Thermoradiotherapy for residual microscopic cancer: elective or post-excisional hyperthermia and radiation therapy in the management of local-regional recurrent breast cancer.

A Phase I/II study was undertaken to investigate the efficacy and side effects of combined hyperthermia and radiation therapy in the management of presumed or known microscopic residual tumors. Between February 1985 and March 1991, 262 fields in 89 patients with local-regional recurrent breast cancer were treated with externally administered hyperthermia and radiation therapy. Thirty-eight fields were treated for microscopic residual disease following excisional biopsy of nodular recurrences and 224 fields were treated electively for areas at high risk for local recurrences adjacent to fields with macroscopic residual disease. Mechanically mapped temperatures were monitored throughout the field in all treatments. All patients had at least one follow-up evaluation at three weeks or more following completion of treatment. The majority of the fields were in patients who had had extensive prior therapy including radiation therapy (54%), chemotherapy (71%), and hormonal therapy (51%). All fields received hyperthermia (1-6 treatments: average 1.74) and radiation therapy (average dose: 42.4 Gy); concurrent hormonal therapy was administered in 37% of the treatments and no fields received concurrent chemotherapy. The treatments were well tolerated, no life-threatening complications were noted. Averages for all fields of the minimum, maximum, and average measured interstitial temperatures were 40.2 degrees C, 45.3 degrees C, and 42.8 degrees C, respectively. The three-year actuarial local-control rate for all 262 treated fields was 68%. Parameters characterizing the initial breast cancer, the patient and tumor at the time of hyperthermia, and the treatment were studied in univariate and multivariate analysis for correlation with duration of local control within the hyperthermia treatment field. Parameters in the best five covariate model correlating with the duration of local control included: estrogen receptor status of the initial breast cancer; initial T-stage; time from initial breast cancer to first failure; age at hyperthermia; and concurrent radiation dose (p-value for model less than 0.000001). Six covariate models adding anatomic site of disease, field type, mean minimum temperatures, and mean percent temperatures greater than or equal to 40 degrees C all resulted in improved models. Randomized controlled studies stratifying for these pretreatment parameters are felt warranted to confirm the value of adjuvant hyperthermia in the elective treatment of areas of high risk for local-regional recurrent breast cancer and in fields following surgical excision of recurrent disease, particularly in patients in whom full dose radiation therapy cannot be safely administered.     

The prognostic significance of pre- and posttreatment SCC levels in patients with squamous cell carcinoma of the cervix treated by radiotherapy

Purpose: To investigate the prognostic significance of the pre- and posttreatment serum squamous cell carcinoma antigen (SCC) levels in patients with Stage I-IVA squamous cell carcinoma of the cervix primarily treated by radiotherapy.Materials and Methods: 401 patients with squamous cell carcinoma of cervix primarily treated with radiotherapy (RT) were included in this study. All had preRT, and 249 patients had postRT serum SCC values. The association of pretreatment SCC level with the clinical parameters, including stage, hemoglobin (Hb) level, age, cell differentiation, and lymph node status, was assessed by univariate and multivariate analysis. The prognostic significance of pretreatment SCC level and these clinical parameters were evaluated. The impact of postRT residual induration and SCC levels on survival was analyzed.Results: 1. PreRT SCC level strongly correlated with stage. After controlling for stage, only SCC levels higher than 10 ng/ml were associated with enlarged lymph nodes shown in CT scan. No association of preRT SCC level with other clinical parameters was found. 2. SCC level higher than 10 ng/ml, but not between 2–10 ng/ml, had significant impact on survival in a multivariate analysis. Stage, Hb levels (<10 g/dl) and positive lymph node shown by CT scan were also independent prognostic factors for survival. No significant difference in failure pattern in terms of local and/or distant sites was found in patients with different SCC levels. 3. Patients with residual induration and/or persistently elevated SCC level at 2–3 months after RT had a significantly higher incidence of treatment failure. Persistently elevated SCC level is a stronger predictor for treatment failure than residual induration by pelvic examination, and is associated with a higher incidence of distant metastasis. One third of patients with initial SCC level higher than 10 ng/ml had persistently elevated SCC.Conclusion: Pretreatment SCC levels higher than 10 ng/ml are an independent predictor for poor prognosis in patients included in this study, and can be used as one of the prognostic factors for selection of patients for intensive treatment. Persistently elevated SCC levels after RT is a strong predictor for treatment failure. A combination of clinical pelvic examination and SCC levels provides useful information for the need of further work-up and management.     

Fractionation sensitivity and dose response of late adverse effects in the breast after radiotherapy for early breast cancer: long-term results of a randomised trial.

BACKGROUND AND PURPOSE: Unlike squamous carcinomas, breast adenocarcinoma may be as sensitive to fraction size as late dose-limiting normal tissues. If so, fewer larger fractions would be as safe and effective as regimens based on 2.0 Gy fractions. The first step is to test the effects of radiotherapy fractions >2.0 Gy on late normal tissue responses in the breast after tumour excision and radiotherapy for early breast cancer. PATIENTS AND METHODS: One thousand four-hundred and ten women with T1-3 N0-1 M0 invasive breast cancer were randomised between 1986-98 into one of three radiotherapy regimens after local tumour excision of early stage breast cancer; 50 Gy in 25 fractions (F) vs two dose levels of a test schedule giving 39 or 42.9 Gy in 13 F over 5 weeks. Fraction sizes were 2.0, 3.0 and 3.3 Gy, respectively. The primary endpoint was late change in breast appearance compared to post-surgical appearance scored from annual photographs blinded to treatment allocation. Secondary endpoints included palpable breast induration (fibrosis) and ipsilateral tumour recurrence. RESULTS: After a minimum 5-year follow up, the risk of scoring any change in breast appearance after 50 Gy/25 F, 39 Gy/13 F and 42.9 Gy/13 F was 39.6, 30.3 and 45.7%, from which an alpha/beta value of 3.6 Gy (95% CI 1.8-5.4) is estimated. The alpha/beta value for palpable breast induration was 3.1 Gy (95% CI 1.8-4.4). CONCLUSIONS: An alpha/beta value of around 3 Gy for late normal tissue changes in the breast is derived from the estimated equivalence of 41.6 Gy in 13 fractions and 50 Gy in 25 fractions over 5 weeks, in line with trial predictions.     

Hyperthermia and radiation therapy of local-regional recurrent breast cancer: prognostic factors for response and local control of diffuse or nodular tumors

Over the past decade, hyperthermia has been extensively studied as an adjuvant to radiation therapy in the management of local-regional metastases from adenocarcinoma of the breast. A retrospective review of our experience from July 1982 to January 1990 identified 241 fields in 89 patients which satisfied the following criteria: biopsy confirmation of recurrent or metastatic adenocarcinoma of the breast; involvement of the chest wall and/or regional lymph nodes with diffuse or nodular metastases; treatment which included radiation therapy and externally administered hyperthermia during which mechanically-mapped and/or multipoint normal tissue and intratumoral temperatures were monitored; and at least one follow-up evaluation at 3 weeks or more after completion of treatment. The majority of fields were in patients who had extensive prior treatment including radiation therapy (68%), chemotherapy (86%), and hormonal therapy (58%). Treatment consisted of radiation therapy (average dose: 39.88 Gy) and hyperthermia (1-12 treatments; average 3.12); concurrent chemotherapy or hormonal therapy were also administered in 3% and 32% of the fields, respectively. Parameters characterizing the initial breast cancer, the patient and tumor at the time of hyperthermia, and the treatment were studied in univariate and multivariate analyses with complete response rate at the time of maximum tumor regression and duration of local control as endpoints. The treatments were well tolerated with no life-threatening complications noted. The means for all fields of the mean minimum, mean maximum, and mean average measured intratumoral temperatures were 40.3 degrees C, 44.6 degrees C, and 42.4 degrees C, respectively. At 3 weeks following completion of radiation therapy, response rates were: complete response (52%), partial response (8%), no response (17%), and continuing regression (monotonic regression to less than 50% of initial volume) was noted in 22% of the fields. At the time of maximum tumor regression local control was noted in 72% of the fields. Five parameters correlated with higher complete response in univariate and multivariate analysis: lower T-stage of the initial breast cancer; at the time of hyperthermia age less than 50 years, Karnofsky status greater than 95%, and the absence of distant metastases; and the use of concurrent hormonal therapy. The absence of a family history of breast cancer and concurrent radiation dose greater than or equal to 25 Gy significantly correlated with higher complete response in the univariate but not in the best multivariate models.(ABSTRACT TRUNCATED AT 400 WORDS)     

体外加温43℃对Tca-8113细胞形态及结构的影响

目的:研究体外加温43℃对舌癌细胞株形态及超微结构的影响,探讨热疗的作用机理。方法:对舌癌细胞株Tca-8113进行体外43℃加温,通过光镜、透射电镜及MTT法进行观察,研究加温后细胞形态、超微结构及增殖活性的变化。结果:外加温43℃后,细胞形态趋向良性分化,胞质内成熟细胞器增多,出现微丝,增殖活性降低并与加热时间成正比。结论:外加温43℃能使肿瘤细胞趋于成熟,生长速度减慢,恶性程度降低,侵袭、转移力减弱,达到治疗肿瘤的目的。     

Parameters predictive for complications of treatment with combined hyperthermia and radiation therapy.

Pretreatment and treatment related factors were reviewed for 996 hyperthermia sessions involving 268 separate treatment fields in 131 patients managed with hyperthermia for biopsy confirmed local-regionally advanced or recurrent malignancies to ascertain parameters associated with the development of complications. A subset of 249 fields were identified in which multipoint or mapped temperature data were available for at least one treatment session per field. A total of 198 fields involved superficially located tumors (less than or equal to 3 cm from the surface), whereas 51 fields involved more deeply located tumors. Most of these patients had received extensive prior therapy: 77% had surgery, 75% chemotherapy, 65% radiation therapy and 28% hormonal therapy. They were treated with hyperthermia in conjunction with radiation therapy (244 fields) or hyperthermia alone (5 fields). The hyperthermia treatment objectives were to elevate intratumoral temperatures to a minimum of 43.0 degrees C for 45 minutes while maintaining maximum normal tissue temperatures to less than or equal to 43 degrees C and maximum intratumoral temperatures to less than or equal to 50 degrees C. The hyperthermia was given within 30 to 60 minutes following radiation therapy without the administration of additional analgesics. Hyperthermia treatment regimens using radiative electromagnetic, ultrasound, or radiofrequency interstitial techniques were individualized, with 3 to 4 days between hyperthermia treatments and an average of 3.6 treatments (range 1-14; standard deviation 2.2) utilized per field. A total of 38 complications in 33 treatment fields were noted; an incidence of 27/198 (13.6%) for fields with superficially located tumors, and 6/51 (11.8%) in fields with more deeply located tumors. Univariate analyses demonstrated statistically significant correlations between the maximum tumor temperature (p = 0.0005), average of the maximum tumor temperatures (p = 0.0006), the average of the % tumor temperatures greater than 43.5 degrees C (p = 0.0071), and the average number of hyperthermia treatments (p = 0.033), with the development of complications. The average of the maximum measured tumor temperature for fields without complications was 44.6 degrees C compared with 45.9 degrees C for fields with complications. The complication rate increased from 7.5% (9/120) in fields that received one or two hyperthermia treatments to 18.6% (24/129) in fields that received greater than two hyperthermia treatments. Multivariate logistic regression analyses revealed the best bivariate model predictive of the development of complications included average of the maximum tumor temperature and the number of treatments per field (p = 0.00012 for the bivariate model).(ABSTRACT TRUNCATED AT 400 WORDS)     

A complete response of an advanced oesophageal carcinoma treated with hyperthermic chemotherapy: a case report.

A 56-year-old Japanese man with an advanced squamous cell carcinoma in the middle oesophagus was treated with a combination of hyperthermia, intravenous infusion of cisplatin (CDDP) and oral administration of oily bleomycin(BLM)-polyacrylate paste. After performing six sessions of hyperthermia treatment conducted at 42-45 degrees C for 30 min with 150 mg of CDDP and 180 mg of BLM, a subtotal oesophagectomy and lymph node dissection were performed. A histopathological study of the resected specimen showed no residual viable cancer cells either in the oesophagus or in the dissected lymph nodes. There were no side effects or perioperative complications and the patient is now healthy and leading a normal life 10 months after operation without undergoing any further treatment, at the time of writing. The effect of small amounts of CDDP and the oral application of oily BLM were thought to be strongly enhanced by hyperthermia in the treatment of oesophageal squamous carcinoma, and this regimen is therefore recommended as a safe and effective strategy, especially for preoperative treatment.     

A complete response of an advanced oesophageal carcinoma treated with hyperthermic chemotherapy: a case report

A 56-year-old Japanese man with an advanced squamous cell carcinoma in the middle oesophagus was treated with a combination of hyperthermia, intravenous infusion of cisplatin (CDDP) and oral administration of oily bleomycin(BLM)-polyacrylate paste. After performing six sessions of hyperthermia treatment conducted at 42–45°C for 30 min with 150 mg of CDDP and 180 mg of BLM, a subtotal oesophagectomy and lymph node dissection were performed. A histopathological study of the resected specimen showed no residual viable cancer cells either in the oesophagus or in the dissected lymph nodes. There were no side effects or perioperative complications and the patient is now healthy and leading a normal life 10 months after operation without undergoing any further treatment, at the time of writing. The effect of small amounts of CDDP and the oral application of oily BLM were thought to be strongly enhanced by hyperthermia in the treatment of oesophageal squamous carcinoma, and this regimen is therefore recommended as a safe and effective strategy, especially for preoperative treatment.     

Double-blind, placebo-controlled, randomised phase II trial of IH636 grape seed proanthocyanidin extract (GSPE) in patients with radiation-induced breast induration.

BACKGROUND AND PURPOSE: Tissue hardness (induration), pain and tenderness are common late adverse effects of curative radiotherapy for early breast cancer. The purpose of this study was to test the efficacy of IH636 grape seed proanthocyanidin extract (GSPE) in patients with tissue induration after high-dose radiotherapy for early breast cancer in a double-blind placebo-controlled randomised phase II trial. PATIENTS AND METHODS: Sixty-six eligible research volunteers with moderate or marked breast induration at a mean 10.8 years since radiotherapy for early breast cancer were randomised to active drug (n = 44) or placebo (n = 22). All patients were given grape seed proanthocyanidin extract (GSPE) 100 mg three times a day orally, or corresponding placebo capsules, for 6 months. The primary endpoint was percentage change in surface area (cm(2)) of palpable breast induration measured at the skin surface 12 months after randomisation. Secondary endpoints included change in photographic breast appearance and patient self-assessment of breast hardness, pain and tenderness. RESULTS: At 12 months post-randomisation, > or =50% reduction in surface area (cm(2)) of breast induration was recorded in 13/44 (29.5%) GSPE and 6/22 (27%) placebo group patients (NS). At 12 months post-randomisation, there was no significant difference between treatment and control groups in terms of external assessments of tissue hardness, breast appearance or patient self-assessments of breast hardness, pain or tenderness. CONCLUSIONS: The study failed to show efficacy of orally-administered GSPE in patients with breast induration following radiotherapy for breast cancer.     

Re-irradiation and hyperthermia for recurrent breast cancer in the orbital region: a case report.

Based on the good results of re-irradiation plus hyperthermia in breast cancer recurrences on the chest wall, it was decided to offer similar treatment to a patient with recurrent metastatic breast cancer in the orbital region. A female patient was diagnosed in 1997 with breast cancer stage T4N0M0. She was treated with six neo-adjuvant chemotherapy courses and mastectomy, followed by hormonal treatment. In December 1998, she was diagnosed with metastatic disease in the medial upper quadrant of the left orbit. This was excised, followed by 40 Gy radiotherapy. Nine months later, the tumour had recurred in the left orbit at the margin of the radiotherapy field. This again was treated with surgery, followed by 30 Gy radiotherapy. Two months thereafter, the eyelid tumour progressed and hormonal therapy was changed, without an effect on the eyelid tumour. Screening gave no evidence of tumour activity elsewhere. The patient preferred treatment with re-irradiation plus hyperthermia to a surgical approach. Eight fractions of 4 Gy were given in 4 weeks, combined with once weekly hyperthermia. One week after treatment, the tumour had regressed completely. The patient died 22 months following treatment. Until last follow-up, a few weeks before death, the patient mentioned a dry left eye for which she used eyedrops, an unchanged vision and no further difficulties. On examination, there was epilation of the eyelids, a slight conjunctival oedema, no subcutaneous fibrosis and no evidence of tumour regrowth. For this patient, a surgical approach would have resulted in loss of the left eye. Toxicity of re-irradiation plus hyperthermia might lead to either a loss of vision or a delayed loss of her left eye due to treatment-induced toxicity. The chosen local treatment resulted in a very good palliative effect, which lasted for the patient's remaining lifetime of 22 months.     

Prospective randomized study of hyperthermia combined with chemoradiotherapy for esophageal carcinoma

From January 1988 to June 1992, 66 patients with resectable squamous cell carcinoma of the thoracic esophagus underwent preoperative adjuvant therapy. These patients were prospectively divided into two treatment groups; 32 were treated with radiofrequency wave local hyperthermia combined with chemoradiotherapy (hyperthermochemoradiotherapy; HCR), while the remaining 34 patients were treated with chemoradiotherapy alone (CR). There were no procedural complications in either group and the postoperative mortality was zero. In the HCR group, no viable cancer cells were found within the entire 5 mm-width slices of the resected specimen in eight patients (25%), while only two (5.9%) in the CR group (P < 0.05) demonstrated no viable cancer cells. The cumulative 3-year survival rate was 50.4% in the HCR group and 24.2% in the CR group. The present prospective trial demonstrated that the addition of hyperthermia to chemoradiotherapy resulted in a better local control and an improved long-term survival when treating patients with advanced esophageal carcinoma. © 1995 Wiley-Liss, Inc.     

The role of socio-economic status in the decision making on diagnosis and treatment of oesophageal cancer in The Netherlands

In the United States (USA), a correlation has been demonstrated between socio-economic status (SES) of patients on the one hand, and tumour histology, stage of the disease and treatment modality of various cancer types on the other hand. It is unknown whether such correlations are also involved in patients with oesophageal cancer in The Netherlands. Between 1994 and 2003, 888 oesophageal cancer patients were included in a prospective database with findings on the diagnostic work-up and treatment of oesophageal cancer. Socio-economic status of patients was defined as the average net yearly income. Linear-by-linear association testing revealed that oesophageal adenocarcinoma was more frequently observed in patients with higher SES and squamous cell carcinoma in patients with lower SES (P=0.02). Multivariable logistic regression analysis showed no correlation between SES and staging procedures and preoperative TNM stage. The adjusted odds ratio (OR) for stent placement was 0.82 (95% CI 0.71-0.95), indicating that with an increase in SES by 1200 [euro], the likelihood that a stent was placed declined by 18%. Patients with a higher SES more frequently underwent resection or were treated with chemotherapy (OR: 1.15; 95% CI 1.01-1.32 and OR: 1.16; 95% CI 1.02-1.32, respectively). Socio-economic factors are involved in oesophageal cancer in The Netherlands, as patients with a higher SES are more likely to have an adenocarcinoma and patients with a lower SES a squamous cell carcinoma. Moreover, the correlations between SES and different treatment modalities suggest that both patient and doctor determinants contribute to the decision on the most optimal treatment modality in patients with oesophageal cancer.     

Squamous cell carcinoma of the breast: clinico-pathologic implications and outcome.

AIMS: Pure squamous cell carcinoma (SCC) of the breast is a rare tumour and little is known about long-term outcome. We report our experience of a consecutive series of patients. METHODS: All patients with SCC treated at our institution between 1970 and 2001 were included. The pathological features, outcome and prognosis were studied. RESULTS: Eleven patients were identified. The median age was 55 (38-90) years and median follow-up was 62 (3-332) months. Four tumours were T1, three were T2 and three were T3 (one tumour size was unknown). There were seven poorly differentiated and three moderately differentiated SCC. Tumour grade could not be assessed in one patient. Primary treatment was mastectomy in six patients, wide local excision in four patients and radiotherapy in one patient. There was lymph node (LN) involvement in two patients. Oestrogen receptor status was assessed in seven patients and only one tumour was positive. Adjuvant chemotherapy was given to three patients and five patients received adjuvant radiotherapy. Two patients developed local recurrence at 5 and 12 months and three patients developed distant metastasis at 2, 36 and 306 months. Three patients were treated with chemotherapy at recurrence. Three patients have died of the disease, two are alive with disease and six remain well. The 2- and 5-year overall survival was 80% (SE=13%) and 67% (SE=16%) respectively. Large tumour size and positive LN status were prognostic indicators of poor outcome. CONCLUSION: SCC of the breast adopts an aggressive course with outcome comparable to poorly differentiated breast adenocarcinoma.     

Pretreatment and treatment factors associated with improved outcome in squamous cell carcinoma of the uterine cervix: a final report of the 1973 and 1978 patterns of care studies

The Patterns of Care Study (PCS) conducted two national surveys of patients treated in 1973 and 1978 for squamous cell cancer of the uterine cervix. In addition, a survey of patients treated in 1973 from selected large facilities was conducted to establish outcome with "optimal" radiotherapy. The large facility survey consistently reported improved outcome compared to both national average surveys when analyzed by stage and other significant pretreatment factors. That improved outcome was associated with the paracentral (PCS point A) dose and the use of intracavitary irradiation. In this study, we report the pretreatment and treatment factors associated with improved outcome in squamous cell carcinoma of the uterine cervix by analysis of the 1973 and 1978 PCS data. Pretreatment factors associated with improved pelvic control in multivariate analysis include higher Karnofsky Performance Status (KPS) (Stage I and II), older age (Stage I and II), unilateral parametrial involvement (Stage IIB), and unilateral sidewall involvement (Stage III). The only treatment factor associated with improved pelvic control in multivariate analysis is the use of intracavitary irradiation. However, a dose response for infield pelvic control was demonstrated only in Stage III cervix cancer with the highest rate of pelvic control with paracentral (PCS point A) dose greater than 8500 cGy. Multivariate analysis revealed that unilateral parametrial involvement for Stage IIB and unilateral sidewall involvement for Stage III are significant positive prognostic factors with respect to survival after treatment with radiotherapy. No FIGO substage significantly affected survival after radiotherapy. Although FIGO staging is the single most important pretreatment prognostic factor with respect to survival and infield pelvic failure, FIGO substaging deserves reappraisal and further refinement. Major complications were seen in only 9.5% of patients treated with radiotherapy and were stage but not survey related. There is a significant relationship between PCS point A dose and complications with the highest rate of complications for PCS point A dose greater than 8500 cGy. A significant relationship between lateral (external iliac lymph nodes or PCS point P) dose and major complications is also found, and doses greater than 5000 cGy are associated with a significant increase in complications. The PCS has established two sequential national benchmarks of treatment outcome for squamous cell carcinoma of the uterine cervix treated with radiotherapy with respect to survival, infield pelvic control, and complications.(ABSTRACT TRUNCATED AT 400 WORDS)     

Prognostic factors in metastatic malignant melanoma treated with combined radiation therapy and hyperthermia

From May 1981 to September 1991, 38 patients with metastatic malignant melanoma were treated with combined radiation therapy and hyperthermia to a total of 97 hyperthermia treatment fields. Prior treatments to these sites included surgery (31 patients, 76 fields), chemotherapy (18 patients, 54 fields), immunotherapy (14 patients, 42 fields) and radiation therapy (7 patients, 13 hyperthermia fields). Hyperthermia was given to fields located in the head and neck region, trunk and extremities in 30, 45 and 22 cases, respectively. Nodular-diffuse tumours were present in 86 fields while 11 fields were treated for microscopic residual tumour deposits. Concurrent radiation therapy was given in 180–400 cGy per fraction, 2–5 times per week for a mean total dose of 4098 cGy per field. Hyperthermia treatments were delivered using either microwave or ultrasound devices (286 and 48 treatments, respectively) with a mean (range) of 3. 4 (1–14) hyperthermia treatments per field for a mean (range) of 43 (10–70) min per field. Patients (n = 34; 84 fields) were available for follow-up for a mean (range) of 14–6 (0–4-82.5) months. At 3 weeks post-treatment, 34 fields had complete, ongoing, or partial responses; 39 fields had no response; and there were no recurrences in the 11 fields treated for microscopic residual disease. Local control was maintained in 31% (26/84) fields with a mean follow-up of 14.6 months. At 36 months, five patients remained alive with complete control of their treated local disease. Statistical analyses revealed that patients with soft tissue metastases only, who were older at the time of hyperthermia, had a longer time between initial diagnosis and hyperthermia treatment, received a higher dose of radiation, had no previous chemotherapy, and had small tumour volumes, had a higher initial response. Multivariate analyses revealed that the three-covariate model including time interval between initial diagnosis and hyperthermia treatment, previous chemotherapy, and metastases to soft tissue only, best predicted response. The results of the investigation support the continued study of combined radiation therapy and hyperthermia treatments for selected patients with metastatic melanoma, and indicate that long-term survival can occasionally be obtained with this approach.     

Effects of fibroblast growth inhibitor on proliferation and metastasis of oral squamous cell carcinoma

Development of a new therapeutic approach to improve the prognosis of high grade invasion of oral squamous cell carcinoma is needed. To elucidate the effect of a fibroblast inhibitor (tranilast), we investigated the proliferation and metastasis of oral squamous cell carcinoma in a mouse model. The effect of tranilast on tumour growth, lymph node metastases, microvessel density, and the proliferating cell nuclear antigen (PCNA) labelling index of oral squamous cell carcinoma implanted into the tongue of nude mice was evaluated. Tumour growth and the incidence of cervical lymph node metastases were significantly suppressed by the administration of tranilast. The amount of fibrous tissue, the microvessel density, and the PCNA labelling index of tumour were also significantly reduced. Administration of a fibroblast inhibitor may well be clinically effective for the treatment of oral squamous cell carcinoma.     

Adriamycin, cisplatin and etoposide combination chemotherapy in non-small cell lung cancer]

Nineteen patients with non-small cell lung cancer (eight patients with adenocarcinoma, nine patients with squamous cell carcinoma, one patient with large cell carcinoma and one patient with sarcoma) who had not received previous chemotherapy were treated with a combination of adriamycin (30 mg/m2, i.v., on day 1), cisplatin (80 mg/m2, i.v., on day 1) and etoposide (70 mg/m2, i.v., on day 1-5). This chemotherapy regimen was repeated as long as possible for patients in whom PR was induced. Among all patients, CR was induced in none and 6 showed a PR (response rate 32%). However, 4 (56%) squamous cell carcinoma patients also showed PR. The median response duration in 6 PR patients was 28 weeks, and the median survival time in all patients was also 28 weeks. Mild to severe hematologic toxicities were induced and one patient died during myelosuppression. However almost all cases were reversible. Other toxicities included alopecia, nausea/vomiting, diarrhea, stomatitis, peripheral neuropathy and myocardial infarction which were reversible and manageable. The APVp therapy may be a valuable regimen for non-small cell lung cancer, especially squamous cell carcinoma.     

Lip cancer experience in Mexico. An 11-year retrospective study

Lip cancer is the most frequent malignant neoplasm of the oral cavity; however, there is no information available on the incidence of this type of cancer in Mexico. This study provides information about the clinico-pathological features of lip cancer patients admitted at a cancer hospital in Mexico City during an 11-year period and describes the treatment modalities performed and their results. A total of 113 patients were studied. There were 74 men (65.5%) and 39 women (34.5%), ranging in age from 14 to 106 years (mean 70 years). In 53 cases (46.9%) an association was found between the disease and chronic sun exposure. Additionally, positive smoking antecedents were recorded in 58 cases (51.3%). As 15 patients were followed for less than 1 month, they were excluded for further analysis. There were 82 cases (83.7%) of squamous cell carcinoma, 10 (10.2%) basal cell carcinomas, and one case (1%) each of adenocarcinoma NOS, melanoma, adenoid cystic carcinoma, Merkel cell carcinoma, lymphoepithelioma and angiosarcoma. We observed an incidence of malignant neoplasms in the upper lip of 33.7%, which is higher than most of the published series and may be due to the fact that in this series we included all histological types of lip cancers. Fifty percent of the cases were found in stages III and IV. Cervical lymph node metastases were found in 21% of patients with no previous treatment, and they developed in 5.3% after treatment. Our data suggest that tumoral size is directly related to the possibility of developing node metastases, as none of them occurred in patients T1, whereas 10 (62.5%) of the patients in T4 presented them. Seven deaths were documented (7.1%), five of which corresponded to squamous cell carcinoma, one to Merkel cell carcinoma, and one to adenocarcinoma. Deaths were directly related to the disease in six cases, and one patient died due to surgical complications. Distant metastases were found in only two patients, one of which coursed with an adenocarcinoma and the other with a Merkel cell carcinoma. Based on the present results, we suggest that the differences encountered with respect to other series, particularly the higher incidence found in women, the frequent presentation of this type of neoplasms in the upper lip, the wide variety of histopathological diagnoses and the high frequency of cases with cervical lymph node affection, should lead us to search for multi-modal treatment alternatives in this population.     

Bilateral breast carcinoma treated with definitive irradiation

From 1977 to 1987, 30 women were treated with definitive irradiation following breast-conserving surgery for bilateral carcinoma of the breast for a total of 60 treated breasts. Eleven women presented with concurrent bilateral carcinoma, and 19 women had sequential bilateral carcinoma. Pathologic axillary staging was performed in 51 of the 60 treated breasts. A total dose of greater than or equal to 6,000 cGy was delivered from breast tangential irradiation plus an electron or Iridium boost to 95% (57/60) of the treated breasts. A third field was used to treat the regional axillary and supraclavicular lymph nodes bilaterally in three women (10%) and unilaterally in ten women (33%). Tangential fields were matched at midline in 17 patients, and in ten patients, the tangential fields overlapped by up to 3 cm on skin. In two patients, the tangential fields were matched to an internal mammary nodal field, and in one patient, tangential fields were matched to a mediastinal field given for postoperative radiotherapy for lung cancer. For the overall group of 30 patients, the 5-year actuarial NED survival following treatment of the first breast cancer was 79%, and the 5-year actuarial relapse-free survival was 72%. For the 60 treated breasts, the 5-year actuarial local failure rate was 6%. An analysis of complications and cosmesis showed results similar to previously reported results for unilateral breast cancer. These results show that definitive irradiation following breast-conserving surgery for patients with bilateral breast cancer can technically be delivered with low complication rates and with acceptable survival and local control rates. Definitive irradiation should be considered as an acceptable alternative treatment to bilateral mastectomy for appropriately selected patients with concurrent or sequential bilateral early stage carcinoma of the breast.