Characteristics of thyroid cancer following irradiation.

Studies in humans and animals have suggested that the distribution of histologic types of radio-induced thyroid cancers is different from that of naturally occurring tumors. In an attempt to verify that finding, histologic results of 31 patients with thyroid cancer, who had received irradiation to the head, neck or upper chest for other causes, were compared with those of 389 non irradiated patients. The two groups were homogeneous for age and sex. There was a significantly higher prevalence of the papillary type in the irradiated group, with an higher incidence of metastatic lymph nodes. Other histopathologic findings, coexisting with the papillary carcinoma (i.e., ground glass subtype, size less than 1.5 cm, multicentricity) did not differ significantly in the two groups. Some theoretical considerations concerning radio-induced thyroid carcinoma are proposed.

Chemoradiotherapy as preoperative treatment in locally advanced unresectable pancreatic cancer patients: results of a feasibility study.

PURPOSE: The combination of radiotherapy and fluorouracil (5-FU) in patients with locally unresectable pancreatic carcinoma has led to a significant increase in survival in comparison with radiotherapy alone. Doxifluridine (5-DFUR) is an orally active fluoropyrimidine, and its cytotoxic metabolite (5-FU) may concentrate in areas of high tumor vascularization. This trial was carried out with the aims of improving locoregional control and making lesions resectable in patients with unresectable pancreatic cancer. METHODS: 5-DFUR was given at a dose of 500 mg/m2 b.i.d. by way of mouth for 4 days every other week for a total of four courses, with leucovorin 25 mg b.i.d. orally being given 2 hours before each 5-DFUR administration. External beam RT was administered at a dose of 1000 cGy per week for 3 weeks, followed by a 2-week break and then by 1000 cGy per week for a further 2 weeks (a total dose of 5000 cGy). The patients were restaged 4 weeks after the end of treatment and explored for resection in cases of partial response (PR). RESULTS: A total of 32 patients were treated between 1992 and 1997. Ab initio unresectability was shown by laparotomy (16 cases) or computed tomography (16 cases), and was due to vascular invasion in 27 patients, massive regional nodal metastases in nine, and both in four. The median age was 63 years (range 36-71); performance status (PS) (ECOG): 0-1 = 28 and PS 2 = 4. All the patients had measurable disease and were evaluable for response. There were seven PR (22%), 10 SD (31%), and 15 PD (47%). All of the responders underwent surgical exploration, and radical resection was possible in 5. Three of these patients are still disease-free with a follow-up of 18, 27, and 65 months; the other two cases relapsed 11 and 14 months after surgery. The median survival time was 9 months for the entire group, and 1-year survival rate was 31%. The treatment was never stopped because of toxicity. There were no CTC-NCI grade 3 or 4 toxic events; grade 1-2 diarrhea was observed in 10 cases. CONCLUSIONS: This preoperative regimen was feasible and led to a successful surgical resection in 16% of otherwise inoperable cases. The median survival was comparable with the results obtained after 5-FU infusion plus radiotherapy. The resectability rate, and the benefit in terms of survival in the resected patients, make these results worthy of confirmation by larger studies.

Design and characterization of a dynamic multileaf collimator.

The characteristics of a prototype computer-assisted dynamic multileaf collimator (DMLC), specifically designed for small-field conformal radiotherapy, were evaluated at the Istituto Nazionale Tumori of Milan. The collimating device consists of two opposing banks of 16 pairs of 8 cm thick, 3.6 mm wide tungsten leaves and allows shaping of a radiation field up to a size of 10 x 10 cm2 at the isocentre. The screening thickness of each leaf is 6.25 mm at the accelerator gantry isocentre. The leaves have a trapezoidal cross section and move along an arched path, thus providing a 'double focused' collimation system. The DMLC was installed on the head of a Varian Clinac 2100C linear accelerator. Mechanical and dosimetric evaluations were performed to test the stability of the mechanical isocentre and to determine leaf leakage, penumbra width, accuracy of leaf positions and uniformity of leaf speed. Displacement of the mechanical isocentre was less than 1 mm at all gantry angles. Standard radiographic films exposed to 6 MV x-ray radiation were used for dosimetric evaluations. Leakage between leaves was less than 2.5%, and leakage through abutted leaves was less than 5.5%. The penumbra width between 20% and 80% isodose at different positions of leaf banks was 2.7 mm in the direction of the leaf motion and 3.1 mm along the side of the leaf with a standard deviation of 0.2 mm in both directions. Accuracy in the positioning of the leaf was 0.3 mm, whereas the maximum repositioning error was less than 0.2 mm. Finally, during movement of the leaves at the maximum speed of 0.5 mm s(-1), the standard deviation of the leaf positioning error was 0.2 mm, proving an accurate uniformity of leaf speed.

Guidelines on artificial nutrition versus hydration in terminal cancer patients. European Association for Palliative Care.

Whether a terminally ill cancer patient should be actively fed or simply hydrated through subcutaneous or intravenous infusion of isotonic fluids is a matter of ongoing controversy among clinicians involved in the care of these patients. Under the auspices of the European Association for Palliative Care, a committee of experts developed guidelines to help clinicians make a reasonable decision on what type of nutritional support should be provided on a case-by-case basis. It was acknowledged that part of the controversy related to the definition of the terminal cancer patient, since this is a heterogeneous group of patients with different needs, expectations, and potential for a medical intervention. A major difficulty is the prediction of life expectancy and the patient's likely response to vigorous nutritional support. In an attempt to reach a decision on the type of treatment support (artificial nutrition vs. hydration) which would best meet the needs and expectations of the patient, we propose a three-step process: Step 1: define the eight key elements necessary to reach a decision; Step II: make the decision; and Step III: reevaluate the patient and the proposed treatment at specified intervals. Step I involves assessing the patient concerning the following: 1) oncological/clinical condition; 2) symptoms; 3) expected length of survival; 4) hydration and nutritional status; 5) spontaneous or voluntary nutrient intake; 6) psychological profile; 7) gut function and potential route of administration; and 8) need for special services based on type of nutritional support prescribed. Step II involves the overall assessment of pros and cons, based on information determined in Step I, in order to reach an appropriate decision based on a well-defined end point (i.e., improvement of quality of life; maintaining patient survival; attaining rehydration). Step III involves the periodic reevaluation of the decision made in Step II based on the proposed goal and the attained result.

Long-term relapses of breast cancer: a neglected but important issue.

The relatively frequent finding of long-term relapses from breast cancer, eight years or more after the mastectomy, could indicate that breast cancer is a particular neoplasm and even suggests that it could be a systemic disease. The study of receptors in cases of long-term relapses instead indicate that breast cancer, with the exception of the presence of hormonal receptors which influence the clinical behavior, is similar to neoplasms that arise in other parts of the body. It is possible that the presence of receptors indirectly conditions the formation of antimitotic factors more effective than those known today, up to determining in some cases the phenomenon of long-term relapses. Such factors are presumably active also for neoplasms arising in other parts of the body.

Utility fo gallium-67 in determining the radicality of lymph node dissections of the neck for metastatic lymph nodes with extranodal spread in patients affected by carcinoma of the head and neck.

AIMS AND BACKGROUND: Based on the fact that scintigraphy more readily reveals uptake of a radioisotope in a superficial position owing to incomplete surgical radicality, the authors examined by 67Ga scintigraphy a group of patients who had undergone dissection of lymph nodes of the neck from carcinoma with extranodal spread. They then checked the follow-up to ascertain the efficacy of 67Ga scintigraphy in relation to the eventual recurrences in the soft tissues of the neck. METHODS: A group of 136 patients were examined by 67Ga scintigraphy and followed for a minimum of 3 years after complementary radiotherapy. A group of 20 patients with no lymph node metastases was used as control to evaluate eventual false positives or false negatives. RESULTS: Recurrences in the soft tissues of the neck occurred in 35 (42.7%) of the 82 patients positive at 67Ga scintigraphy and in 6 (11.1%) of the 54 patients negative at the examination (P = 0.0001). All the patients in the control group were negative at 67Ga scintigraphy and without recurrences. CONCLUSIONS: 67Ga scintigraphy can give reliable information on the risk of recurrences in the soft tissues of the neck. Since in spite of postoperative radiotherapy the percentage of local recurrences in cases with positive 67Ga scintigraphy was rather high (42.7%), the authors propose a scheme of radiotherapy based on administration of a higher dose per fraction on the scintigraphically positive area.

Follow-up of pathological stage I and IIA supradiaphragmatic Hodgkin's disease primarily treated with radiotherapy.

One hundred and fifty-five consecutive previously untreated adult patients with supradiaphragmatic pathologic stage IA (71) and IIA (84) Hodgkin's disease treated only with radiotherapy (RT) at the Istituto Nazionale Tumori of Milano from 1970 to 1978 were reviewed. Staging procedures included lymphangiography and laparotomy in all cases. Most patients were irradiated with a conventional cobalt machine. Mantle fields were adopted for 36.8% of cases, mainly at stage I, whereas 63.2% received mantle plus paraaortal irradiation. Doses were above 40 Gy for involved sites and 35-40 Gy for prophylactically irradiated nodes. Minimum and median follow-up were 30 months and 6 years, respectively. All patients achieved complete remission at the end of RT. As of June 1981, 89 of 155 patients (57.5%) were alive and free from progression, 60.6% at stage I, and 54.8% at stage II. Relapses occurred in 54 of 155 cases (35%) after a median free interval of 21 months. Marginal recurrences accounted for 5.8%, true recurrences for 9%, nodal extensions for 8.4%, and extranodal extensions for 11.6%. Males older than 40 years and mediastinal involvement were correlated with higher relapse rates. Salvage treatment consisted of RT alone in 8 patients and chemotherapy plus or minus RT in 44, whereas 2 patients died before a new treatment could start. As of June 1981, 38 of 54 relapsed patients (70.4%) were alive and disease free, whereas 2 were alive with evidence of disease. Actuarial overall survival at 6 years was 90.3% for all cases, 97.1% for stage I, and 84.8% for stage II. Treatment toxicity was analyzed, and problems concerning surgical staging procedures, optimal RT and role of chemotherapy as primary or salvage treatment were discussed.

Malignant lymphomas of Waldeyer's ring: natural history and survival after radiotherapy.

The natural history of 292 consecutive cases of reticulum cell sarcoma and lymphosarcoma of Waldeyer's ring and the survival rate after radiotherapy are reported. In our institute since 1928 from 30 to 35% of pharyngeal neoplasms have been lymphomas, and of these 55% have been reticulum cell sarcomas, 21% lymphosarcomas, and 1% Hodgkin's disease. This high incidence may probably be ascribed to the fact that in all malignant lymphomas, irrespective of the clinical presentation, a systematic biopsy of the whole Waldeyer's ring was carried out. Pharyngeal lymphomas were confined to Waldeyer's ring in 19.6% of cases, with initial spread to contiguous cervical nodes in 43.8%, to distant nodes in 24.2%, and to extranodal tissues in 12.4%. Lymphography showed abnormal retroperitoneal lymph nodes in 38.3% of cases. There was gastrointestinal involvement either initially or later in 17.6% of cases. High-energy radiation therapy to both sides of the neck was the treatment of choice for local and regional disease. It achieved a five-year survival rate of 41.9% in the group of 97 patients treated during the past decade. The incidence of relapse (recurrence and new manifestations) was highest in the first year after treatment.