Impact of residual disease after "unplanned excision" of primary localized adult soft tissue sarcoma of the extremities: evaluation of 452 cases at a single Institution.

BACKGROUND: Soft tissue sarcomas are often inappropriately excised; it is, however, still a matter of debate whether the presence of residual disease in the re-excision specimen can affect patients' prognosis. The aim of this study is to investigate the impact of re-excision after unplanned surgery of primary soft tissue sarcomas (STS) of the extremities. PATIENTS AND METHODS: We retrospectively evaluated 452 adults with grade 2-3, localized STS (349 primary and 103 unplanned excisions). RESULTS: In the re-excision group, a full 43% of the patients had residual tumor. The re-excision group achieved a significantly better outcome in terms of sarcoma-specific survival (SS) (p = 0.002), local recurrence (LR) (p = 0.004) and distant metastasis (DM) (p = 0.028). Residual tumor was associated with a higher risk of DM (p = 0.005). CONCLUSION: We confirm that unplanned surgery does not compromise patients' prognosis; scar re-excision guarantees at least the same SS, LR and DM rates compared to STS primarily treated in a referral center. Routine use of radiation therapy after re-excision could improve local control. Distant metastases seem to be negatively affected by the presence of residual tumor, and therefore, the use of CT in deep and large STS is suggested. The main goal is to avoid unplanned surgery by referring suspected lumps (especially deep, large, increasing in size) to a specialist center.

Unresectable hilar cholangiocarcinoma: multimodality approach with percutaneous treatment associated with radiotherapy and chemotherapy.

Klatskin-type cholangiocarcinoma is a rare tumor, bearing a very poor prognosis: at diagnosis, most patients can only undergo palliation. Evaluation of outcome, mean survival and quality of life was performed in patients with unresectable hilar cholangiocarcinoma treated with multimodality approach in comparison with surgical palliation, biliary stenting or brachytherapy alone. Twenty-six patients with hilar cholangiocarcinoma were studied: 16 patients were enrolled in the multimodality protocol (bilateral biliary drainage; Iridium-192 brachytherapy; plastic endoprosthesis or metallic stent positioning and external radiotherapy plus systemic chemotherapy), 5 patients underwent surgical palliation and 5 percutaneous decompression alone. Nine patients completed the protocol and 7 were treated with brachytherapy followed by biliary stenting alone. The multimodality approach obtained mean survival (10 months) similar to that for surgery and higher than that of the brachytherapy and metallic stenting groups (6 and 2.75 months, respectively). The average hospital stay (15 days) was lower than that of the surgical group (20 days). A multimodality approach is a suitable alternative to palliative surgery of unresectable hilar cholangiocarcinoma.

Unresectable hilar cholangiocarcinoma: multimodality treatment with percutaneous and intraluminal plus external radiotherapy.

The efficacy of multimodality treatment for unresectable hilar cholangiocarcinoma was evaluated in terms of outcome, survival and quality of life. Eleven patients were enrolled in the following protocol: percutaneous drainage of both right and left biliary systems; Iridium-192 intraluminal brachytherapy; replacement of the drainages with endoprotheses; external radiotherapy. Six patients completed the protocol and 5 were treated with brachytherapy alone. Mean survival was 10.5 months, similar to surgical results and higher than the control group treated with percutaneous stenting (2.75 months) or biliary drainage alone (1.75 months), with an average hospital stay of 10-15 days and no procedure-related mortality.

MACOP-B regimen followed by involved-field radiation therapy in early-stage aggressive non-Hodgkin's lymphoma patients: 14-year update results.

A single-center, retrospective study was conducted to evaluate therapeutic results of the MACOP-B third-generation chemotherapy regimen followed by involved-field radiation therapy in a stage I-II aggressive non-Hodgkin's lymphoma (NHL) patients. From 1986 to 1995, 118 consecutive patients with the diagnosis of aggressive NHL, stage I-IE or II-IIE, with or without bulky disease were treated with MACOP-B regimen followed, when appropriate, by 30-36 Gy involved-field radiation therapy. The complete response (CR) rate was 95% after the combined modality treatment (97% for stage I-IE and 93% for stage II-IIE). Patients with bulky disease had a CR rate of 92%. Treatment was well tolerated and no deaths occurred from acute toxicity. After a median follow-up of 68 months, 24 (21%) patients relapsed. The 14-year projected relapse-free and overall survival rates were 78% and d 69%, respectively. MACOP-B regimen with/without involved-field radiation therapy provides a safe and effective combined modality treatment for early-stage aggressive NHL, with the possibility to definitively cure two thirds of the patients.

[Unresectable hilar cholangiocarcinoma: combined percutaneous and radiotherapic treatment]. / Colangiocarcinoma dell'ilo inoperabile: protocollo di trattamento combinato percutaneo e radioterapico.

PURPOSE: Evaluate, in patients with inoperable hilar CLCA, the efficacy of multimodality treatment (brachiotherapy, chemotherapy, external radiotherapy and endoprosthesis positioning) in terms of survival, quality of life and cost/benefit compared to palliative surgical treatment. MATERIAL AND METHODS: 20 patients with inoperable hilar CLCA were evaluated. Ten were considered for combined palliative and radiotherapy treatment according to the following protocol: percutaneous colangiography followed by positioning of right and left internal biliar drainage (10-12 F); intraductal brachiotherapy using Ir-192 needles was performed (7 Gy). A second administration was after 7 days. Total dose was 14 Gy; the biliar drainages were then replaced by endoprosthesis (12-14 F) and left in position for 3 months in order to model the post-attinic fibrosis and to prevent stenosis; external radiotherapy was administered starting 15 days after last brachiotherapy treatment (26 administrations (180 cGy) in 5 weeks, total 46 Gy); chemotherapy (5 FU: 350 mg/mq/die) for 5 days during the first and the fifth week of external radiotherapy; biliar endoprosthesis were removed by endoscopic and, or transhepatic mode after 3 months from end of therapy, verifying. Cholangiography assessed the patency of the biliar duct. Metallic stents were placed if results were not satisfactory; follow-up was by: hepatic lab work-up, tumoral markers, US or TC evaluated disease progression. RESULTS: In 5 of the 10 patients considered for the combined treatment, 5 patients completed the protocol and 5 were treated only with brachiotherapy because of deterioration of clinical conditions. All patients had initial complete remission of jaundice although it recurred with disease progression that led to death. No acute post-radiotherapy complication was observed. Digestive hemorrhage (chronic post-radiotherapy complication) was the cause of death in one patient. DISCUSSION AND CONCLUSIONS: Good results were observed in the patients that completed the protocol, mean survival was 7,5 months instead of 1,75 months as in patients that underwent only percutaneous drainage. Better results may be obtained taking in consideration the poor clinical conditions of the patients at the time of diagnosis. The proposed therapeutic protocol requires an average hospitalization of 10-15 days instead of 15-20 days as for palliative biliar-digestive deviation, being less invasive and thus associated to lower morbidity and no mortality.

Efficacy of the VBM regimen in the treatment of elderly patients with Hodgkin's disease.

BACKGROUND AND OBJECTIVES: No specific chemotherapy regimens have yet been recommended for elderly Hodgkin's disease (HD) patients. We investigated the therapeutic efficacy and toxicity of the three-drug-combination VBM (vinblastine, bleomycin, and methotrexate) regimen in a group of 19 elderly HD patients. DESIGN AND METHODS: Vinblastine (6 mg/m(2) i.v.), bleomycin (10 mg/m(2) i.v.) and methotrexate (25 mg/m(2) i.v.) were administered on days 1 and 8. Chemotherapy was repeated every 28 days for a total of 6 cycles. Local radiotherapy was given only to patients who presented bulky disease at the time of diagnosis. Of the 19 patients, 13 patients had stage II, 2 stage III, and 4 stage IV disease; the median age was 68 years (range 60 to 75). RESULTS: Of the 19 patients, 15 (79%) achieved complete response (CR) and 3 (16%) partial response, while the remaining patient showed no benefit from the treatment. With a median follow-up of 48 months, the estimated 5-year relapse-free survival was 79%, and overall survival was 64%. Hematologic grade 3-4 toxicity was seen in only 1 (5%) patient; no severe non-hematologic side effects or deaths were associated with the administration of the VBM regimen. INTERPRETATION AND CONCLUSIONS: These preliminary data indicate that the VBM regimen provides a safe and effective therapeutic option for elderly patients with untreated HD.

Radiation-induced gadd45 expression correlates with clinical response to radiotherapy of cervical carcinoma.

BACKGROUND: Recent work has identified a category of genes devoted to the control of genomic stability and prevention of cellular evolution. They encode components of cell cycle checkpoint, i.e., regulatory pathways committed to ordered cell cycle transition and fidelity of replicated DNA under adverse environmental conditions, such as those following exposure to genotoxic agents. Gadd45 belongs to the class II family of DNA damage-inducible (DDI) gene, and its role in DNA repair has been proved in many experimental models. The aim of our study was to correlate gadd45 radio-induction with the responsiveness to radiotherapy of cervical carcinomas, a type of cancer most commonly treated with radiotherapy alone. METHODS: By means of a competitive polymerase chain reaction strategy, we compared in 14 patients the gene expression levels before and during external beam radiotherapy, when a dose ranging from 18 to 25 Gy was delivered to the target. RESULTS: We found a correlation between the lack of gadd45 induction and a good clinical response to radiotherapy, in terms of both local control and disease-free survival. CONCLUSION: Our results support the measure of the induction of gadd45, and possibly of other genes required for regulated G1-S checkpoint, as a method useful for prognostic evaluation of cervical carcinoma patients.

Potentiation of cADPR-induced Ca(2+)-release by methylxanthine analogues.

Caffeine and other methylxanthines are known to induce Ca(2+)-release from intracellular stores via the ryanodine receptor. In the present work, a range of caffeine analogues, in which methyl groups at the 1 and 7 positions were replaced with alkyl chains containing different functional groups (oxo, hydroxyl, propargyl, ester, and acids), were synthesized. These compounds were then screened for their ability to potentiate Ca(2+)-release induced by cADPR (an endogenous modulator of ryanodine receptors) in sea urchin egg homogenates. Two of the synthesized methylxanthines, 1, 3-dimethyl-7-(7-hydroxyoctyl)xanthine (37) and 3-methyl-7-(7-oxooctyl)-1-propargylxanthine (66), were shown to be more potent than caffeine in potentiating cADPR-induced Ca(2+)-release, while 1,3-dimethyl-7-(5-ethylcarboxypentyl)xanthine (14) was shown to be more efficacious. The development of new methylxanthine analogues may lead to a better understanding of ryanodine receptor function and could possibly provide novel therapeutic agents.

ABVD and radiation therapy as first-line treatment in advanced Hodgkin's disease.

The purpose of this study was to evaluate the efficacy of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and radiotherapy in advanced Hodgkin's disease. In addition, to evaluate whether patients with slow responding tumors could profit from the early change of treatment regimen [MOPP (mechloretamine, vincristine, procarbazine, and prednisone)] followed by radiation therapy or autologous bone marrow transplantation (ABMT). Finally, to evaluate treatment options for patients with both early and late relapses. A total of 78 patients with previously untreated stages IIA bulky, IIB, III (A and B), and IV (A and B) Hodgkin's disease were treated with the ABVD regimen followed by radiotherapy. Patients with stages IIIB and IV (A and B) were re-staged after 4 ABVD courses of the treatment: slow responders (response less than 70%) underwent second-line treatment (MOPP) and eventually ABMT. Relapsed patients with a long initial complete response (> or = 12 months) were treated with second-line conventional treatment and those patients with a short initial complete response (< 12 months) underwent ABMT. The complete response (CR) rate was 91% after ABVD and radiation therapy. An additional 5 stage IIIB and IV patients whose therapy was switched after 4 cycles because of a slow response obtained a CR (3 after 2 MOPP courses plus radiotherapy and 2 after 2 MOPP courses followed by ABMT). Including these additional CRs, the overall CR rate was 97%. No episodes of clinical cardiopulmonary toxicity were observed. With a median follow-up time of 42 months, the 4-year relapse-free survival was 87%. The 4-year overall survival was 96%. Ten cases relapsed: all but one obtained a second CR with different approaches depending on the timing of relapse. The ABVD regimen appears to be effective and well tolerated confirming the validity of this four-drug regimen in the treatment of advanced Hodgkin's disease. In addition, therapeutic choices based on the timing of the relapse and the use of re-staging after 4 cycles in order to identify slow responders can play an important role in increasing the number of cured patients.

[External radiotherapy in early stage squamous cell carcinoma of the supraglottic larynx. Report of 28 cases]. / Il trattamento radiante nel carcinoma iniziale (T1-T2N0) sopraglottico. Revisione di una casistica di 28 casi.

The Authors reviewed a group of 28 pts with early-stage supraglottic carcinoma (T1-T2N0), classified according to UICC (1987), and treated exclusively with radiotherapy (RT) between 1980 and 1991. Until 1990 RT was employed for such tumors when surgery was refused or controindicated, while since 1991 primary irradiation (with surgery in reserve) has been considered the treatment of choice. The total dose ranged from 66 to 70 Gy on the larynx and up to 50 Gy on neck nodes. RT was applied in a daily fraction of 2 Gy five times a week. No significant early complications were observed. Only 1 pt showed residual cronical oedema in the arytenoid region. In none of the pts was tracheostomy necessary. The local control rate obtained after 30 months was 85.7% (24/28). Salvage surgery (horizontal supraglottic laringectomy, HSL) was performed in 3 out of 4 pts with local failure and achieved complete control of the disease. In the last pt the surgery was controindicated because of poor general health conditions. The actuarial survival rate after 5 years is 86.2%. The present series was compared to a group of 152 pts with T1-T2N0 supraglottic cancer treated surgically (HSL) at the same Istitution. In these pts local control and the actuarial survival rates are 85.6% and 89% respectively. According to recent Literature data, the present findings confirm that RT may be administered for the treatment of selected early stage (T1-T2N0) supraglottic squamous cell carcinoma of the larynx with oncologic results equivalent to those obtained with radical surgery. The importance of imaging techniques (TC, MRI) in the correct staging of the tumor is emphasised.

[Radiotherapy of stage T1 carcinoma of the glottis. Analysis of prognostic factors in 154 patients]. / La radioterapia dei carcinomi della glottide nello stadio T1. Analisi dei fattori prognostici in 154 pazienti.

A retrospective study was carried out on a series of 154 patients affected with vocal cord cancer in stage T1 treated with definitive radiotherapy April, 1979, to November, 1991. According to the 1992 TNM classification (UICC), 121 patients were classified as stage T1a and 33 patients as stage T1b. All patients were treated using parallel opposed fields of a 60 cobalt unit. Field size ranged from 16 to 30 square centimeters and the dose from 4400 to 7000 cGy, but only 15 patients received less than 6400 cGy. All patients were treated with once-daily fractionation (200 cGy/day). Follow-up ranges from 25 to 123 months; the median is 63 months. We observed 14 local recurrences (9.0%), all but one within 36 months from the end of treatment. Ten of 14 patients (71.4%) were rescued by surgery (8 patients underwent total laryngectomy and 2 conservative surgery); 13 patients were lost for intercurrent deaths. The incidence of recurrences is 7.4% for T1a patients (9/121) and 15.1% for T1b patients (5/33). The total dose does not seem to be related to relapse rate since recurrences were found in 6.6% of patients after a dose < 6400 cGy and in 9.3% of patients who had received higher doses. In our experience, field size did not affect, treatment results (< 25 cm2: 7.5% recurrences, > 25 cm2: 10.7%). Besides lesion volume, the main prognostic factor was overall treatment time. The incidence of failure was 3 times lower (5.8%) in the patients who completed the treatment within 7 weeks than in the patients whose treatment lasted more than 8 weeks (16.6%).