Search PubMed⌕ Search

Biomedical subjects

Roberto Orecchia

Publications and source records attributed to Roberto Orecchia.

At least 55 records · Page 3Linked to original sources

Cervical lymph node metastases of squamous cell carcinoma from an unknown primary.

Cervical lymph node metastases of squamous cell carcinoma from occult primary constitute about 2-5% of all patients with carcinoma of unknown primary site (CUP). Metastases in the upper and middle neck are generally attributed to head and neck cancers, whereas the lower neck (supraclavicular area) involvement is often associated with primary malignancies below the clavicles. The diagnostic procedures include physical examination with thorough evaluation of the head and neck mucosa using fiber-optic endoscopy, biopsies from all suspicious sites or blindly from the sites of possible origin of the primary, computer tomography and/or magnetic resonance. A systematic tonsillectomy in the absence of suspicious lesions is often recommended since up to 25% of primary tumors can be detected in this site. The thoracic primary (tracheal, bronchial, lung, esophagus) has to be excluded, especially in the case of lower neck involvement. Positron emission tomography (PET) with fluoro-2-deoxy-D-glucose allows detection of primary tumor in about 25% of cases, but this procedure is still considered investigational. Therapeutic approaches include surgery (lymph node excision or neck dissection), with or without postoperative radiotherapy, radiotherapy alone and radiotherapy followed by surgery. In early stages (N1), neck dissection and radiotherapy seem to have similar efficacy, whereas more advanced cases (N2, N3) necessitate combined approaches. The extent of radiotherapy (irradiation of bilateral neck and mucosa versus ipsilateral neck radiotherapy) remains debatable. A potential benefit from extensive radiotherapy should be weighted against its acute and late morbidity and difficulties in re-irradiation in the case of subsequent primary emergence. The role of other methods, such as chemotherapy and hyperthermia, remains to be determined.

Carcinoma, Squamous Cell↗

Radiotherapy-induced thyroid disorders.

Despite their specific functional consequences, radiotherapy-induced thyroid abnormalities remain under-estimated and underreported. These sequelae may include primary or central hypothyroidism, thyroiditis, Graves' disease, euthyroid Graves' ophthalmopathy, benign adenomas, multinodular goitre and radiation-induced thyroid carcinoma. Primary hypothyroidism, the most common radiation-induced thyroid dysfunction, affects 20-30% of patients administered following curative radiotherapy to the neck region, with approximately half of the events occurring within the first 5 years after therapy. The relative risk of radiation-induced cancer (mainly well-differentiated tumours) is 15-53-fold higher than in non-irradiated population. The aetiology of radiation-induced thyroid injury includes vascular damage, parenchymal cell damage and auto-immune reactions. Total radiotherapy dose, irradiated volume of the thyroid gland, and the extent of prior thyroid resection are among the most important factors associated with the risk of hypothyroidism. The contribution of other treatment modalities (chemotherapy, endocrine therapy) as well as patient- and tumour-related factors is less clear. Reduction in radiation dose to the thyroid gland and hypothalamic/pituitary complex should be attempted whenever possible. New radiotherapy techniques, such as stereotactic radiosurgery, three-dimensional conformal irradiation, intensity modulated radiotherapy and proton therapy allow generally better dose distribution with lower dose to the non-target organs. The diagnostic approach to thyroid radiation injury includes baseline thyroid function assays in all patients undergoing thyroid or parasellar irradiation. Recommended follow-up procedures include at least annual evaluation with a history for symptoms of thyroid dysfunction, clinical examination, and measurement of thyroid hormones and thyrotropin. Management of overt hypothyroidism is based on hormone replacement therapy. Thyroid hormone therapy is also recommended in cases of subclinical hypothyroidism. Treatment of other radiation-induced thyroid disorders (thyroiditis, Graves' disease, thyroid cancer) is similar to that employed in spontaneously occurring conditions. Further improvements in radiotherapy techniques and progress in endocrine diagnostics and therapy may allow better prevention and management of radiation-related thyroid injury.

Adenoma↗

Medical aspects of the National Centre For Oncological Hadrontherapy (CNAO-Centro Nazionale Adroterapia Oncologica) in Italy.

More than 20 hadrontherapy centres are active in the world and about 40,000 patients have been treated, almost 4000 with ions. Physical selectivity and high relative biologic efficiency (RBE) represent the rationale for using ions in the treatment of tumours. The clinical results are very promising and justify the construction of new centres. We present the main characteristics of CNAO (Centro Nazionale Adroterapia Oncologica) and its possible integration in a nationwide network. The Italian project started in 1991 thanks to the activity of the TERA Foundation and was financed by the Italian Government in 2002. The CNAO will be built in Pavia to start clinical activity in 2007. The equipment will include a synchrotron and 3 treatment rooms mainly devoted to carbon ions but able to deliver also protons. The Centre should be able to deliver up to 20,000 fractions / year. The realization of CNAO is part of a more ambitious project to set up an integrated national network. The need of hadrontherapy centres is defined by epidemiological studies based on Italian tumour registries showing that almost 900 patients can be electively treated with protontherapy and about 10,000 could be included in clinical trials. Considering that ions could be used for radioresistant tumours that affect about 25,000 new patients/year, we estimate that 10-15%, i.e. 3000-4000 patients would benefit from ion therapy. The realization of a nationwide network possibly linked to a larger European network will be very helpful in making available hadrontherapy for a large part of the population.

Carbon↗

Less aggressive surgery and radiotherapy is the way forward.

PURPOSE OF REVIEW: Conserving the breast is one of the main objectives in treating patients affected by carcinoma. This objective should be compatible with good local control to keep the risk of local failures low. The progressive reduction of the extension of surgery in the breast and in the axilla is now accompanied by a reduction of the radiation field. This article provides an update on conservative therapy for breast cancer. RECENT FINDINGS: After the development of quadrantectomy, the effectiveness of sentinel node biopsy was demonstrated in the axillary staging of breast carcinoma. The situation took another step forward with partial breast irradiation. The highest incidence of local relapse after breast-conserving surgery is observed in the same area as the primary tumor. This factor provides the rationale for reducing the radiation field to a limited area of the breast primarily affected by carcinoma. SUMMARY: The Milan I trial on breast conservative surgery provided definitive confirmation of the equivalence of quadrantectomy, followed by radiotherapy, to mastectomy in terms of local control of disease. The randomized trial on sentinel node biopsy demonstrated the effectiveness of this procedure in axillary staging of breast carcinoma. Radiotherapy is currently under investigation in terms of limiting the radiation field to the affected quadrant of the breast by means of various techniques.

Breast Neoplasms↗

Male breast cancer: a special therapeutic problem. Anything new? (Review).

Carcinoma of the male breast (MBC) is an uncommon phenomenon, accounting for <1% of all malignancies in man. It represents a biologically heterogeneous disorder, and its clinical course may vary from indolent and slowly progressive to rapidly metastatic disease. Most of our current knowledge regarding its biology, natural history, and treatment strategies has been extrapolated from its female counterpart. Information regarding prognostic relevance of new molecular markers is limited. At the European Institute of Oncology we performed a study showing data in which p21Waf1 and p27Kip1 proteins were evaluated in a series of male breast cancer patients. Our data suggest that the immunohistochemical evaluation of p21Waf1 and p27Kip1 expression in male breast carcinomas may be a further useful marker for selecting patients who express functional proteins that can be predictive for the most efficient endocrine response. Moreover, searching for more conservative treatment, we introduced in our clinical practice sentinel node biopsy, and if present, sentinel node biopsy of the internal mammary chain. The potential clinical implications of complete nodal staging are far-reaching, and give us a major new opportunity to stratify male patients with breast cancer for appropriate surgery as well as giving valuable prognostic information. Male breast cancer has biological differences compared with female breast cancer. It responds to hormonal manipulation and chemotherapy, but optimal treatment regimens in males are unknown. By analogy to the female breast cancer, post-mastectomy radiotherapy should be proposed in case of advanced T stage and/or lymph node positivity (considering the small volume of the male mammary gland, we suggest post-mastectomy irradiation in case of T >1 cm and/or presence of >1 metastatic axillary lymph node). Breast conserving surgery, performed in selected cases of male breast cancer, should be always followed by radiotherapy. Despite a wealth of small retrospective studies on MBC, its rarity means there is a lack of prospective randomized controlled treatment trials, which needs to be addressed if significant advances are to be made in the treatment of this unusual challenging disease.

Breast Neoplasms, Male↗

Full-dose intraoperative radiotherapy with electrons during breast-conserving surgery.

HYPOTHESIS: The current standard treatment for early breast cancer includes conservative surgery followed by entire breast radiotherapy (RT). Recent study findings show that most local recurrences are in the scar tissue area suggesting that whole-breast RT may not always be necessary. If the volume of breast tissue to be irradiated is limited, RT may be performed intraoperatively. Intraoperative RT delivered with electrons at the total isodose of 2100 rad (21 Gy) could in principle substitute the currently used radiation course of external RT after breast-conserving surgery in selected cases. PATIENTS AND METHODS: We report our findings on intraoperative RT using a specially designed mobile linear accelerator delivering 4 energy levels of electrons (3, 5, 7, and 9 MeV) via a head maneuvered by a robot arm. We applied this technique to 237 patients with breast cancer (mean age, 59 years; age range, 33-80 years) with tumors smaller than 2 cm in maximum diameter (T1); most underwent wide resection and an axillary sentinel node biopsy. RESULTS: After a median follow-up of 19 months (range, 7-33 months), the rate of posttreatment complications is very low. Four patients (1.7%) developed breast fibrosis-mild in 3 patients and severe in 1 patient-that resolved in 24 months. Three patients (1.4%) developed ipsilateral breast cancer-2 (1.0%) contralateral breast cancer, 1 (0.5%) supraclavicular node metastasis, and 1 (0.5%) distant metastases. CONCLUSIONS: Intraoperative RT with electron beams reduces irradiation to the skin, subcutaneous tissue, and contralateral breast and lung. It appears to be a promising method for irradiating conservatively treated breasts and it avoids the long period of postoperative RT that may not be easily accessible to all patients.

Adenocarcinoma↗

Finding dose-volume constraints to reduce late rectal toxicity following 3D-conformal radiotherapy (3D-CRT) of prostate cancer.

BACKGROUND AND PURPOSE: The rectum is known to display a dose-volume effect following high-dose 3D-conformal radiotherapy (3D-CRT). The aim of the study is to search for significant dose-volume combinations with the specific treatment technique and patient set-up currently used in our institution. PATIENTS AND METHODS: We retrospectively analyzed the dose-volume histograms (DVH) of 135 patients with stage T1b-T3b prostate cancer treated consecutively with 3D-CRT between 1996 and 2000 to a total dose of 76 Gy. The median follow-up was 28 months (range 12-62). All late rectal complications were scored using RTOG criteria. Time to late toxicity was assessed using the Kaplan-Meyer method. The association between variables at baseline and > or=2 rectal toxicity was tested using chi(2) test or Fisher's exact test. A multivariate analysis using logistic regression was performed. RESULTS: Late rectal toxicity grade > or=2 was observed in 24 of the 135 patients (17.8%). A 'grey area' of increased risk has been identified. Average DVHs of the bleeding and non-bleeding patients were generated. The area under the percent volume DVH for the rectum of the bleeding patients was significantly higher than that of patients without late rectal toxicity. On multivariate analysis the correlation between the high risk DVHs and late rectal bleeding was confirmed. CONCLUSIONS: The present analysis confirms the role of the rectal DVH as a tool to discriminate patients undergoing high-dose 3D-CRT into a low and a high risk of developing late rectal bleeding. Based on our own results and taking into account the data published in the literature, we have been able to establish new dose-volume constraints for treatment planning: if possible, the percentage of rectal volume exposed to 40, 50, 60, 72 and 76 Gy should be limited to 60, 50, 25, 15 and 5%, respectively.

Aged↗

In vivo dosimetry using radiochromic films during intraoperative electron beam radiation therapy in early-stage breast cancer.

BACKGROUND AND PURPOSE: To check the dose delivered to patients during intraoperative electron beam radiation therapy (IOERT) for early breast cancer and also to define appropriate action levels. PATIENTS AND METHODS: Between December 2000 and June 2001, 54 patients affected by early-stage breast cancer underwent exclusive IOERT to the tumour bed using a Novac7 mobile linac, after quadrantectomy. Electron beams (5, 7, 9 MeV) at high dose per pulse values (0.02-0.09 Gy/pulse) were used. The prescribed single dose was 21 Gy at the depth of 90% isodose (14-22 mm). In 35 cases, in vivo dosimetry was performed. The entrance dose was derived from the surface dose measured with thin and calibrated MD-55-2 radiochromic films, wrapped in sterile envelopes. Films were analysed 24-72 h after the irradiation using a charge-coupled-device imaging system. Field disturbance caused by the film envelope was negligible. RESULTS: The mean deviation between measured and expected doses was 1.8%, with one SD equal to 4.7%. Deviations larger than 7% were found in 23% of cases, never consecutively, not correlated with beam energy or field size and with no evidence of linac daily output variation or serious malfunctioning or human mistake. The estimated overall uncertainty of dose measurement was about 4%. In vivo dosimetry appeared both reliable and feasible. Two action levels, for unexplained observed deviations larger than 7 and 10%, were preliminary defined. CONCLUSIONS: Satisfactory agreement between measured and expected doses was found. The implementation of in vivo dosimetry in IOERT is suggested, particularly for patients enrolled in a clinical trial.

Breast Neoplasms↗

Analysis of mandibular dose distribution in radiotherapy for oropharyngeal cancer: dosimetric and clinical results in 18 patients.

BACKGROUND AND PURPOSE: The relationship between the radiation dose and the risk of the osteoradionecrosis is well known. However, the dose to the mandible is not routinely assessed in the radiotherapy for head and neck cancer. The aim of our study was to analyze the mandibular dose distribution in the patients administered curative radiotherapy for squamous cell carcinoma of the oropharynx. Moreover, the clinical results have been analyzed. MATERIAL AND METHODS: We examined the clinical records and treatment plans in 18 patients treated with bifractionated radiotherapy for stage II-IV oropharyngeal cancer. In 17 patients, the total radiotherapy dose prescribed in the International Committee of Radiation Units and Measurements (ICRU) reference point was 74.4 Gy administered in 62 fractions (1.2 Gy twice daily with 6h interfraction interval) and one patient received a dose of 75.6 Gy. The whole dose to the mandibular-orophryngeal region was delivered with 6 MV photons. The mandible was contoured manually on computed tomographic scans and the point doses at the both mandibular condyles, ascending ramus, mental symphysis, molar and retromolar regions were assessed. Moreover, the cumulative dose-volume histograms (DHVs) were evaluated. The median follow-up period for alive patients is 30 months (range, 21-44+ months). RESULTS: Tumor remission was observed in 17 patients: in 11 cases, complete remission was achieved and in six cases, only partial remission was possible. One patient was lost to follow-up before the first response evaluation. The median survival for all patients is 22 months (range, 3-44+ months). Ten patients are alive and seven died. In six cases, the cause of death was head and neck tumor and in one died due to pancreatic cancer (second primary). No late bone post-radiation complication was seen. The highest radiotherapy doses were observed in the retromolar regions. The mean percentage doses at the right and left retromolar regions were 101.3+/-3.8% (range, 90.2-109.1%) and 101.7+/-2.5% (range, 95.2-105.8%), respectively. Lower doses were seen in ascending ramus (the mean percentage doses at right and left ascending ramus were 97.3+/-8.5% and 97.8+/-7.6%, respectively), the molar regions (the mean percentage doses at right and left molar regions were 86.0+/-13.5% and 88.1+/-12.9%, respectively), and at the mandibular condyles (the mean percentage doses at the right and left mandibular condyles were 72.6+/-18% and 77.0+/-16.5%, respectively). The volume of the mandible ranged from 60.1 to 110.1cm(3) (a mean of of 82.3 cm(3)). In all patients, the maximum dose absorbed in the mandible was higher than the dose prescribed in the ICRU point and the mean maximum dose absorbed in the mandible was 105.7+/-2.1% (range, 102.4-110.6%). The percentage of mandibular volume receiving a dose higher than prescribed was 28.6+/-14.9% (range 10.2-58.1%). The area underlying the DVH curve, the maximum mandibular doses and the retromolar doses did not appear to statistically depend on use of wedge or mandibular volume. CONCLUSIONS: Radiotherapy for oropharyngeal cancer is associated with high doses to the retromolar mandibular regions (the dose can be higher than prescribed in the ICRU reference point), ascending ramus and molar regions. Lower doses are absorbed at the condyles and mental symphysis. The single dose point (for example, the ICRU reference point) could be not used as a representative for the mandibular dose. In our small series of patients treated with hyperfractionated irradiation, these dose heterogeneities were not correlated to the patient- and treatment-related factors and are not related to the increased risk of late bone complications. The clinical relevance of mandibular dose distribution remains to be established in larger series of patients treated with conventionally and unconventionally fractionated irradiation.

Adult↗

Intravascular ultrasound based dose assessment in endovascular brachytherapy.

BACKGROUND: the role of endovascular brachytherapy in restenosis prevention is well documented. Dose is usually prescribed at a fixed distance from the source axis by angiographic quantification of vessel diameter. Recently, intravascular ultrasound (IVUS) was introduced in dose prescription, allowing a better evaluation of the vessel anatomy. This study retrospectively explores the difference between prescription following angiographic vessel sizing and delivered dose calculated with IVUS. METHODS AND RESULTS: Seventeen lesions were studied with IVUS, identifying on irradiated segment, three sections on which measuring minimal and maximal distance from the centre of IVUS catheter to the adventitia; using dedicated software, corresponding doses were calculated. The dose ranged widely, with maximal and minimal values of 71.6 and 4.9 Gy; furthermore, heterogeneity in dose among different sections was observed. In the central section, the maximal dose was 206% of the one prescribed with the QCA model at 2 mm from the source axis, while the minimal dose was 96%. In proximal and distal sections, respective values were 182, 45, 243, and 122%. CONCLUSIONS: Our analysis confirmed the dose inhomogeneity delivered with an angiographic fixed-dose prescription strategy. A dose variation was found along the irradiated segment due to the differences in vessel thickness. IVUS emerged as an important tool in endovascular brachytherapy, especially for irregular-shaped vessels.

Angioplasty, Balloon, Coronary↗

Radiotherapy-induced ear toxicity.

Despite their particular functional consequences, radiotherapy-induced ear injuries remain under-evaluated and under-reported. These reactions may have acute or late character, may affect all structures of the hearing organ, and result in conductive, sensorineural or mixed hearing loss. Up to 40% of patients have acute middle ear side effects during radical irradiation including acoustic structures and about one-third of patients develop late sensorineural hearing loss (SNHL). Total radiotherapy dose and tumour site seem to be among the most important factors associated with the risk of hearing impairment. Thus, reduction in radiation dose to the auditory structures should be attempted whenever possible. New radiotherapy techniques (3-dimensional conformal irradiation, intensity modulated radiotherapy, proton therapy) allow better dose distribution with lower dose to the non-target organs. Treatment of acute and late external otitis is mainly conservative and includes the anti-inflammatory agents (applied topically and systematically). Post-radiation chronic otitis media and the eustachian tube pathology may be managed with tympanic membrane incision with insertion of a tympanostomy tube (grommet), although the benefit of such approach is controversial and some authors advocate a more conservative approach. In these patients the functional deficit can be alleviated by application of bone conduction hearing aids such as, e.g., the bone anchored hearing aid (BAHA). There is no standard therapy for post-irradiation sudden or progressive SNHL yet corticosteroid therapy, rheologic medications, hyperbaric oxygen or carbogen therapy are usually employed (as for idiopathic SNHL), although controversial data on the efficacy of these treatment modalities have been published. In selected cases with bilateral profound hearing loss or total deafness, cochlear implants may prove effective. Further improvements in radiotherapy techniques and progress in otologic diagnostics and therapy may allow better prevention and management of radiation-related acoustic injury.

Audiometry↗

Intracoronary beta-radiation for the treatment of patients at very high risk for recurrence of in-stent restenosis: a single center experience.

BACKGROUND: Intracoronary brachytherapy has significantly reduced the recurrence of in-stent restenosis. The aim of this study was to evaluate the feasibility, safety and efficacy of intracoronary beta-radiation in patients at very high risk for recurrence of in-stent restenosis. METHODS: We analyzed 42 patients with 50 lesions submitted to catheter-based beta-radiation (Beta-Cath System, Novoste Corporation, Norcross, GA, USA) for in-stent restenosis. Thirty-eight lesions were at the second restenosis, 8 at the third, and 4 at the fourth; a diffuse pattern was present in 78%. RESULTS: Balloon angioplasty was performed for 30 lesions (60%) and the cutting balloon technique for 20 (40%). In 12 lesions further 14 stents had to be deployed (28%). The delivery catheter was successfully positioned in 96% of the procedures. The mean dwell time was 179 +/- 50 s with a radiation dose ranging from 18.4 to 25.3 Gy, depending on the vessel size. A complete angiographic success without coronary dissection and without any additional stenting after radiation delivery was achieved in 86%. At follow-up (7.2 +/- 2.1 months), the overall restenosis rate was 30.4% (14 lesions). A recurrence was detected in 1/11 lesions with initial focal pattern and in 13/39 lesions with initial diffuse pattern. The restenosis rate was higher in patients in whom a geographic miss had occurred (p < 0.05 vs lesions without geographic miss) and in those in whom a new stent had been deployed (p < 0.05 vs lesions treated without a stent). CONCLUSIONS: Brachytherapy reduces the in-stent restenosis rate in patients who are at very high risk of recurrence. The restenosis pattern, geographic miss and new stent deployment seem to be negative prognostic factors for recurrence of restenosis.

Aged↗

Surgical technique of intraoperative radiotherapy in conservative treatment of limited-stage breast cancer.

At the European Institute of Oncology, Milan, Italy, we have focused our interest on the use of intraoperative radiation therapy (IORT) in limited-stage breast cancer that is conservatively treated. A new technique to perform IORT was applied in 185 patients from July 1, 1999, to October 31, 2001. As the surgeon plays a crucial role in this procedure in selecting the patients, performing the breast resection, preparing the gland as a target to receive IORT, delivering the radiation directly to the mammary gland via a dedicated applicator, and, finally, reconstructing the breast, each phase of the surgical technique has been completely standardized and is described herein. The use of IORT in the conservative treatment of breast cancer could allow the course of external fractionated-dose radiation therapy to be completely avoided; IORT dramatically reduces radiation exposure of the skin, lung, and subcutaneous tissues and avoids the irradiation of the contralateral breast, which contributes to a very low incidence of radiation-induced sequelae. In our experience, IORT for limited-stage breast carcinoma is easy to perform and only briefly prolongs the duration of the surgical procedure.

Breast Neoplasms↗

Axillary radiotherapy instead of axillary dissection: a randomized trial. Italian Oncological Senology Group.

BACKGROUND: Surgical dissection of the axilla is a standard part of the treatment of breast cancer but, by itself, does not improve prognosis; furthermore, most patients with small-sized breast cancer and a clinically uninvolved axilla never develop axillary metastases. We evaluated disease-free and overall survival in patients with early breast cancer treated by breast-conservation surgery without dissection of axillary lymph nodes, receiving or not receiving axillary radiotherapy (RT). METHODS: From 1995 to 1998, 435 patients older than 45 years with breast cancer up to 1.2 cm were randomized, 214 to breast conservation without axillary treatment and 221 to breast conservation plus axillary RT. RESULTS: After a follow-up of 28 to 68 months (median, 42 months), two women (1%) in the no axillary treatment group and one (.5%) in the axillary RT group developed axillary metastases. Rates of distant metastases and local treatment failure were also very low, and 5-year overall survival was 99%. CONCLUSIONS: After a mean of 46 months of follow-up, our results indicate that axillary dissection can be safely avoided in patients with very small invasive carcinomas and a clinically negative axilla. Whether axillary RT should be added can be assessed only by longer follow-up.

Axilla↗