-radiotherapy during surgery? In the case of inoperable tumours, there is no consensus on the role and the value of various protocols whose toxicity is generally high. Improvements in treatment must come from a better understanding of the role of various prognostic factors (biological markers in particular).
Adenocarcinoma↗
Intratumoral oxygen tension in metastatic melanoma.
Tumour hypoxia can lead to a decrease in the biological effectiveness of radiation and alkylating agents. Few data are available on oxygen tension (PO2) in melanoma. In 20 patients with past history of melanoma, PO2 was evaluated in normal tissues and suspected metastatic lesions (nodes and skin metastases). Oxygen tension was measured using a needle probe technique (KIMOC-6650 histograph, Eppendorf, Germany), the day before the surgical removal of the suspected metastatic lesion. Histological confirmation of the malignant origin of the removed lesion was obtained in 18 cases. In two cases invasion by the known melanoma was not seen histologically. The median PO2 for normal tissues was 40.5 mmHg. For tumours, the median PO2 was 11.6 mmHg, and it was 17.1 mmHg in nodes and 6.7 mmHg in skin metastases. Very low values (< 2 mmHg) accounted for 20% of the recorded values in nodes and 15% in skin metastases. When analysed according to the node size (< or > or = 3 cm in diameter), the median PO2 was 10.4 mmHg in large nodes (six patients) and 53.3 mmHg in small nodes (six patients). For the two non-tumoral lesions, the median PO2 values were 20.9 and 25.1 mmHg, with no values below 10 mmHg. Thus a decrease in PO2 values, probably corresponding to tumour hypoxia, was found in most of the metastatic tumours when compared with normal tissues. The prognostic value of these PO2 measurements in melanoma remains to be demonstrated in the tumour response to radiotherapy or alkylating agents. However, tumour hypoxia can already be investigated as a target for new treatment modalities in metastatic melanoma.
Adult↗
Advanced carcinoma of the larynx: results of surgery and radiotherapy without induction chemotherapy (1980-1985): a multivariate analysis.
PURPOSE: Induction chemotherapy has been proposed in the case of advanced laryngeal cancer in order to preserve laryngeal function in those patients who are complete responders. To clarify the treatment policies, a retrospective multicentric analysis of 116 patients with advanced carcinoma of the larynx treated by radical surgery and postoperative radiotherapy was carried out in order to evaluate prognostic factors for local control and survival. METHODS AND MATERIALS: Between 1980 and 1985, 116 patients with Stage III squamous cell carcinoma of the larynx underwent radical surgery and postoperative radiotherapy with a curative intent. Treatments were very homogenous, and doses delivered were in the range of 50-65 Gy according to nodal involvement and surgical margins status. RESULTS: The local recurrence rate and the local disease-free survival rate at 5 years were 22.5% and 76.3%, respectively. Actuarial survival at 5 years was 68.3% with 44 patients still alive with no evidence of disease (NED) with more than 5 years follow-up. For both overall survival and relapse-free survival, cervical node involvement with capsular rupture was found to be the only significant adverse pronostic factor in univariate and multivariate analysis. No other parameter was predictive either for local recurrence or for survival. CONCLUSIONS: Local prognosis and survival depend largely on nodal involvement and capsular rupture while increasing doses of radiation strategy is likely to reduce the risk of local and nodal recurrence. Preservation of functional larynx is certainly an important goal to achieve when treating advanced carcinoma of the larynx, provided that local failure rate and survival be similar. In the unique randomized study previously published in the literature comparing radical surgery and postoperative radiotherapy to induction chemotherapy and radiotherapy, the local-regional failure rate was drastically increased in the chemotherapy arm. Other results from well-designed controlled studies are awaited before recommending systematic induction chemotherapy and larynx preservation in complete responders. On the other hand, testing synchronous or alternated chemotherapy vs. induction chemotherapy may address the pending questions about the optimal treatment of advanced laryngeal carcinoma.
Adult↗
CT and MR imaging of squamous cell carcinoma of the tongue and floor of the mouth.
Because contemporary treatment of oral cavity cancer involves procedures that spare the tongue and mandible, an adequate assessment of the oral cavity is essential for appropriate surgical and radiation therapy planning. Computed tomography (CT) and magnetic resonance (MR) imaging, which allow differentiation between soft tissues, are valuable tools for assessing this complex region. Their main advantage resides in their capacity to show at best the normal anatomy and the exact extent of a low-lying tumor. For display of soft tissues and tumor, MR imaging, being a multiplanar and multicontrast technique, is superior to CT. Nonenhanced T1-weighted MR imaging is better for defining the exact extent of medullary bone invasion, which appears as a low-signal-intensity area within hyperintense medullary fat. CT is optimal in detection of cortical bone invasion, which appears as an interruption or erosion of the peripheral hyperattenuating rim. Thus, in cancer of the tongue, MR imaging should be performed first. If tumor extension to the mandible is suspected (due to clinical or MR imaging findings), CT should be added. In cancer of the floor of the mouth, both MR imaging and CT should be performed in the initial work-up, especially in those cases in which there is a clinical doubt about mandibular extension of disease. The main drawback of both modalities is their lack of specificity; other methods are needed to discriminate between tumors and inflammatory or infectious diseases, particularly in the mandible. However, once the diagnosis has been confirmed histologically, treatment can be chosen based on complementary information obtained from CT and MR imaging.
Carcinoma, Squamous Cell↗
[Perioperative chemotherapy of squamous cell carcinoma of the hypopharynx].
The aim of this prospective study was to decrease the rate of locoregional recurrence (LRR) and distant metastasis (DM) with a multi-modality approach in hypopharyngeal squamous cell carcinoma (HSCC). Patients presenting with squamous cell carcinoma of the pyriform sinus, epilarynx or postcricoid area with indication of pharyngolaryngectomy, without previous treatment, distant metastasis, multiple primaries or general contraindications for surgery and chemotherapy were included in the study. Patients received three consecutive cycles of chemotherapy (CDDP cisplatinium 100 mg/m2 D1, 5-FU 1 g/m2 D1 to D5) before surgery, then two postoperative courses of the same chemotherapy at day 10 and 31 after surgery. Postoperative radiotherapy was initiated at day 50. Between 1986 and 1989, of 198 patients with HSCC, 60 were included in this study. Tumour response of the induction chemotherapy was: no response (NR): 22; partial response (PR): 25; complete response (CR): 11; non evaluable: 2. Forty-seven patients underwent surgery. Only two patients had no viable tumour in the surgical specimen and two others only keratin debris. Of 39 patients in which protocol treatment was respected, 4 LRR, 4 LRR + DM, 8 DM, three second head and neck primaries, and one acute myeloblastic leukemia were observed. Results were compared with those of historical series, with the same mean delay of follow up. The rate of survival at 2 and 5 years was 78% and 42% in the present series, while it was 77% and 33% in the control group, respectively (NS).
Actuarial Analysis↗