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R Dendale

Publications and source records attributed to R Dendale.

At least 19 recordsLinked to original sources
PubMed2006

Proton beam therapy for iris melanomas.

AIMS: To describe the results in terms of local control, eye preservation and systemic evolution of iris melanomas treated by proton beam irradiation. METHODS: Retrospective review of the charts of patients with iris melanoma treated by proton beam therapy between April 1998 and September 2002. Ciliary body melanomas with iris involvement or tumours with extrascleral invasion were excluded. Treatment consisted of 60 Gy of proton beam irradiation delivered in four fractions to the tumour volume. RESULTS: A total of 21 patients were treated, median follow-up of 33 months (8-72 months). 15 patients presented a lesion with documented growth. The median clinical diameter was 5 mm (2-8 mm), the median ultrasound diameter 4.8 mm (2-7.7 mm) The patients were 6% T1, 57.1% T2, and 14.3% T3 all N0M0. The iridocorneal angle was invaded by the tumour in 71.4% of patients. At the end of follow-up, all patients were alive with no proven metastatic disease except one patient with suspicious liver lesions. None of the patients showed tumour progression or ocular relapse. The tumour response at 2 years was a flat lesion for 6.3% of cases, partial regression in 75% and stable in 18.8%. None of the patients required secondary enucleation. The main complication was cataract (45% within 24 months of treatment). Raised intraocular pressure was observed in 15% of patients but no neovascular glaucoma. CONCLUSIONS: Proton beam therapy shows potential utility for selected cases of localised iris melanomas allowing excellent local tumour control and eye preservation. Further follow-up on larger series is needed to confirm these results.

Adolescent↗
PubMed2006

Combined proton beam radiotherapy and transpupillary thermotherapy for large uveal melanomas: a randomized study of 151 patients.

INTRODUCTION: Exudation from the tumour scar and glaucoma can be major problems after proton beam irradiation of uveal melanoma and can sometimes lead to secondary enucleation. We conducted a randomized study to determine whether systematic transpupillary thermotherapy (TTT) after proton beam radiotherapy could have a beneficial effect. PATIENTS AND METHOD: Between February 1999 and April 2003, all the patients treated by proton beam radiotherapy for uveal melanomas >/=7 mm thick or >/=15 mm in diameter were included in this study after giving their informed consent. One half of the patients received proton beam radiotherapy alone (60 Gy in 4 fractions) and the other half received the same dose of proton beam radiotherapy followed by TTT at 1, 6 and 12 months. All the information concerning the initial tumour parameters, treatments and follow-up was recorded and a statistical analysis was performed. RESULTS: We randomized 151 patients. The median follow-up was 38 months. The 2 groups of patients were similar in terms of age, gender and tumour characteristics. The patients treated with TTT showed a greater reduction of tumour thickness (p = 0.06), less retinal detachment at the latest follow-up (p = 0.14) and a lower secondary enucleation rate (p = 0.02). DISCUSSION: The present study is the first randomized analysis to demonstrate a significant decrease in the secondary enucleation rate in patients treated with TTT after proton beam radiotherapy. Further studies should be performed to determine whether TTT could be beneficial to smaller tumours and to define its optimal dose.

Adult↗
PubMed2006

Breast radiotherapy in women with pectus excavatum (funnel chest): is the lateral decubitus technique an answer? A dosimetric study.

Breast radiotherapy is a technical challenge in women with pectus excavatum. We aim to assess isocentric lateral decubitus (ILD) technique as a means to irradiate breasts for patients with pectus excavatum. Four women presenting with left-sided breast cancers and found to have pectus excavatum were offered breast-conserving treatments. Post-operative breast radiotherapy was indicated (50 Gy) in two patients, with an additional boost to the tumour bed (16 Gy). Both ILD and supine techniques were simulated. We report the dosimetric comparison of these techniques and the acute skin toxicity of ILD radiotherapy. ILD permitted the same breast dose-homogeneity as the supine technique while decreasing breast thickness by 4.5-6.8 cm. The width of lung and/or heart receiving > 20 Gy ranged between 2.1 cm and 4.3 cm with the supine technique and between 0.5 cm and 1.1 cm with ILD. The estimated percentage of ipsilateral lung receiving > 20 Gy ranged from 21% to 34% with the supine technique and from 0% to 5% with ILD. Acute skin toxicity was scored 1 for all patients at completion of ILD radiotherapy. ILD is an effective breast radiotherapy technique for patients with pectus excavatum that preserves the underlying heart and lung from unnecessary toxicity.

Adult↗
PubMed2006

[Prognostic factors for malignant uveal melanoma. Retrospective study on 2,241 patients and recent contribution of monosomy-3 research].

INTRODUCTION: We conducted a retrospective study on the clinical factors influencing the local and general prognosis of patients treated for uveal melanoma with a preliminary analysis of the prognostic value of monosomy 3. PATIENTS: and method: The patients sent to Curie Institute for uveal melanoma have a complete initial clinical evaluation, conservative management by radiotherapy or enucleation, and local and general long-term follow-up. Over the last 5 years, the status of chromosome 3 has been assessed by FISH in the tumors of enucleated patients. Findings concerning the initial workup, treatment, and follow-up are recorded prospectively. We conducted a retrospective study with multivariate analysis of the clinical factors influencing local recurrence, ocular conservation metastasis, and survival and studied the effect of monosomy 3. RESULTS: A total of 2241 patients were registered with a median follow-up of 72 months. Of these patients, 92.8% had conservative management with iodine 125 brachytherapy or proton beam therapy and 7.2% of the patients had enucleation (n=160). Tumors from 120 patients were studied for the status of chromosome 3 by FISH. The overall survival rate was 76.3% and the metastatic rate was 19.5%. The clinical factors influencing survival were the size and location of the tumor, age of the patient, gender, and initial treatment. The factors influencing the metastatic risk were the same plus retinal detachment and local recurrence. Monosomy 3 was a significant risk factor for metastatic disease. DISCUSSION: This study found the usual risk factors with the difference that location on the equator seems to be of worse prognosis than ciliary body involvement for survival and metastasis. In addition, the initial retinal detachment appears to be a risk factor for local recurrence and metastasis. At present, the evaluation of chromosome 3 is available for enucleated tumors but it could probably be done on needle biopsy performed during conservative management as well. CONCLUSION: This study confirms previous results on the prognostic factors of uveal melanoma and on the value of monosomy 3. The increasingly precise identification of a group of high-risk patients should allow us to propose adjuvant therapy and to adapt follow-up.

Disease-Free Survival↗
PubMed2005

[Radiation-induced sarcomas after breast cancer: experience of Institute Curie and review of literature].

Adjuvant radiotherapy to the breast plays a significant role in preventing local failure in women treated for early stage breast cancer. This fact is supported by multiple clinical trials demonstrating that adjuvant radiotherapy decreases the risk of local recurrence and increases the rate of breast preservation, and actually the rules of adjuvant breast irradiation are clearly established. Sarcomas are a rare but recognized complication of radiation therapy for breast carcinoma, and are associated with poor prognosis. The first case of a bone sarcoma after radiation therapy of breast cancer was described by Beck in 1922. In 1948, Cahan et al. defined the criteria for diagnosis of radiation-induced sarcoma. Since then, some studies have reported the incidence of radiation-induced sarcoma after radiotherapy for different cancers. This article reports and discusses the incidence, management and treatment outcome of radiation-induced sarcomas occurring after radiotherapy for breast cancer in our institute. The incidence, histology, latency of appearance, genesis, their treatment and the prognostic factors of these rare tumors are discussed and the literature is reviewed.

Adult↗
PubMed2005

[Radiotherapy for breast cancer: respiratory and set-up uncertainties].

Adjuvant Radiotherapy has been shown to significantly reduce locoregional recurrence but this advantage is associated with increased cardiovascular and pulmonary morbidities. All uncertainties inherent to conformal radiation therapy must be identified in order to increase the precision of treatment; misestimation of these uncertainties increases the potential risk of geometrical misses with, as a consequence, underdosage of the tumor and/or overdosage of healthy tissues. Geometric uncertainties due to respiratory movements or set-up errors are well known. Two strategies have been proposed to limit their effect: quantification of these uncertainties, which are then taken into account in the final calculation of safety margins and/or reduction of respiratory and set-up uncertainties by an efficient immobilization or gating systems. Measured on portal films with two tangential fields, CLD (central lung distance), defined as the distance between the deep field edge and the interior chest wall at the central axis, seems to be the best predictor of set-up uncertainties. Using CLD, estimated mean set-up errors from the literature are 3.8 and 3.2 mm for the systematic and random errors respectively. These depend partly on the type of immobilization device and could be reduced by the use of portal imaging systems. Furthermore, breast is mobile during respiration with motion amplitude as high as 0.8 to 10 mm in the anteroposterior direction. Respiratory gating techniques, currently on evaluation, have the potential to reduce effect of these movements. Each radiotherapy department should perform its own assessments and determine the geometric uncertainties with respect of the equipment used and its particular treatment practices. This paper is a review of the main geometric uncertainties in breast treatment, due to respiration and set-up, and solutions proposed to limit their impact.

Breast Neoplasms↗
PubMed2005

[Functional results of retinoblastoma treatment with local treatment used in isolation or associated with chemotherapy].

INTRODUCTION: Because of long-term complications of external beam radiation in retinoblastoma, a new therapeutic modality using chemotherapy and local treatments is used whenever possible. We conducted a retrospective study to evaluate visual results. PATIENTS AND METHOD: We studied visual acuity and ocular side effects in children presenting uni- or bilateral retinoblastoma in whom we were able to achieve conservative management without external beam treatment. The treatments that were used included chemotherapy, chemothermotherapy, diode laser, iodine 125 plaque brachytherapy, and cryotherapy. The initial characteristics (diameter, subretinal or vitreous seeding, and location) of each tumor, the treatments used, their results, and the visual function after age 4 years were recorded. RESULTS: We treated 429 children for retinoblastoma at the Curie Institute between October 1994 and December 2002. Two hundred twenty-seven eyes had conservative treatment without external beam. We were able to study the visual function in 102 eyes at a median age of 67 months. The median follow-up after the end of the treatment was 5 years. The mean visual acuity was 20/37 and 60% of the children had visual acuity of more than 20/40. Macular alteration was observed in 34 eyes. Statistical analysis showed that a larger tumor diameter of the retinal surface (p<0.0003) and location close to the macula (p<0.0001) were the most significant risk factors for vision loss. CONCLUSION: The visual results of the treatment of retinoblastoma by chemotherapy and local treatments is good when the tumors are not located close to the macula. Larger tumors also have a worse prognosis for vision.

Child, Preschool↗
PubMed2005

[Results of treating uveal melanoma with proton beam radiation: 10-year follow-up].

PURPOSE: We analyzed the long-term results of uveal melanoma treatment with proton beam irradiation in a series of patients with a follow-up of at least 10 years. PATIENTS AND METHODS: The patients were treated with proton beam radiation between September 1991 and December 1992. They had an initial examination including visual acuity, funduscopy, A and B scan ultrasonography of the eye, fundus photographs and fluorescein angiography. General examination included chest radiography and B scan ultrasonography of the liver. All tumors received a total dose of 60 cobalt-Gray equivalents (applied in four daily fractions) at the Orsay proton therapy center. RESULTS: A total of 167 patients were treated with a median follow-up of 116 months. Their median age was 59 years. Thirteen tumors were anterior to the equator, 76 overlapped the equator and 78 were posterior to the equator. An initial retinal detachment was present in 41 cases. The optic disk was invaded in 10 cases. The median tumor diameter was 12 mm and the median tumor thickness was 5.8 mm. The mean initial acuity was 20/50. The survival rate was 62.93% at 10 years; 72.9% of deaths resulted from metastasis. Statistically significant risk factors for death identified in the multivariate analysis were tumor diameter greater than 12 mm (p=0.0004) and age over 60 years (p=0.0001). The metastasis rate at 10 years was 31%. The liver was affected in 97.8% of these patients. Risk factors for metastasis were the anterior site of the tumor, its volume greater than 0.4 cc and the presence of retinal detachment at diagnosis. The secondary enucleation rate at 10 years was 13.23%, mainly attributable to secondary neovascular glaucoma. The local recurrence rate was 6%. The visual acuity rate in 42.1% of patients was better than 20/100 at 10 years. Visual loss was mainly due to postradiation maculopathy and neuropathy. CONCLUSION: Our study confirms the long-term results found in the literature on proton beam radiation. This therapy allows good tumor control, an excellent eye retention rate, and good final visual acuity for approximately half of the patients.

Adolescent↗
PubMed2004

125I plaque brachytherapy for anterior uveal melanomas.

PURPOSE: To describe the results of 125I plaque brachytherapy of uveal melanomas anterior to the equator in terms of local control and the associated complications while trying to identify their risk factors (patients' demographic data, ocular, and tumour characteristics). METHODS: Retrospective analysis of a series of patients treated by 125I between 1990 and 2000 in a single institution. The main outcome measures are evaluation of local tumour control and complications associated with 125I plaque brachytherapy of these melanomas. RESULTS: During the study period, 136 patients were treated for an anterior tumour. The median follow-up was 62 months. The overall 5-year survival rate was 88.3%, the 5-year metastasis rate was 4% and the local recurrence rate was 1.5%. The mean final visual acuity was 20/40. The ocular complications most frequently observed at 5 years were cataract (50.3%), maculopathy (18.3%), intraocular inflammation (19.3%), and glaucoma (10.6%). Optic neuropathy, retinal detachment, keratitis, and intravitreous haemorrhage were also described. Risk factors for worse survival were age greater than 65 years and initial tumour thickness greater than 4 mm. Risk factors for the development of cataract were age more than 65 years old, male gender, and tumour diameter of more than 10 mm. Risk factors for intraocular inflammation were tumour thickness of more than 4 mm and invasion of the ciliary body. CONCLUSIONS: The use of 125I plaque brachytherapy to treat melanomas situated anterior to the equator allows good local and systemic control with a low rate of macular and optic disc complications. The most frequent complication was cataract formation.

Adult↗
PubMed2003

[Radiotherapy in the treatment of eyelid tumors].

We describe the different radiation therapy techniques for malignant tumors of the eyelid, their results in squamous-cell and basal-cell carcinoma, their side effects, and the advantages and disadvantages compared to surgery. The most frequent indications for radiation in the management of these tumors are also reviewed.

Brachytherapy↗
PubMed2003

[Bilateral uveal melanomas. Five case reports].

PURPOSE: Uveal malignant melanoma is the most common primary intraocular tumor in adults. The occurrence of bilateral uveal melanoma is an extremely rare event, but the observed frequency is nevertheless higher than what can be attributed to chance. Possible responsible factors may include a genetic predisposition. PATIENTS AND METHODS: This retrospective study investigated the charts of patients examined from July 1988 to July 2001. For each patient, the clinical characteristics of the tumor (diameter, thickness, location), treatments, and results were noted, as were the eye involved, the presence of ocular melanocytosis, cutaneous melanoma, and second primary cancers. The information was then subjected to statistical analysis. RESULTS: Of 2 461 patients with unilateral primary uveal melanoma, five were identified as having bilateral uveal melanoma (0.2%). The expected number of cases would be less than one, hypothesizing an incidence of second melanoma identical to the incidence of a primary melanoma in the general population. The interval between the diagnosis of first and second primary uveal melanomas ranged from 0 to 6 years (median, 2 years). There was no clinical evidence of ocular melanocytosis in any of the five patients. The uveal melanoma was choroidal in three patients and affected the ciliary body or iris and choroid in two patients. DISCUSSION: The discrepancy between the estimated incidence (thought by Shammas to be one case every 18 years) and the observed incidence of bilateral primary uveal melanoma could be the result of many possible factors. An increased incidence of unilateral uveal melanoma could be a cause but in fact the incidence of uveal melanoma seems stable. Uveal melanoma may have been misdiagnosed in earlier years. The presence of a genetic predisposition to uveal melanoma is a possible explanation (suspected because of bilateral cases, familial cases and association with other primary malignancies). Ocular melanocytosis, which is described as more common in patients with bilateral uveal melanoma, was not seen in our series. CONCLUSION: Bilateral primary uveal melanoma occurs more frequently than expected. Unidentified germline mutations may be involved in pathogenesis. These cases serve as a reminder of the of the importance of careful examination of the second eye.

Aged↗
PubMed2003

[Diode laser thermotherapy and chemothermotherapy in the treatment of retinoblastoma].

INTRODUCTION: The use of transpupillary thermotherapy alone or associated with systemic chemotherapy is a therapeutic modality of ocular retinoblastoma that allows ocular preservation without external beam irradiation of the eye. We present our experience with thermotherapy in the treatment of selected cases of retinoblastoma. MATERIAL AND METHODS: This paper reports a retrospective case series of patients treated for retinoblastoma by thermotherapy or chemothermotherapy (carboplatin IV followed by thermotherapy) in a single institution from October 1994 to December 2000. Data collected include general characteristics of the treated children, tumor characteristics, and the results of the treatments on local tumor control. Transpupillar thermotherapy was delivered with a diode laser through an operating microscope. Each tumor was treated separately and laser intensity, spot size, and duration were adapted to the size of the tumor and the clinical response. Chemothermotherapy consisted in thermotherapy delivered shortly after an intravenous injection of carboplatin (560 mg/m(2)) at day 1, followed by thermotherapy alone at day 8 if the lesion was 6mm or more in diameter. This cycle was administered every 28 days. The choice between thermotherapy and chemothermotherapy depended on the initial size of the lesions. Thermotherapy was used when the lesion measured 3mm or less. Lesions measuring more than 15 mm, or associated with substantial vitreous seeding, retinal detachment, or optic nerve head involvement are not suitable for these techniques. RESULTS: During the study period, 239 children were treated in our institution and 109 of them (147 eyes, 372 tumors) could be treated conservatively without external beam radiation. The median tumor diameter at the moment of thermotherapy or chemothermotherapy was 2mm (range, 0.2-15.0mm). One hundred and ninety-four tumors were treated by chemothermotherapy and 18 by thermotherapy alone. In 75% of the cases, the treatment was administered after two courses of chemotherapy (etoposide and carboplatin). After a mean follow-up of 55 months (range, 16-89 months), tumor control was obtained in 87.1% of lesions after chemothermotherapy and 77.8% after thermotherapy. Salvage enucleation was necessary for seven lesions (seven eyes) but none in the cases where thermotherapy was used alone. No severe systemic side effects were noted. DISCUSSION: Diode laser delivers hyperthermia on the tumor bed and its use alone or in association with systemic administration of carboplatin makes it possible to preserve the eye without external beam irradiation, with few side effects and less cumulative doses of chemotherapy. CONCLUSION: Thermotherapy and chemothermotherapy provide excellent local tumor control and eye preservation in selected cases of retinoblastoma.

Antineoplastic Agents↗
PubMed2003

[Treatment of uveal melanoma with iodine 125 plaques or proton beam therapy: indications and comparison of local recurrence rates].

INTRODUCTION: This retrospective study compared the rate of local recurrence after irradiation of uveal melanoma treated with iodine 125 plaques or proton beam therapy. PATIENTS AND METHODS: Iodine 125 plaques were used to treat all uveal melanomas between the end of 1989 and 1991. Since 1991, we have used iodine plaques for small anterior tumors and proton beam for other tumors. We use a plaque with a larger diameter than the tumor diameter (2-4mm) with a dose of 90Gy at the apex. Proton beam therapy is used for all tumors at the equator or posterior to the equator not thicker than 12mm. The dose given is 60Gy cobalt equivalent in four fractions. For each patient, the initial size and location of the tumor were noted as well as the follow-up each year: the outcome for the eye (local recurrence, ocular conservation, and functional results), the occurrence of metastasis, and survival. A statistical analysis was performed. RESULTS: Between December 1989 and September 1998, 1272 patients were treated: 926 (72.8%) were treated with proton beam irradiation and 346 (27.8%) with iodine 125 plaques. The median follow-up was 5 years (60 months). For the patients treated with proton beam therapy, the mean age was 58 years, the tumor location was anterior to the equator for 3.8%, at the equator for 43.6%, and posterior to the equator for 52.6%. The mean tumor diameter was 13.4mm and the mean tumor thickness was 5.69mm. For the patients treated with iodine 125 plaques, the mean age was 61.5 years. The location of the tumor was anterior to the equator for 34.4%, at the equator for 46.5%, and posterior to the equator for 19.1%. The mean tumor diameter was 11.5mm and the mean tumor thickness was 5.12mm. The recurrence rate was 4% for the proton beam treatment and 3.75% for iodine plaques. There was no statistical difference. DISCUSSION: In the literature, the rate of local recurrence is usually higher with iodine 125 plaques than proton beam therapy. We discuss the risk factors for local recurrence after iodine 125 plaques: tumor diameter, lower dose to the tumor apex and lower dose rate, and posterior location of the tumor. We found a higher mortality rate in patients who presented local recurrence. CONCLUSION: When we use iodine 125 plaques for anterior tumors with the proper dose and dose rate to the apex of the tumor, we do not find more recurrence than with proton beam therapy.

Adolescent↗
PubMed2002

[Radiation-induced retinopathy].

Radiation retinopathy is a retinal microangiopathy, observed after irradiation of the eye. It can rarely lead to neovascular glaucoma and enucleation due to pain. It is due to a progressive retinal capillary then vascular occlusion. Total irradiation dose, dose fraction, and surface of the irradiated retina seem to be strong predictive factors for radiation retinopathy. Patients who underwent an irradiation near the eye (skull base tumors, nasal and paranasal tumors, or brain tumors) should be followed by periodic ophthalmologic examination to detect and treat when necessary the non perfusion areas.

Eye Injuries↗
PubMed2002

[Results of proton beam irradiation for treatment of choroidal melanoma].

PURPOSE: To evaluate the results of proton beam irradiation of choroidal melanomas on a large series of patients. PATIENTS AND METHODS: Retrospective analysis of a series of patients treated with proton beam irradiation between 1991 and December 1998. The data were analyzed to evaluate the local tumor control as well as the general progression and metastatic rate of the patients. Statistical analysis served to isolate risk factors for relapse or metastasis. RESULTS: We treated 1062 patients during the study period, with a median follow-up of 38 months. Local control was obtained for 97.1% of the patients. Tumors anterior to the equator were at risk for relapse. The survival rate was 92% at 2 years and 78% at 5 years. 73.1% of the 1062 patients died from metastasis, 6.1% of living patients presented with metastatic disease. The risk factors for death were the initial diameter, the age of the patient, and large tumor volume at diagnosis. Metastasis were essentially hepatic (94.6%). Risk factors for metastasis were: a large tumor volume, a lesion anterior or straddling the equator and the age of the patient. Ocular complications may induce a visual loss of 0.1 and less in 47% of the patients, due to optic nerve head and macular ischemia. 6% of the patients required secondary enucleation due to local complications (neovascular glaucoma). CONCLUSION: Proton beam irradiation of choroidal melanoma allows good tumor control and eye retention. The survival prognosis is associated with the initial volume of the tumor. The functional results may be improved and new therapeutics are needed to treat metastatic disease.

Adolescent↗
PubMed2000

[Radiotherapy of cancer of the breast. Technical problems and new approaches].

Technical problems often arise during irradiation to the breast, chest wall, and regional lymph nodes. The following are among the most frequently encountered problems: avoidance of normal tissues (heart and lungs) during chest wall, internal mammary nodes, and large breast irradiations; dose heterogeneity in large breasts; under- or overdosage at field junctions (breast medial tangent and internal mammary fields in particular). Various technical solutions have been offered: modified treatment positions, field inclinations, and conformal irradiation. Many are currently under evaluation. These new technical approaches in breast cancer irradiation require modern facilities for imaging, simulation, and dosimetry, which help to individually design treatment planning.

Breast Neoplasms↗
PubMed1997

[Radiotherapy of glioblastoma].

Glioblastoma cells appear to be inherently radioresistant and to present a significant fraction of hypoxic cells. The most significant prognostic factors to compare results achieved in several series of patients are the age, performance status and quality of surgical resection. Several randomized trials have provided evidence supporting the efficacy of radiation therapy in the treatment of glioblastoma. Prescription of a 60-Gy dose delivered according to a conventional dose-fractionation scheme (single daily fractions of 1.7 to 2 Gy five times per week) in a target volume with a 2-3 cm margin of tissue surrounding the perimeter of the contrast enhancing lesion on computerized tomography and magnetic resonance imaging is derived from observations made in several retrospective and prospective studies. Evidence of improvement in survival was observed neither in patients receiving hyperfractioned and accelerated radiotherapy, nor in patients for whom radiation sensitizers such as nitroimidazole compounds or halogenated pyrimidine analogs were associated to radiation therapy. The addition of nitrosourea to radiotherapy increases the 2-year survival rate by about 10%. Combination of full-dose external beam radiotherapy and brachytherapy or radiosurgery boost in selected patients with glioblastoma leads to an increase in the median survival, while external beam radiation alone in patients with similar prognosis does not.

Age Factors↗