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Biomedical subjects

G Sanguineti

Publications and source records attributed to G Sanguineti.

At least 37 records · Page 2Linked to original sources

Chemoradiotherapy as an alternative to radiotherapy alone in fast proliferating head and neck squamous cell carcinomas.

The aim of this pilot study was to explore the prognostic relevance of cell kinetics parameters on the local control of patients affected by head and neck squamous cell carcinoma (HN-SCC), randomly assigned to receive either alternating chemoradiotherapy or partly accelerated radiotherapy. Between 1992 and 1995, 40 patients with HN-SCC at stages III and IV entered the study. Multiple primary tumor biopsies were obtained 6 h after in vivo infusion of bromodeoxyuridine, an analogue of thymidine that is incorporated in DNA-synthesizing cells. In vivo S-phase fraction labeling index (LI), duration of S-phase (TS), and potential doubling time (Tpot) were obtained by analysis of the flow cytometric content of bromodeoxyuridine and DNA. Twenty patients were treated by alternating chemotherapy and conventional radiotherapy (arm A), whereas 20 other matching patients received partly accelerated radiotherapy alone (arm B). Univariate local control analysis showed that LI, TS, and Tpot were not prognostically significant in either arm. However, local control probability at 2 years for fast growing tumors, characterized by a LI of 9%, was higher for patients treated with alternating chemoradiotherapy than it was for those treated with partly accelerated radiotherapy alone (68 versus 39%). Conversely, local control probabilities for slow proliferating tumors (LI, <9%) treated in the two arms were similar. These results suggest a potential role for alternating chemotherapy and radiotherapy in HN-SCC patients with fast growing tumors.

Antineoplastic Combined Chemotherapy Protocols↗

Postoperative radiotherapy for head and neck squamous cell carcinomas: feasibility of a biphasic accelerated treatment schedule.

PURPOSE: It has been suggested that postoperative tumor cell proliferation may influence the outcome of advanced head and neck squamous cell carcinomas treated by surgery and postoperative radiotherapy. This Phase I pilot study was undertaken to determine the feasibility of a biphasic accelerated radiotherapy regimen with early and late concomitant boost delivery for postoperative treatment of patients with advanced head and neck cancers. METHODS AND MATERIALS: From April 1993 to April 1994, 29 patients with advanced head and neck cancers were enrolled in this study after they underwent complete surgical resection. The basic radiation course delivered a median dose of 49 Gy in 25 fractions over 5 weeks at 1.8-2 Gy/fraction. The concomitant boost was delivered to the high-risk areas as a second daily fraction during the first (1.4 Gy/fraction) and fifth weeks (1.6 Gy/fraction). The total dose to the high-risk areas was 64 Gy in 35 fractions over 5 weeks. RESULTS: Twenty-seven patients (93%) completed the treatment without interruptions. Only two patients experienced severe acute toxicity requiring treatment breaks of 6 and 8 days, respectively. All patients developed confluent mucositis; in 69% of the cases it covered >50% of the treated surface. No patient developed Grade 5 (ulceration/bleeding) mucosal reaction. Mucositis required a median time of 7 weeks for complete healing (range 3-43). Two patients developed transient bone exposure. The median weight loss was 5.5% of pretreatment body weight (range 1.2-17.1%), and four patients required nutritional assistance with nasogastric feeding tube. CONCLUSION: The results of this study show that this biphasic acceleration regimen is feasible with acceptable acute toxicity.

Adult↗

Cell kinetics and tumor regression during radiotherapy in head and neck squamous-cell carcinomas.

Head and neck squamous-cell carcinoma (HN-SCC) patient management is mainly based on TNM classification and needs be improved by considering other potentially useful prognostic factors. We examined the pre-radiotherapy tumor potential doubling time (Tpot) evaluated after in vivo infusion of bromodeoxyuridine and flow-cytometric analysis and the early clinical tumor regression after 40 Gy (40 Gy-TR). Tpot values and clinical 40 Gy-TR classes (minor and major) were available for 82 HN-SCC patients. Radiation therapy completion was done either with 1 dose per day (conventional regimen) or 2 doses per day (accelerated regimen). Local control was also available for follow-up times above 4 years. We found that major 40 Gy-TR was strongly correlated with fast tumor growth, characterized by Tpot values below 5 days, and that patients with major 40 Gy-TR showed better local control than those with minor 40 Gy-TR, independently from the radiotherapy regimen type. We also found that treatment completion with accelerated radiotherapy gave better local control for patients with major 40 Gy-TR and fast tumor growth than conventional radiotherapy. Multivariate analysis, performed on all patients, assigned an independent prognostic value to Tpot, tumor classification and 40 Gy-TR.

Adult↗

Dorfman-Chanarin syndrome: a case with prevalent hepatic involvement.

BACKGROUND/AIMS: Dorfman-Chanarin syndrome is a very rare condition determined by an autosomal recessive inherited disorder of neutral lipid metabolism. The syndrome is defined by the association of ichthyosiform nonbullous erythroderma, vacuoles in the leukocytes and variable involvement of liver, muscle and central nervous system. Only 19 cases have been described worldwide. METHODS: We studied a 16-year-old patient with congenital ichthyosis, liver and spleen enlargement and abnormal gamma-glutamyltransferase. Liver biopsy, skin biopsy and blood smear showed abnormal intracellular neutral lipid storage. RESULTS/CONCLUSION: On the basis of clinical and histological findings, the patient was diagnosed as having Dorfman-Chanarin syndrome. This is the fourth reported Italian case, with a prominent skin and hepatic involvement. Liver biopsy, performed in the first instance, was of great importance in reaching a diagnosis.

Adolescent↗

[Toxic shock syndrome due to Streptococcus pyogenes: a case report].

An increasing number of severe invasive Group A streptococcal infections have recently been reported. A new syndrome similar to the staphylococcal toxic shock syndrome, defined "streptococcal toxic shock-like syndrome" is also described. We report a case of streptococcal toxic shock-like syndrome with atypical clinical onset. A 67 years old man was admitted on the emergency department because of pain in the scapular area without fever. The patient developed irreversible shock and died after 36 hours. Diagnosis was made with autopsy. We stress the possibility of infectious cause in presence of severe multi organ failure with rapid clinical exacerbation.

English Abstract↗

In vivo cell kinetics in head and neck squamous cell carcinomas predicts local control and helps guide radiotherapy regimen.

PURPOSE: To determine whether pretherapy cell kinetics can predict local control for patients affected by head and neck squamous cell carcinomas (HN-SCCs) to be treated by primary radiotherapy and, moreover, guide to a choice between conventional and accelerated radiotherapy. PATIENTS AND METHODS: Between 1989 and 1993, 83 patients with stage II to IV HN-SCC entered the study. Multiple primary tumor biopsies were obtained 6 hours after in vivo infusion of bromodeoxyuridine (BrdUrd). In vivo S-phase fraction labeling index (LI), duration of S phase (Ts), and potential doubling time (Tpot) were obtained by analysis of multivariate flow-cytometric data. Between April 1989 and January 1991, 49 patients were treated by conventional radiotherapy (70 Gy in 35 fractions over 7 weeks), whereas, afterwards, 34 patients entered an accelerated radiotherapy regimen with the concomitant boost technique (75 Gy in 40 fractions over 6 weeks). RESULTS: Univariate analysis showed that, among patients treated by conventional radiotherapy, local control probability was affected by tumor stage (P = .02), Tpot (P < .001), and LI (P = .04). Similarly, among patients treated with accelerated radiotherapy, we found that local control probability was related to tumor stage (P = .03) and primary tumor site (P = .05). For the subgroup of patients with tumors characterized by fast growth (Tpot < or = 5 days), accelerated radiotherapy gave a better local control rate than conventional radiotherapy (P = .02). Cox multivariate analysis of the total number of patients showed that the only significant independent prognostic factors related to local control were tumor stage (P = .002) and Tpot (P = .004). Moreover, when the Cox analysis was restricted to the subgroup of patients treated with conventional radiotherapy, Tpot was the most significant factor to predict local outcome (P < .01). CONCLUSION: Pretreatment tumor Tpot appears to be an important independent prognostic factor for local control of HN-SCC treated by primary radiotherapy.

Aged↗

Primary site as predictive factor of local control in advanced head and neck tumors treated by concomitant boost accelerated radiotherapy.

AIMS AND BACKGROUND: The purpose of this phase II study was to assess the efficacy and toxicity of an accelerated radiotherapy schedule with the concomitant boost technique in the management of patients with advanced head and neck squamous cell carcinomas (HN-SCC) of various primary sites. METHODS: From May 1989 to December 1992 45 patients were scheduled to receive a total dose of 75 Gy in 40 fractions over 40 days. The boost encompassing the macroscopic disease was given as a second daily dose during the last 2 weeks of the basic treatment. RESULTS: Severe mucositis was recorded in 27 (60%) patients. Late side effect occurred in 2. As regards local control the primary tumor site was the most significant prognostic factor: at a median follow-up of 24 months (range 12-52 months) the actuarial local control rate was 79%, 48% and 15% for oronasopharyngeal, laryngohypopharyngeal and oral cavity primary sites, respectively (p = 0.004). CONCLUSIONS: This high dose concomitant boost regimen appears feasible in advanced HN-SCC. However, our results indicate the primary tumor site as a major prognostic factor even with an accelerated treatment schedule.

Adult↗

[Accelerated radiotherapy with the concomitant-boost technic in patients with squamous cell carcinoma of the head and neck].

The purpose of this phase I-II study was to assess the efficacy and toxicity of an accelerated radiation therapy schedule in patients affected with head and neck squamous cell carcinomas of various primary sites. We adopted the concomitant boost technique which allows 1-2 weeks' shorter treatment time by delivering the boost treatment phase as second daily dose during the last part of the basic field irradiation. May 1989 to December 1992, fifty-one patients were scheduled to receive a total dose of 71-75 Gy in 40 fractions over 6 weeks. The boost encompassing the macroscopic disease was given as second daily dose during the last two weeks of the basic treatment. Severe mucositis was observed in 62% of the patients. Late side-effects occurred in 4 patients. At a median follow-up of two years (range: 12-56 months), actuarial locoregional control rate is 44% and overall survival is 54%. At univariate analysis, primary site is the only predictive factor of locoregional control (p = 0.009): neoplasms arising from the oral cavity did worse than those from larynx/hypopharynx and oro/nasopharynx. We conclude that this regimen is feasible in head and neck squamous cell carcinoma of various primary sites. However, since primary site seems to exhibit a predictive value, data from controlled studies are needed to assess its role in primary sites other than oropharynx and nasopharynx.

Carcinoma, Squamous Cell↗

Potential doubling time in head and neck tumors treated by primary radiotherapy: preliminary evidence for a prognostic significance in local control.

PURPOSE: The aim of the study was to determine preliminarily whether cell kinetic parameters evaluated using in vivo infusion of bromodeoxyuridine (BrdUrd) and flow cytometry, play a role as prognostic factors of loco-regional control in squamous cell head and neck carcinoma treated with radiotherapy. METHODS AND MATERIALS: Between April 1989 and December 1991, 42 patients with unresectable Stage II-IV squamous cell carcinoma of the oral cavity, pharynx or larynx were given an infusion of BrdUrd solution prior to primary tumor biopsy sampling at 4-6 hr later. The simultaneous labeling S-phase fraction (LI) and duration (Ts) as well as the estimated potential doubling time (Tpot) were measured using flow cytometric analysis of BrdUrd and DNA content. Twenty-six patients received standard radiotherapy (70 Gy/35 fractions/7 weeks) whereas 15 patients were treated with the concomitant boost technique (75 Gy/40 fractions/6 weeks). RESULTS: A complete set of flow cytometric data was available for 31 patients. The median value of LI, Ts, and Tpot were 9%, 9 hr and 5 days, respectively. Univariate analysis among the patients treated homogeneously by standard radiotherapy, indicated that local control was affected by Tpot value (p = 0.02). When the same analysis was performed for the patients treated with either standard radiotherapy or concomitant boost regimen, we found a p = 0.04. Thus, patients with a tumor Tpot value < or = 5 days had a significantly lower three-year local control than patients with Tpot > 5 days. Log-rank test univariate analysis showed, in addition, that nodal status was the strongest prognostic factor of local control (p = 0.005). Age, tumor stage, tumor site, performance status, grading, radiotherapy regimen, DNA ploidy and LI value were, instead, not significantly related to loco-regional control. Finally, when comparing the type of radiotherapy for tumors with Tpot < or = 5 days, we found a trend toward a better local control after concomitant boost regimen, with respect to standard regimen (p = 0.06). CONCLUSION: The present preliminary results suggest that Tpot could play a role as additional prognostic factor influencing the disease outcome in head and neck carcinoma treated by radiotherapy.

Actuarial Analysis↗

Treatment of advanced squamous-cell carcinoma of the head and neck with alternating chemotherapy and radiotherapy.

BACKGROUND: For patients with advanced, unresectable squamous-cell carcinoma of the head and neck, radiotherapy is the standard treatment but has poor results. We therefore designed a randomized trial to determine whether alternating chemotherapy with radiotherapy would improve the survival of such patients. METHODS: Patients in the trial had biopsy-confirmed unresectable, previously untreated Stage III or IV, squamous-cell carcinoma of the oral cavity, pharynx, or larynx. They were randomly assigned to chemotherapy consisting of four cycles of intravenous cisplatin (20 mg per square meter of body-surface area per day for five consecutive days) and fluorouracil (200 mg per square meter per day for five consecutive days) alternating with radiotherapy in three two-week courses (20 Gy per course; 2 Gy per day, five days per week), or to radiotherapy alone (up to 70 Gy; 2 Gy per day, five days per week). RESULTS: The 80 patients given chemotherapy alternating with radiotherapy and the 77 given radiotherapy alone were comparable in terms of age, sex, performance status, disease stage, and site of the primary tumor. Complete responses were obtained in 42 percent of the patients in the combined-therapy group and 22 percent of those in the radiotherapy group (P = 0.037). The median survival was 16.5 months in the combined-therapy group and 11.7 months in the radiotherapy group (P less than 0.05); the 3-year survival was 41 percent and 23 percent, respectively. Severe mucositis occurred in 19 percent of the patients in the combined-therapy group and 18 percent of those in the radiotherapy group. CONCLUSIONS: In patients with advanced unresectable squamous-cell carcinoma of the head and neck, chemotherapy alternating with radiotherapy increases the median survival and doubles the probability of survival for three years as compared with radiotherapy alone. However, since local disease cannot be controlled in over half the patients who receive the combined treatment and since almost two thirds die within three years, further improvements in management are necessary.

Antineoplastic Combined Chemotherapy Protocols↗

[The predictability of the radiotherapy response in epidermoid tumors of the head and neck. A review of the literature and mathematical models for choosing the fractionated doses].

Literature data show that the term "squamous-cell head and neck cancer" includes a wide range of epidermoid cell subgroups, each of them with its own intrinsic radiosensitivity (Do values ranging from 107 to 184 in primary tumors, and 146-263 in recurrences; n values ranging from 1 to 5; and, if we consider linear-quadratic model alpha values from 0.273 to 0.490 and beta values from 0.029-0.045). Different sublethal and potential lethal repair times are also observed (4-6 hours and 12-24 hours, respectively), and structural tissue heterogeneity (hypoxic fraction oscillating 5%-30% of the neoplasm). Most important, different kinetic parameters are demonstrated, with Labelling Index ranging from 4% to 30%, phase-S time from 6 to 19 hours, and potential doubling time from 2 to 20 days. On the basis of Fowler's and Barendsen's mathematical models and knowing the potential doubling time and Labelling Index values (derived from bioptic specimens), as well as alpha/beta ratio for both tumor and normal tissue, we tried to identify the optimal fractionation (standard, accelerated, hyperfractionated) for slow/fast-growth tumors, also evaluating the relative acute and late side effects. Our analysis shows that: 1) tumors with aggressive biological behavior (Labelling Index greater than 15%, aneuploidy, potential doubling time less than 5 days) seem to respond to accelerated fractionation/hyperfractionation without split better than to standard regimens: 2) tumors with slow growth (Labelling Index less than 15%, potential doubling time greater than 5 days, euploidy) seem to respond not only to standard regimens, but also--and mainly--to hyperfractionation.

Carcinoma, Squamous Cell↗

[A proposal for the treatment technique for the breast and regional lymph nodes in patients with conservatively operated neoplasms].

Adequate irradiation of regional lymph-nodes in selected patients seems to improve disease-free and over-all survival rates. Technically, regional lymph-nodes are generally treated separately (supra-infra clavicular, apex of axilla and internal mammary chain-IMC). About the treatment of the IMC nodes, there are two main problems: the identification of the individual target volume, and its correct irradiation. For the latter problem, the most employed solutions are: the inclusion of IMC in the tangential fields, the use of the direct or oblique electron beam for IMC alone. None of them is optimal regarding to the tolerance of adjacent critical organs and from a geometric and dosimetric point of view. In this paper we propose and discuss a modified method. The IMC nodes together with the breast are irradiated by a three field technique (two tangential photon beams and one oblique electron beam). Their arrangement allows to treat every part of the target by two fields, reducing the risk of hot and cold spots. This is obtained by extending the internal tangential photon beams to cover the electron beam. Wedges and different weights must be used to achieve an uniform dose distribution.

Breast Neoplasms↗

[The role of radiotherapy in the multimodal treatment of locally advanced breast carcinoma].

From September 1983 to March 1988, 57 patients with locally-advanced breast cancer were treated at the Istituto Nazionale per la Ricerca sul Cancro in Genoa, Italy. All patients received 3 cycles of induction chemotherapy with estrogenic recruitment before surgery (diethylstilbesterol-DES-FAC) and 6 additional cycles of chemotherapy (3 DES FAC alternating with 3 DES CMF) after surgery. Stage III A (15) patients reached 86% local relapse-free survival (LRFS), 68% disease-free survival (DFS), and 85% overall survival (OS). Stage III B (42) patients had 82% LRFS, 59% DFS, and 33% OS at 5 years. The first site of relapse was locoregional in 35% of the patients: 19% chest wall recurrence, 3.5% chest wall and lymph nodes, and 7% regional nodes; 5% of the cases presented synchronous local and systemic recurrence; distant metastases represented 21% of the initial relapse rate. This therapy appears to improve the prognosis of III A patients more than that of III B patients. Unsatisfactory results were obtained in inflammatory cancer, with 54% of local recurrences. The present study indicates that radiotherapy is necessary to improve local control and to increase DFS in inflammatory breast cancer. Moreover, the use of radiation therapy also improves the results in III A and III B patients.

Adult↗

[Cutaneous tuberculosis with multifocal visceral involvement].

The case of a young Senegalese man who developed a form of cutaneous tuberculosis associated with a disseminated disease, successfully treated with appropriate antitubercular chemotherapy is reported. We found Mycobacterium Microti in the cutaneous ulcers, the only organism isolated after many cultural and microscopical examinations of different exudates and tissues. This mycobacterium was considered up to now to be pathogenic to rodents, but not man. Its possible pathogenicity to man (under certain situations) is also suggested, and it is expected that this possibility will be supported by other reports in the near future. In addition, stress is laid on the problems of diagnosis and classification of the cutaneous tuberculosis, so uncommon in the Western Hemisphere, and its possible association with leprosy.

Antitubercular Agents↗

Laryngeal long-term morbidity after supraglottic laryngectomy and postoperative radiation therapy.

PURPOSE: This study was performed to investigate factors associated with laryngeal morbidity when postoperative radiation therapy (RT) is added to supraglottic laryngectomy. MATERIALS AND METHODS: From 1980 to 1994, 56 patients affected with T1 to 4 N0 to 2c supraglottic squamous cell carcinoma selected for standard (59%) or extended (41%) supraglottic laryngectomy at 2 different institutions were retrospectively analyzed. Most of the patients (91%) also underwent neck dissection. Approximately 80% of the patients had stage T4 primary lesions or N2 neck disease. Postoperative RT was added for presumed microscopic disease at the primary site (13 patients), regional nodes (23 patients), or both (20 patients). Median delivered doses to the larynx and to the neck were 50 Gy (range, 40 to 64 Gy) and 46 Gy (range, 40 to 64 Gy), respectively. Median follow-up for living patients is 11 years (range, 2.8 to 16.9 years). Laryngeal complication was defined as the appearance of grade 2 or higher toxicity according to the European Organization for Research and Treatment of Cancer (EORTC) and the Radiation Therapy Oncology Group (RTOG) scoring systems. RESULTS: Two- and 5-year actuarial locoregional control rates were 85+/-5% and 83+/-5%, respectively. Thirty patients (54%) developed laryngeal complications. However, just one patient experienced grade 4 laryngeal oedema requiring permanent tracheostomy. Estimated actuarial survival without laryngeal complications were 50+/-7%, 43+/-7%, and 39+/-7% at 2, 5, and 10 years, respectively. At univariate analysis, treated volumes (P = .03) and total dose to the larynx (P = .03) were significantly associated with local toxicity. A trend was observed also for the maximum dose to the neck (P = .06) and dose per fraction (P = .09). A multivariate Cox proportional hazards model showed total dose to the larynx to be the only independent predictor of toxicity (P = .03). The hazard ratio of laryngeal toxicity was 2.2 (95% confidence interval: 1.1/4.6), for a total dose to the larynx greater than 50 Gy. CONCLUSION: After supraglottic laryngectomy, postoperative RT to the neck does not affect local morbidity, but careful RT treatment planning is necessary to avoid delivering a total dose to the larynx greater than 50 Gy.

Actuarial Analysis↗