Anaplastic thyroid cancer: a case report of a long term survival patient and review of literature data.

Anaplastic thyroid carcinoma (ATC) is a very rare disease accounting for less than 2% of all thyroid malignancies and associated to a dismal prognosis. The median survival is between 3 to 9 months with less than 10% of patients alive at 3 years after the time of diagnosis. This low cure rate is due to the late clinical presentation as a bulky unresectable tumour mass often associated with synchronous lung metastases (20-50%). A multimodality treatment consisting in a radical surgery followed by radiotherapy and chemotherapy is reported to be associated with better clinical outcomes while young age (< 65 years), tumour size (< 6.5 cm) and absence of distant metastases at time of diagnosis are recognized as strong prognostic factors of survival. We report the case of a 65 year-old man who was referred to our hospital for an ATC which extended to the external right tracheal wall and muscolar layer of esophagus. The patient underwent radical thyroidectomy with bilateral neck dissection followed by 3 cycles of adjuvant chemotherapy (Cisplatin /Epirubicin) and subsequent radiochemotherapy with Cisplatin as radiosensitizer. At more than 6 years since diagnosis the patient is still alive without evidence of local recurrence or distant metastases. Therefore, aggressive multimodality treatment after radical surgery might improve clinical outcomes and perhaps should be tested in prospective clinical trials.

Ruthenium-106 eye plaque brachytherapy in the conservative treatment of uveal melanoma: a mono-institutional experience.

BACKGROUND: Traditional treatment for uveal melanoma is the enucleation of the eye with outcomes cosmetically unacceptable and loss of useful vision. Plaque brachytherapy, compared to enucleation, had the advantage to preserve the eye with outcomes cosmetically acceptable and preservation of vision. PATIENTS AND METHODS: From July 1990 to December 2009 one hundred forty-two (142) patients (51 males and 91 females) with small to medium uveal melanoma were treated with 106Ru plaque brachytherapy. The patients underwent a complete staging before brachytherapy with indirect ophthalmoscopy and ultrasounds. Mean tumour thickness was 3.26 mm (1.6-6 mm). The dose scheduled was 80-100 Gy to the apex with a maximum dose of 800 Gy to the sclera. RESULTS: One hundred forty-two have been treated, nine patients had lost the follow-up and drop out; 133 patients were assessed. Mean follow-up was 7.7 years (6 months-18 years). The overall survival at 5, 10 and 15 years was 92%, 85% and 78% respectively. Cancer fee survival was 95%, 90% and 83%, respectively at 5, 10 and 15 year. Radiation-induced toxicity was represented in 47 patients with a 5 year actuarial survival rate free from complications of 54%. CONCLUSIONS: 106Ru plaque brachytherapy is a valid approach for treatment of uveal melanoma. This technique is efficacy and safe, with a low toxicity profile.

Radiotherapy and hepatocellular carcinoma: update and review of the literature.

Historically radiotherapy has always played a limited role for the treatment of HCC due to the low tolerance of the liver and the subsequent risk of radiation induced liver disease (RILD). Technologist advancements in radiation planning and treatment delivery such as Stereotactic Body Radiotherapy (SBRT) combined with Image Guided Radiotherapy (IGRT) has allowed us to further increase tumor dose while maximally sparing the surrounding not involved liver. Furthermore, together with the growing knowledge of radiobiological models in liver disease, several mono-institutional retrospective and prospective series are reporting very encouraging results. Therefore, radiotherapy might play a significant role for the treatment of unresectable HCC, alone or combined with other locoregional treatment such as transarterial chemoembolisation (TACE). The rationale for studying this technique is really strong and it should be tested in well designed prospective randomized clinical trials.

Metabolic responses in non-small cell lung cancer after hypofractionated stereotactic radiotherapy PET and hypofractionated radiotherapy.

BACKGROUND: The aim of our study was to evaluate the pattern of local failure after stereotactic body radiotherapy (SBRT) of non small cell lung cancer (NSCLC) lesions relating to different type of 18F-FDG positron emission tomography (PET) response. METHODS: Thirteen NSCLC patients for a total of 15 lesions (primary early or locally advanced and metastases) underwent PET before and 6 months after SBRT. Maximum standard uptake value (SUVmax) <2.5 was considered as cut off for complete response (CR) while lesion reduction > or =50% with residual value above 2.5 for partial response (PR). RESULTS: With a median follow up of 30 months pre- and post-SBRT mean SUV max values were 8.2 (range 14.2-3.7) and 2.4 (range 12.9-0), respectively. No "in field recurrence" was observed while 3 cases of "out field recurrence" occurred as regional nodes progression at 7.8 and 14 months after treatment. Three years overall survival, local control and distant metastases free survival were respectively 66.7%, 63.3% and 44.4%. Actuarial 75% and 53.3% 3-year local control, 60% and 40% 3-years distant metastases free survival were observed for complete and partial PET response, respectively, after SBRT. Thereafter, 60% and 50% 3-year overall survival were observed for complete and partial response. CONCLUSIONS: Clinical results were significantly better for "responder" than "non responder" and for "complete" than "partial response" group. Moreover, our data seem to confirm that a significant subset of patients maintain a low metabolic activity without developing local relapse on longer follow up.

Chronic anemia due to mitomycin C is drug dose-dependent, normocytic, progressive, related to erythropoietin levels and quantitatively predictable: implications for radiochemotherapy.

Mitomycin C (MC) is used as therapy against solid tumors, also combined with other chemotherapeutic agents or radiotherapy. It may cause acute, subacute, or chronic anemia capable of modifying the results of chemo- and radiotherapy. Erythropoietin may be lowered by cancer itself or because of chemoradiotherapy. There are few studies investigating the relationship between erythropoietin and chronic anemia.We prospectively analyzed the chronic anemia and erythropoietin in 38 patients with solid cancer. Patients were 40 to 82 years of age. MC was randomly given every 3 weeks as a single drug at 10 or 20 mg/m². When myelotoxicity occurred the next therapy cycle was delayed until recovery. RBC indices, hemolysis, erythropoietin, liver and kidney function were studied. MC cycles were 136 (3.6 ± 1.4 per pt), 32 being delayed because of myelotoxicity.Hematocrit, hemoglobin and RBC were inversely related to the cumulative dose (r = 0.70 to 0.86; p 0.03 to 0.01) of MC. Other tests remained stable. Anemia occurred almost twofold earlier in the 20 mg/m² group (p=0.049). basal erythropoietin, already lower than in age and sex watched 81 non cancerous subjects (p<0.001), decreased during MC therapy (p<0.01). For each given MC mg/m² a 0.0372 Hb mg/dl reduction occurred. Chronic anemia due to MC is accompanied by erythropoietin reduction. These results can help in designing chemoradiotherapy.

Safety and efficacy of radiotherapy treatment in elderly patients with localized prostate cancer: a retrospective analysis.

The purpose of this study was to evaluate the feasibility and the activity of radiotherapy treatment in patients aged ≥75 with prostate cancer (PC). From January 2000 to December 2007, 107 consecutive patients aged ≥75 years received radiotherapy with radical intent for PC. Eighty-one patients received radiotherapy in combination with a 6 months androgen suppression therapy. Variables considered were age, stage, co-morbidities according to the adult co-morbidity evaluation index (ACE-27) and performance status (PS). The median age was 79.1 years (range 76-87). The 23.4% of patients showed no co-morbidities, while the 46.7% had mild, 23.4% moderate, and 6.5% severe co-morbidities, respectively. All patients completed the planned radiation treatment. At a median follow-up of 37.8 months, the 5-year overall survival rate was 78%. There was a better survival for patients with no or mild co-morbidities (p<0.0001) and a good PS (p=0.009). The actuarial disease-free survival at 60 months was 75.8%. Difference in acute and late toxicity rate was detected between ACE-27 classes for diarrhea and marginally for urinary toxicity, but no difference was detected for different age. We conclude that compliance with radiotherapy is good and rate of toxicity is acceptable in elderly patients. Increasing severity of co-morbidity may sufficiently shorten remaining life expectancy to cancel gains with radical radiotherapy. Further prospective trials are needed to confirm these results.

Glioblastoma in elderly patients: safety and efficacy of adjuvant radiotherapy with concomitant temozolomide.

The aim of this study was to evaluate the impact of radiotherapy plus concomitant and adjuvant temozolomide (TMZ), in terms of feasibility and activity, in elderly patients with glioblastoma. From January 2002 to December 2007, 42 consecutive patients with glioblastoma (27 men and 15 women) aged 65 years or more (median age 71.3 years), received radiotherapy plus concomitant and adjuvant TMZ. Nineteen patients (45.2%) had a Karnofsky index >or=80. Thirty-six patients (85.8%) underwent complete or subtotal resection, while 6 patients (14.2%) were only biopsied. All patients received adjuvant radiotherapy within 4 weeks from surgery. Twenty-two patients (54.8%) underwent adjuvant TMZ. Early discontinuation of concomitant TMZ program due to toxicity was observed in 8 patients. Considered variables were: age, Karnofsky index, surgery versus no surgery, radiation dose, and chemotherapy. At a median follow-up of 10.2 months, the 6- and 12-month overall survival rates were 81.9% and 27.8%, respectively. There was a significantly better survival for patients with a performance status according to Karnofsky >80 (p<0.0001). Actuarial progression-free survival at 6- and 12-month was 46.4% and 9.8%, respectively. Globally, the treatment was well tolerated with no treatment-related toxicity in 69% of patients. In conclusion, in elderly patients, the adjuvant chemo-radiotherapy was well tolerated with an acceptable rate of toxicity, and patients with a good performance status had a significantly better survival. However, further prospective trials are needed to confirm these results.

Safety and feasibility of radiotherapy treatment in elderly non-small-cell lung cancer (NSCLC) patients.

The purpose of this study was to evaluate the feasibility and activity of radiotherapy (RT) treatment in elderly patients with locally advanced lung cancer. From January 2002 to December 2007, 51 consecutive patients (43 men and 8 women) aged > or = 65 received RT for locally advanced lung cancer, 22 with radical intent and 16 in adjuvant setting. Thirty-six patients received chemotherapy. Variables considered were age, co-morbidities, evaluated according to the adult co-morbidity evaluation index (ACE-27), surgery vs. no surgery, radiation dose and chemotherapy. The median age was 74.7 years (range 65-91). Of the patients, 15.7% had no co-morbidity, 41.2% mild, 25.5% moderate, and 17.6% had severe co-morbidities. Sixteen subjects (31.4%) underwent surgery. All patients completed the planned radiation schedule, while chemotherapy was reduced in 16 patients. At a median follow-up of 22 months, the 2- and 3-year overall survival rates were 46.5% and 35.4%, respectively. Patients with no or mild co-morbidities (p < 0.0001) and a good performance status (p < 0.0001) had a better survival. The actuarial progression-free survival at 2 and 3 years was 41.4% and 38.2%, respectively. Acute lung toxicity rates were different between patients with different ACE-27 indexes, whereas late toxicity was not influenced. In conclusion, in elderly patients, the compliance with RT is good and the rate of toxicity is acceptable. Patients with no or mild co-morbidities have a significantly better survival. The increasing severity of co-morbidities may sufficiently shorten the remaining life expectancy, cancel the gains obtained by RT and increase the acute lung toxicity. Further prospective trials are needed to confirm these results.

Adjuvant radiotherapy on older and oldest elderly rectal cancer patients.

The purpose of this study was to evaluate the impact of radiotherapy in terms of feasibility and activity in the patients aged > or = 75 with advanced rectal cancer. From January 2002 to December 2006, 41 consecutive patients (27 men and 14 women) aged > or = 75 received radiotherapy for local advanced rectal cancer, 9 in a pre-operative and 22 in a post-operative setting. Sixteen patients received concomitant chemotherapy. Variables considered were age, co-morbidities, evaluated according to the adult co-morbidity evaluation index (ACE-27), surgery versus no surgery, and timing of radiotherapy. The median age was 80.5 years (range 75-90). A total of 19.5% of the patients had no co-morbidity, 48.8% mild, 17.1% moderate, and 14.6% had severe co-morbidities. Thirty-nine subjects (95.1%) were submitted to surgery. All patients but one completed the planned radiation schedule. At a median follow-up of 23.1 months, the 2- and 4-year overall survival rates were 71.8% and 61.6%, respectively. There was a better survival for patients with no or mild co-morbidities (p=0.002) and a good performance status (p=0.003). The cancer-free survival at 2 and 4 years was 78.9% and 26.4%, respectively. No difference in acute and late toxicity rates was found between patients with different ACE-27 indexes. We conclude that compliance with radiotherapy is good and rate of toxicity is acceptable in elderly patients. Patients with no or mild co-morbidities have a significantly better survival. Increasing severity of co-morbidity may sufficiently shorten remaining life expectancy to cancel gains with adjuvant radiotherapy. Further prospective trials are needed to confirm these results.

Comparison of the effectiveness and tolerability of intravenous or oral glucocorticoids associated with orbital radiotherapy in the management of severe Graves' ophthalmopathy: results of a prospective, single-blind, randomized study.

Eighty-two consecutive patients with moderate-to-severe and active Graves' ophthalmopathy were randomly treated with orbital radiotherapy combined with either oral (prednisone; starting dose, 100 mg/d; withdrawal after 5 months) or iv (methylprednisolone; 15 mg/kg for four cycles and then 7.5 mg/kg for four cycles; each cycle consisted of two infusions on alternate days at 2-wk intervals) glucocorticoids. The two groups did not differ for age, gender, duration of hyperthyroidism and ophthalmopathy, prevalence of smokers, thyroid volume, and pretreatment ocular conditions. Both groups of patients received radioiodine therapy shortly before treatment for Graves' ophthalmopathy. Follow-up lasted for 12 months. A significant reduction in proptosis (from 23.2 +/- 3.0 to 21.6 +/- 1.2 mm in the iv glucocorticoid group, P < 0.0001; and from 23 +/- 1.8 to 21.7 +/- 1.8 mm in oral glucocorticoid group, P < 0.0001) and in lid width (from 13.3 +/- 2.5 to 11.8 +/- 2.2 mm, and from 13.6 +/- 2.0 to 11.5 +/- 1.9 mm, respectively; P < 0.001 in both cases) occurred, with no difference between the two groups. Diplopia significantly improved in both groups: it disappeared in 13 of 27 (48.1%) iv glucocorticoid patients (P < 0.005) and in 12 of 33 (36.4%) oral glucocorticoid patients (P < 0.03). The degree of amelioration of diplopia did not significantly differ between the two groups (P = 0.82). Optic neuropathy improved in 11 of 14 iv glucocorticoid (P < 0.01) and only in 3 of 9 oral glucocorticoid (P = 0.57) patients, with no significant difference in these outcomes. The Clinical Activity Score decreased from 4.5 +/- 1.2 to 1.7 +/- 1.0 (P < 0.0001) in the iv glucocorticoid group and from 4.2 +/- 1.1 to 2.2 +/- 1.2 (P < 0.0001) in the oral glucocorticoid group; final Clinical Activity Score was significantly lower in iv glucocorticoid than in oral glucocorticoid patients (P < 0.01). By self-assessment evaluation, 35 (85.3%) iv glucocorticoid and 30 (73.2%) oral glucocorticoid patients reported an improvement of ocular conditions (P = 0.27). Overall, both treatments produced favorable effects in most patients, but responders in the iv glucocorticoid group (36 of 41, 87.8%) were more than in the oral glucocorticoid group (26 of 41, 63.4%) (P < 0.02). Moreover, iv glucocorticoid treatment was better tolerated than oral glucocorticoid treatment. Side effects occurred in 23 (56.1%) iv glucocorticoid and 35 (85.4%) oral glucocorticoid patients (P < 0.01); in particular, cushingoid features developed in 5 of the former and 35 of the latter patients. One iv glucocorticoid patient had severe hepatitis of undetermined origin at the end of glucocorticoid treatment, followed by spontaneous recovery. In conclusion, high-dose iv glucocorticoid and oral glucocorticoid (associated with orbital radiotherapy) are effective in the management of severe Graves' ophthalmopathy, but the iv route seems to be more effective and better tolerated than the oral route and associated with a lower rate of side effects.

Oral 5-fluorouracil in squamous cell carcinoma of the skin in the aged.

Multiple or recurrent squamous cell skin carcinoma is a rare tumor in the aged. These patients are currently treated with 5-fluorouracil (5-FU) cream as a local chemotherapy; in cases in which the disease progresses, few treatments are available. Two reports deal with the treatment of progressive squamous cell skin carcinoma with systemic 5-FU, but in only eight patients age less than 70 years. We prospectively investigated oral 5-FU therapy in 14 consecutive patients (average age 76 1/2 years) with histologically proven squamous cell skin carcinoma. The disease was aggressive, multiple, or recurrent and had not been eradicated by surgery, radiation therapy, topical 5-FU cream, and non-5-FU chemotherapy. Oral 5-FU was administered as mannitol-coated 5-FU tablets at the daily dose of 175 mg/m2 for 3 weeks every 5 weeks. Toxicity, effectiveness, quality of life, and compliance to therapy were evaluated. Total cycles amounted to 55 (range: 2-6, mean: 4 for each patient) at an average dose intensity of 740 mg/m2/week for from 12 to 36 weeks. Only gastrointestinal toxicity World Health grade I occurred. Quality of life and compliance to therapy were 90%. Therapy induced measurable improvement in nine patients (64.3%): two partial remissions (14.3%), three minimal remissions (21.4%), and four arrests of disease (28.6%) with a median duration of 30+ months. The study ended because of a lack of patients. We can conclude that, if elderly patients require chemotherapy because of progressive multiple or advanced squamous cell skin carcinoma, appreciable results may be obtained with oral 5-FU as a single agent.

[Usefulness of the modified Dixon technique associated with gadolinium administration in the characterization of adrenal masses]. / Utilità della Tecnica di Dixon modificata associata a somministrazione di gadolinio nella caratterizzazione delle masse surrenaliche.

We investigated the usefulness of modified Dixon technique at 0.5 T after Gadolinium (Gd) administration in the characterization of adrenal masses. One hundred and one patients (45 men, 56 women; mean age: 60.5 +/- 13.5 years) with 125 adrenal masses found at previous US or CT of the abdomen were submitted to MRI. The study protocol included preliminary T1-weighted, PD and T2-weighted SE images. A bolus of 0.1 mmol/kg Gd-DTPA was administered and then T1-weighted SE scans were acquired with modified Dixon technique (TR = 450-600 ms, TE = 30 ms, 192 x 192 matrix, no craniocaudal presaturation). Acquisition time is twice as long with this technique as with conventional SE sequences, but three sets of T1-weighted images are acquired: conventional SE, fat-suppressed and water-suppressed images. The diagnosis was made at surgery (18 lesions) and fine-needle biopsy (34 lesions), or with stable US follow-up findings for at least 1 year (73 masses). Adrenocortical adenomas (no. 88) were homogeneously isointense to liver in pre- and postcontrast images, but 32 of them exhibited a small high intensity spot in enhanced fat-suppressed images. Malignant lesions and pheochromocytomas (no. 19) had inhomogeneous signal intensity, with relatively higher signal on T2-weighted and Gd-enhanced fat-saturated images. Fat-water images were useful to assess fatty and myeloid components within myelolipomas (no. 7). Benign conditions were distinguished from malignant conditions with 90% sensitivity, 93% specificity and 92.5% diagnostic accuracy. To conclude, modified three-point Dixon technique after contrast agent administration appears to be another useful diagnostic application of midfield MRI to characterize adrenal tissues.

Postoperative adjuvant chemoradiotherapy for rectal cancer: analysis of acute and chronic toxicity.

AIMS AND BACKGROUND: The aim of the study was to evaluate acute and chronic toxicity of combined postoperative standard radiation therapy to the pelvis and 5-fluorouracil plus levamisole in resectable rectal cancer. METHODS: Between July 1990 and September 1993, 58 patients with histologically confirmed adenocarcinoma of the rectum entered the prospective study. The schedule consisted of 5-fluorouracil, 450 mg/m2 i.v. for 5 days, and from day 28 5-fluorouracil, 450 mg/m2 i.v. weekly for 24 weeks, plus levamisole given orally at the dose of 150 mg every day for 3 days every 2 weeks for 6 months; radiotherapy (180 cGy/day) 5 days a week for a total dose of 45 Gy was administered from day 28. RESULTS: After the first cycle of chemotherapy (before radiotherapy), overall toxicity was mild. During chemoradiotherapy, dose-limiting toxicity was grade 3 diarrhea and proctitis, for which the combined treatment was interrupted for more than 7 cumulative days in 28 patients. During the 24 weeks of weekly 5-fluorouracil (after radiotherapy), no severe toxicity was reported. Three-year survival and progression-free survival were 65% and 50-55%, respectively. CONCLUSIONS: Although adjuvant chemoradiotherapy is usually feasible, in our study toxicity was severe in a substantial proportion of patients, probably due to the schedule applied. We are evaluating the feasibility and toxicity of a combined treatment which includes 5-fluorouracil in continuous chronomodulated infusion during radiotherapy.

Carbogen and nicotinamide combined with unconventional radiotherapy in glioblastoma multiforme: a new modality treatment.

PURPOSE: A new radiotherapy schedule to treat glioblastoma multiforme after surgery, combining nicotinamide and carbogen. METHODS AND MATERIALS: We analyzed 36 patients with glioblastoma multiforme treated after surgery with radiotherapy, Nicotinamide and Carbogen as follows: 7 patients were treated with accelerated fractionation: two fractions/day, 1.5 cGy/fraction, 6 h interval, 5 days/week, total dose 60 Gy in 4 weeks; 8 patients were treated with the same irradiation scheduling plus Nicotinamide at the dose of 4 g and 2 g in capsules, respectively, 1 h before the first and the second irradiation fraction; 21 patients were treated with accelerated radiotherapy, Nicotinamide, and Carbogen (inhaled 10 min before radiotherapy and during the whole course of irradiation). On the basis of surgical removal our patients were subdivided in three groups: totally resected, with residual tumor <50%, or >50%. Radiotherapy with accelerated fractionation was completed in the scheduled time without side effects on the whole group of patients and Carbogen inhalation did not cause significant change of cardiopulmonar parameters. The toxicity observed was predominant in the gastrointestinal tract and was related to Nicotinamide. RESULTS: The median survival time (M.S.T.) was 10 months, as reported by others authors with conventional treatment, but in patients without surgical residual tumor and submitted to the complete treatment schedule, the survival at 35 months was around 25%. CONCLUSIONS: We conclude that this method is feasible with acceptable toxicity; analyzing the survival curves appears to be a trend towards an improvement in survival in the subgroup of patients with gross total removal treated with the combination of Carbogen, Nicotinamide, and accelerated fractionation.

[Adrenal myelolipomas: their magnetic resonance assessment]. / Mielolipomi del surrene: valutazione con risonanza magnetica.

Adrenal myelolipomas are rare nonfunctioning neoplasias consisting of a variable mixture of mature fat and bone marrow tissue. In the present study MRI appearances of six adrenal myelolipomas are presented. MR exams of six patients in which a conclusive diagnosis of adrenal myelolipomas was reached by means of surgery (1 case), US-guided fine-needle biopsy (3 cases) and typical diagnostic imaging in association with stability on US follow-up for at least two years (2 cases) were retrospectively evaluated. MR sequences protocol included pre- and post-contrast (Gd-DTPA) SE T1-weighted images and SE proton density and T2-weighted images. Five adrenal masses were examined by means of combination of gadolinium administration with a SE T1-weighted modified three-point Dixon technique. Three different MR structural patterns were pointed out: a) homogeneous hyperintense masses on T1-weighted images with intermediate signal on T2-weighted images, suggestive for predominantly fat-containing lesions (2 cases); b) heterogeneous masses with fat intensity areas and hyperintense areas on T2-weighted images and on post-contrast T1-weighted images, suitable for mixed fatty and myeloid elements (2 cases); c) nodules hypointense to the liver on T1-weighted images and hyperintense on T2-weighted images and after gadolinium administration, suggesting tumors primarily composed of myeloid cells (2 cases). A precise determination of fatty and myeloid elements within the lesions was observed by means of "water" and "fat" images provided by modified three-point Dixon technique. In conclusion, MRI allows to determine the various structural components of myelolipomas and therefore appears to be a very reliable technique in the diagnosis and characterization of the different structural patterns of this rare adrenal pathology.