Radiotherapy in the treatment of breast carcinoma

In the treatment of breast cancer a radiation therapy is indicated under the following conditions: 1. Postoperative irradiation only of the regional lymph-nodes also in stage I (T1, N0). 2. Postoperative irradiation of the regional lymph-nodes and the thorax wall in cases with great primary tumours (T2), in cases with involved axillary lymph-nodes and, of course, in all cases with "grave signs". 3. Preoperative irradiation only in those cases when it seems possible that an inoperable tumour would become operable. 4. As the sole local treatment only in cases with very large inoperable tumours or in special cases (e.g. very high risc or refusal of the operation). 5. As local treatment of a local recidive or of isolated metastases. 6. As supporting local therapy (e.g. threatening fracturation of our fracturated bone metastases; brain metastases) in cases of generalized metastatic disease treated by hormonal or cytostatic therapy.     

Radiotherapy in the treatment of solitary plasmacytoma

Solitary plasmacytoma of bone (SPB) and extramedullary plasmacytoma (EMP) are rare. High local control rates are reported with radiotherapy, although the optimal dose and extent of radiotherapy portals remains controversial. Between 1983 and 1993, 30 patients with solitary plasmacytoma were seen at the Regional Cancer Centre, Trivandrum, India. 23 patients had SPB and seven EMP. The mean age was 52 years and the male to female ratio 3.2:1. Diagnosis of SPB was confirmed by biopsy in 16 patients and tumour excision in seven. 20 patients received megavoltage radiotherapy to the bone lesion with limited margins, and one received chemotherapy. Two patients who underwent complete tumour excision received no further treatment. All seven patients with EMP received megavoltage radiotherapy, four following biopsy and three after tumour excision. Local control was achieved in all patients with SPB. Nine progressed to multiple myeloma and one developed a solitary plasmacytoma in another bone. Six patients with EMP achieved local control. Three later progressed to multiple myeloma and one had local relapse. Median time to relapse was 28 months in SPB and 30 months in EMP. 5-year overall survival rates were 82% and 57% for patients with SPB and EMP, respectively. The corresponding progression free survival rates were 55% and 50%, respectively. Age, sex, site of tumour, serum M protein and haemoglobin levels did not significantly influence progression free survival. The extent of surgery, radiotherapy dose or time to relapse were not significant prognostic factors. Radiotherapy appears to be an effective modality of treatment of solitary plasmacytoma. No dose-response relationship is observed, and high local control rates are achieved with limited portals. Progression to multiple myeloma is the commonest pattern of failure, although no prognostic factors for progression are identified. The role of chemotherapy in preventing disease progression needs further evaluation.     

Monoclonal antibodies in the treatment of human B-cell malignancies

Monoclonal antibody technology emerged in the 1970's and was greeted by a wave of optimism. Many believed this new form of therapy would be effective in the treatment of human cancers. Early clinical trials in B-cell lymphomas demonstrated both the potential and limitations of unlabeled murine monoclonal antibody therapy, and taught us valuable lessons regarding the importance of the antibody structure, and nature of the targeted antigen. Since that time modifications in antibody structure and careful selection of target antigen have improved the clinical efficacy of these agents. Clinical trials using humanized antibodies have demonstrated that human/mouse chimeric antibodies and humanized antibodies have enhanced anti-tumor activity, decreased immunogenicity, and a very favorable toxicity profile. Radiolabeled monoclonal antibodies can induce durable remissions in lymphoma with toxicity limited largely to bone marrow suppression. Clinical trials with immunotoxins have demonstrated anti-tumor activity but also have been associated with significant toxicity. Standard treatment options for B-cell lymphoma will soon include antibody-based therapies. Further basic and clinical research is needed so we can understand more thoroughly the mechanisms responsible for the observed anti-tumor effects, and explore more extensively the best approach to their clinical use.     

Antimicrobial treatment of dermatologic preparations with peracetic acid. 1]

The therapeutic effect of orally administered zinc in 3 patients affected with Acrodermatitis enteropathica is reported. Single daily doses of zinc resulted in rapid improvement of the general condition of these patients and in clinical remission within a week. Serum, urine and hair zinc levels as well as alkaline phosphatase, which were very low before treatment, returned to normal after therapy. This brief report confirms the efficacy of oral zinc in the treatment of Acrodermatitis enteropathica.     

Lasers in dermatologic surgery

The authors review their experiences with the use of carbon-dioxide (CO2) lasers in dermatological surgery in a group of 3000 patients, with a total number of 3920 tumorous skin lesions, during a three-year period. The word LASER is an acronym for L-ight A-mplification by S-timulated E-mission of R-adiation. It must be pointed out that it is electromagnetic radiation, not X-irradiation. In regard to the spectrum laser light is between infrared and ultraviolet light, mainly in the visible spectrum, so its application does not produce new generations of iatrogenic malignancies as in the case of ionizing radiation. The laser is a new scalpel which differs from the metal surgical scalpel (also called "optical knife" and "light scalpel"). In the conclusion authors state that using (CO2) complete success was achieved in treatment of the following skin lesions: common viral warts, senile keratosis, seborrhoeic keratosis, plantar viral warts, papillomas, capillary telangiectasias of the face, hemangiomas, juvenile viral warts of the face, ingrown nails, condyloma acuminata, pendular fibromas, xanthelasmas, atheromas, pyogenic granulomas, keratoacanthomas, tattooed skin and basocellular epitheliomas.     

Radiotherapy in the multimodal treatment of esophageal carcinoma. A review

BACKGROUND: The curative potential of exclusively applied surgery or radiotherapy on esophageal carcinoma is exhausted. The 5-year survival rate of surgically treated esophageal carcinoma is stagnant at 20 to 30%, that for radiotherapeutically treated esophageal carcinoma at < or = 10%. The unchanged bad prognoses motivate the search for multimodal therapeutical concepts in order to improve the results of basic therapies. METHOD, RESULTS AND CONCLUSIONS: While neither perioperative radiotherapy nor perioperative chemotherapy were able to improve the treatment results significantly, a progress in the field of primary and preoperative radiochemotherapy emerges. On locally restricted tumors the latest findings show that a simultaneous radiochemotherapy with Cisplatin is more effective than radiotherapy alone. 20 to 30% histologically verified complete remissions can be reached through preoperative radiochemotherapy. These results will influence future treatment concepts. Brachytherapy can be taken into consideration in highly palliative situations as exclusive method of treatment or for support of laser treatment or bouginage for removal of stenosis. As the number of clinically controlled studies is not sufficient the importance of the brachytherapy boost for potentially curative intentions is not yet clear. Up to now the intraluminal hyperthermia is a underestimated method for improving the results of radiotherapy. Our overview summarizes all presently published randomized studies and relevant phase I/II-studies.     

Future treatment options for haematological malignancies

This paper is the last in a series looking at haematological malignancies. It pinpoints where we are now in the treatment of leukaemias before discussing current and future developments.     

Topical silicone gel sheeting in the treatment of hypertrophic scars and keloids. A dermatologic experience

BACKGROUND: Topical silicone gel sheeting has been used successfully in the management of hypertrophic and keloid scars resulting from thermal burn wounds. METHODS: An open-labelled approach using the silicone gel sheets was performed using hypertrophic and keloid scars secondary to surgical procedures or traumatic insults. RESULTS: The silicone gel sheets resulted in moderate improvement in scar thickness, scar color and was noted to be effective to some degree in all tested. The material was easy to use and painless. CONCLUSION: Topical silicone gel sheeting is an effective method for the treatment of hypertrophic and keloid scars and may be considered useful in the treatment of these difficult cutaneous lesions.     

Malignant melanoma from the dermatologic perspective

Early recognition and treatment of thin cutaneous melanomas (stages Ia and Ib) have contributed to a decreased case-fatality rate during the past several decades. The only known preventable risk factor for melanoma is sun protection in childhood, which directly affects the number of melanocytic nevi developing in an adult. Additional risk factors, clinical features, and the malignant potential of precursor lesions are discussed. The four major clinicopathologic subtypes of melanoma are described with recommendations for appropriate biopsy techniques for suspected melanoma. Nationwide skin cancer screenings by dermatologists and greater public awareness of the warning signs of melanoma have enhanced detection of early melanoma and have promoted chances for a cure.     

Basic principles in local dermatologic therapy

The vehicle or ointment base plays an important role in dermatological local treatment. This is true from a therapeutic point of view and with respect to quality of life as well. Vehicles exert pronounced effects on the epidermis; these effects include hydration, lubrication, drying, skin smoothness, occlusion and protection. The vehicle controls the release and penetration, and ultimately the bioavailability, of the dermatological active ingredients. An overly simplified rule of thumb is that a deep-layer effect is enhanced by increasing occlusion. Unfortunately, no uniform classification system exists. Frequently, users of topical applied products are confused by the non-uniform, and in some cases erroneous, vehicle designations. In particular, different names are used to describe the lipophilic emulsion systems. It would be important to consistently use the official designations here: hydrophilic cream or lipophilic (hydrophobic) cream or ointment. Dermatological pastes are also often misleading designated, without any further distinctions, as a uniform occlusive system. For practical applications, attention must be paid in particular to the different indications for hydrophilic and lipophilic vehicles. Hydrophilic, aqueous bases are to be used for acute lesions and seborrhoeic skin, fatty or oily lipophilic systems for dry hyperkeratotic lesions and sebostatic skin. The cosmetic acceptance of a vehicle has a direct impact on both compliance and therapeutic effect. More attention should be paid to these factors. Adverse reactions caused by single components of the vehicle are not unusual. If a lesion does not respond to local treatment, the diagnosis should be reconsidered; moreover, the vehicle and its components should be investigated for possible incompatibility reactions.     

Radiotherapy alone versus neo-adjuvant chemotherapy and irradiation in the treatment of carcinoma of the cavum

Radiation therapy is the usual treatment for nasopharyngeal carcinoma. However, in recent years the use of neoadyuvant chemotherapy in the treatment of local and regionally advanced carcinoma has been investigated. We report the results of a retrospective study of two treatments used in our center. The study included 68 patients: 34 (group A) who received radiotherapy alone and 34 (group B) who received neoadyuvant chemotherapy before radiotherapy. In group A, 70.6% achieved a complete clinical response: 23.5% relapsed: 5 patients presented distant metastases. Survival rates at 5 and 10 years were 53% and 27% respectively; the disease-free survival was 71.4% at 5 years and 54% at 10 years. In group B, the complete clinical response rate to neoadyuvant chemotherapy was 35.3%, which increased to 73.5% when the treatment was complemented with radiotherapy. The relapse rate was 14.7%; the survival rates at 5 and 10 years were 49.5% and 49%, respectively; and the disease-free survival was 77.2% at 5 and 10 years.     

Radiotherapy in the adjuvant therapy of rectal cancer: comparison of two treatment schedules

From 1988 to 1991 54 patient with carcinoma of the distal part of the rectum were cured in our Department. These patients were divided into two groups (similar with regard to sex, age and advance of disease). In group I (28 patients) abdomino-perineal resection was performed, accompanied (according to histo-pathological indications) by adjuvant radiotherapy to maximal dose 6000 cGy. In group II such procedure was preceded by "short" radiotherapy (4 x 500 cGy). Local recurrence rate was 17.8% in group I and 11.5% in group II. CONCLUSIONS: Preoperative radiotherapy (for example "short" schedule 4 x 500 cGy) may decrease number of local recurrences after abdomino-perineal resections in rectal cancer cases. This procedure effects no technical problems and complications during and after operations.     

Radiotherapy treatment planning of brain tumours using MRI alone

MRI of the brain can provide images of very high quality revealing detailed information especially concerning the extent of abnormalities. As such MRI has great potential in the radiotherapy (RT) planning of brain tumours. However MRI has rarely been used alone as the basis for treatment planning primarily due to concern over potential geometric distortions. Treatment planning using MRI has therefore usually been carried out in conjunction with CT images. This work demonstrates that geometric distortions can be minimized by using a relatively small field-of-view, an increased receiver bandwidth, and a fast spin echo acquisition sequence, and that it is thus possible to perform RT planning using MRI.     

Fludarabine. An update of its pharmacology and use in the treatment of haematological malignancies

Fludarabine is an antineoplastic agent which has been studied in patients with a variety of lymphoproliferative malignancies. Clinical evidence from comparative studies in chronic lymphocytic leukaemia (CLL) suggests that fludarabine is at least as effective as CAP (cyclophosphamide, doxorubicin and prednisone) or CHOP (cyclophosphamide, vincristine, doxorubicin and prednisone) in previously treated or chemotherapy-naive patients and significantly more effective than chlorambucil in terms of response rate and duration and survival in chemotherapy-naive patients. Promising results have also been reported with fludarabine-based combination therapy in the treatment of patients with CLL. In addition, sequential therapy with fludarabine and cytarabine has demonstrated good efficacy in the treatment of acute leukaemias, as has fludarabine monotherapy and combination therapy in low grade non-Hodgkin's lymphoma. A favourable cytoreductive response has been reported in patients with lymphoplasmacytoid lymphoma and in a smaller number of patients with cutaneous T cell lymphomas, CLL of T cell origin or prolymphocytic leukaemia. Recent data also support the use of fludarabine, either as a component of a nonmyeloablative conditioning regimen or in the attainment of minimal residual disease, in patients undergoing peripheral blood stem cell or bone marrow transplantation. The tolerability profile of fludarabine is similar to that of CAP, with the most common adverse events being granulocytopenia, thrombocytopenia, anaemia and infection. Alopecia and nausea/vomiting appear to be less frequent with fludarabine therapy than with CAP although the development of immune cytopenias is more frequent with fludarabine. Severe neurotoxicity has been reported with fludarabine but this is mostly confined to the use of high doses. Clinical experience therefore indicates that fludarabine is an effective and generally well-tolerated antineoplastic agent for the second-line treatment of advanced CLL. Recent data from comparative studies also support the earlier use of fludarabine in the treatment of chemotherapy-naive patients with CLL. Furthermore, results of available studies are increasingly highlighting an important future role for fludarabine in the treatment of acute leukaemias and low grade NHL and possibly other lymphoproliferative disorders, particularly when used as a component of combination chemotherapy.     

Impact of phenotype on treatment and prognosis of laryngeal malignancies

An overview of the impact of the phenotype on treatment and prognosis of different laryngeal malignancies is presented.     

Urate oxidase in prevention and treatment of hyperuricemia associated with lymphoid malignancies

Standard prophylaxis and treatment of malignancy-associated hyperuricemia in the USA has been allopurinol with vigorous hydration, urinary alkalinization and osmotic diuresis. Urate oxidase, the enzyme that converts uric acid to allantoin (a readily excreted metabolite that has 5- to 10-fold higher solubility than uric acid), is an alternative therapy; however, few published findings support this practice. Between February 1994 and December 1996, we administered non-recombinant urate oxidase (Uricozyme) to 126 children with newly diagnosed non-B cell acute lymphoblastic leukemia (ALL) during the first 5 days of chemotherapy with methotrexate, 6-mercaptopurine or both. Their blood levels of uric acid and other indicators of tumor lysis were measured at diagnosis and during treatment and then compared with findings in 129 similarly treated historical controls who had received allopurinol to control hyperuricemia. Clinical responses to urate oxidase were also determined in eight patients with newly diagnosed B cell ALL or advanced-stage non-Hodgkin lymphoma. Patients treated with urate oxidase had rapid and significantly greater decreases in their blood uric acid levels than did the historical controls (median maximal level during treatment, 2.3 vs 3.9 mg/dl, P < 0.001). They also had lower creatinine (0.6 vs 0.7 mg/dl, P = 0.01) and blood urea nitrogen (11 vs 24 mg/dl, P < 0.001) levels. Similar findings were made in the eight cases of B cell ALL or non-Hodgkin lymphoma. None of the patients required dialysis for acute renal failure. Six (4.5%) of the 134 children given urate oxidase had allergic reactions, manifested primarily by urticaria, bronchospasm and hypoxemia. Thus, non-recombinant urate oxidase is a more effective uricolytic agent than allopurinol but is associated with acute hypersensitivity reactions, even in patients without a history of allergy.     

2-Chlorodeoxyadenosine: a newer purine analog active in the treatment of indolent lymphoid malignancies

OBJECTIVE: To review the structure, mechanism of action, pharmacologic features, and clinical trial results of the newer purine analog, 2-chlorodeoxyadenosine (2-CdA). DATA SOURCES AND STUDY SELECTION: English-language medical literature review of more than 70 articles. DATA SYNTHESIS: 2-Chlorodeoxyadenosine is unique compared with traditional antimetabolite drugs in that it is equally active against dividing and resting lymphocytes, which may be especially important in indolent lymphoid malignancies, such as chronic lymphocytic leukemia, because most cells in these disorders are in the resting phase. In patients with alkylator-refractory chronic lymphocytic leukemia who were treated with 2-CdA, 44% achieved a response (4% complete responses, 40% partial responses), and 54%, scored as nonresponders, had a sustained reduction in their peripheral lymphocytosis. Patients with untreated chronic lymphocytic leukemia had an 85% response rate (25% complete responses, 60% partial responses). Patients with previously treated low-grade lymphoma achieved an overall response rate of 43%. The most striking clinical effects of this drug have been seen in hairy cell leukemia, in which a single course of therapy induces complete remissions in 85% of partial remissions in 12%. Activity has also been shown in cutaneous T-cell lymphoma and the myeloid leukemias. CONCLUSIONS: 2-Chlorodeoxyadenosine is a newer purine analog with potent activity in the treatment of indolent lymphoproliferative diseases and illustrates the model for rational drug development.