Prognostic value of S-100 immunostaining in tumour cells of non-small cell lung cancer.

S-100 protein expression is present in various malignant tissues, yet its prognostic relevance is debatable. The aim was to assess in non-small cell lung cancer (NSCLC) patients' prognostic value of S-100 protein considered alone or in relation with other variables. Tumour samples taken from 86 NSCLC patients during resection were assayed for S-100 protein expression with the use of polyclonal DAKO ZO311 antibody. S-100 expression was found in 32 cases (37%). Positive staining was not correlated with clinical characteristics including age, sex, pathology type of tumour, stage and cigarette smoking. There was a tendency for simultaneous expression of S-100 and P53 protein (p=0.06). A median survival rate for the entire group was 2.3 years (95% CI, 0.9-3.6 years). The median and 5-year survival of patients with positive staining for S-100 protein was 1.5 years and 25%, respectively, compared with 3.0 years and 35%, respectively, in the S-100 negative group (p=0.17). In the final model of a multivariate analysis, S-100 protein expression in tumour cells was associated with significantly decreased survival (p=0.005). S-100 protein expression in tumour cells seems to be an independent predictor of poor prognosis in NSCLC patients.

Chemotherapy with mitomycin c, ifosfamide, and cisplatin for recurrent or persistent cervical cancer.

The efficacy and toxicity of mitomycin C (MMC), ifosfamide, and cisplatin in cervical cancer were evaluated. Between January 1997 and August 2003, 46 patients with locally recurrent, persistent, or disseminated cervical cancer were treated with MMC 6 mg/m(2), ifosfamide 3 g/m(2), and cisplatin 50 mg/m(2) (MIC regimen) repeated every 3 weeks (maximum six cycles). In eight patients (17%), the tumor involved the pelvis alone, in 11 (24%) the pelvis and extrapelvic sites, and 27 (59%) had only distant lesions. A total of 213 MIC cycles were administered (median six cycles per patient). Of the 44 evaluable patients, the overall response rate was 34% (9% complete and 25% partial responses). Median progression-free interval was 6 months (95% confidence interval [CI], 4-7 months), and overall survival was 10 months (95% CI, 6-14 months). Objective response was obtained in two patients (11%) with pelvic relapse within previously irradiated area and in 13 (50%) of those with extrapelvic lesions (P= 0.01). Leukopenia was seen in 59% of patients (grade 3 in 9%). Nonhematologic side effects were mild and relatively infrequent. In conclusion, MIC regimen provides satisfactory efficacy with acceptable toxicity in advanced cervical cancer patients. Better response is seen in lesions outside of the previously irradiated area.

Sphincter preservation following preoperative radiotherapy for rectal cancer: report of a randomised trial comparing short-term radiotherapy vs. conventionally fractionated radiochemotherapy.

BACKGROUND AND PURPOSE: The aim was to verify whether preoperative conventionally fractionated chemoradiation offers an advantage in sphincter preservation in comparison with preoperative short-term irradiation. PATIENTS AND METHODS: Patients with resectable T3-4 rectal carcinoma without sphincters' infiltration and with a lesion accessible to digital rectal examination were randomised into: preoperative 5x5Gy short-term irradiation with subsequent total mesorectal excision (TME) performed within 7 days or chemoradiation to a total dose of 50.4Gy (1.8Gy per fraction) concomitantly with two courses of bolus 5-fluorouracil and leucovorin followed by TME after 4-6 weeks. Surgeons were obliged to base the type of operation on the tumour status at the time of surgery. RESULTS: Between 1999 and 2002, 316 patients from 19 institutions were enrolled. The sphincter preservation rate was 61% in the 5x5Gy arm and 58% in the radiochemotherapy arm, P = 0.57. The tumour was on average 1.9 cm smaller (P < 0.001) among patients treated with chemoradiation compared with short-term schedule. For patients who underwent sphincter-preserving procedure, the surgeons generally followed the rule of tailoring the resection according to tumour downsizing; the median distal bowel margin was identical (2 cm) for both randomised groups. However, in the chemoradiation group, five patients underwent abdominoperineal resection despite clinical complete response. CONCLUSIONS: Despite significant downsizing, chemoradiation did not result in increased sphincter preservation rate in comparison with short-term preoperative radiotherapy. The surgeons' decisions were subjective and based on pre-treatment tumour volume at least in clinical complete responders.

Conservative treatment for carcinoma of the anus--a report of 35 patients.

Conservative treatment for carcinoma of the anus has become the standard care for this malignancy. In this study we report on our experience with this method with particular emphasis on treatment outcome and acute toxicity. Between April 1991 and February 2002, 35 patients (male/female ratio 0.35) with UICC T(1-i) N(0-3) M(0) squamous cell carcinoma of the anal canal or anal margin were treated with chemo-radiation (31 patients) or radiotherapy alone (4 patients). Three patients had previously undergone local tumor excision with anus preservation. The total tumor dose of 48 to 60 Gy was delivered either by split-course or continuous radiation therapy to the pelvis, followed by a local boost to the primary tumor. Chemotherapy included one or two cycles of mitomycin C (10-15 mg/m(2) day 1) and 5-fluorouracil (450-750 mg/m(2) day 1 to 4 or 5) given during the first and the last part of irradiation. Complete tumor remission was obtained in 26 (76%) out of 34 evaluable patients. Clinically persistent disease was found in five (17%) and three (7%) patients treated with chemo- radiation and radiation alone, respectively. In four of these cases salvage surgery was performed. With a median follow-up of 49 months (range 2-131 months) local recurrence occurred in four patients (12%), and distant metastases - in two (6%). Overall, local treatment failure was observed in twelve patients (35%) including eight with T3 and one with T4 tumor. Local control was maintained until the last follow-up or death in 22 patients (65%). An actuarial 5-year overall and colostomy-free survival rates were 63% (CI, 45-81%) and 45% (CI, 25-64%), respectively. Nineteen patients (54%) experienced acute toxicity, predominantly hematologic and gastrointestinal, and severe effects including one death occurred in 11 patients (31%). Late sequelae including chronic diarrhea, edema of genitalia and legs, impaired sexual activity, and bone fractures were observed in eight patients (24%). Moderate anal stool incontinence occurred in three patients (9%). In conclusion, conservative management of anal carcinoma allows durable colostomy-free survival in a proportion of patients. However, the risk of local failure is relatively high in patients with large primary tumors. Combined chemo-radiation is associated with relatively high rate of acute toxicity.

The feasibility study on continuous 7-day-a-week external beam irradiation in locally advanced cervical cancer: a report on acute toxicity.

PURPOSE: To evaluate the feasibility and toxicity of continuous 7-day-a-week pelvic irradiation with no breaks between external beam irradiation and intracavitary applications. MATERIAL AND METHODS: Between November 1998 and December 1999, 30 patients with FIGO Stage IIB or IIIB cervical cancer were treated with continuous 7-day-a-week pelvic irradiation, to the total Manchester point B dose of 40.0-57.6 Gy. The first 13 patients (group A) were applied a daily tumor dose of 1.6 Gy and the remaining 17 patients (group B)-10.8 Gy. One or two immediate brachytherapy applications (point A dose 10-20 Gy, each) were performed in 28 cases. RESULTS: Two patients did not complete the irradiation due to apparent early progression of disease during the irradiation. Of the remaining 28 evaluable patients 11 (39%) completed treatment within the prescribed overall treatment time and 17 had unplanned treatment breaks. For the latter group overall treatment time ranged from 103 to 122% (mean 114%) and from 103 to 197% (mean 138%) of the planned treatment time for group A and B, respectively. The majority of patients experienced acute toxicity. Severe toxicity (EORTC/RTOG grade 3 and 4), predominantly gastrointestinal, occurred in 5 of the 13 patients in group A, and in 7 of 17 patients in group B. CONCLUSION: The studied regimen was accompanied by considerable toxicity, hindering delivery of irradiation within planned treatment time.

Neural cell adhesion molecule in breast, colon and lung carcinomas.

Neural cell adhesion molecules (NCAM) play an important role in embryogenesis and in some tumors, especially of neuroectodermal origin. In this study, 18 cases of invasive breast carcinoma, 7 cases of sigmoid colon carcinomas and 17 cases of the non-small-cell lung carcinoma were immunostained for NCAM. NCAM expression, usually focal, was observed in some cases only. NCAM was expressed in the membranes, in a fine granular pattern. In 3 cases of breast cancer cytoplasmic localisation of NCAM was also observed, which may suggest its cytoplasmic formation. Furthermore, in 3 cases expression of NCAM in histologically normal ductal lobular units adjacent to invasive breast cancers without the presence of this antigen in cancer tissue was observed. The immunostaining was weak or absent in sigmoid colon carcinomas. In this study we confirm the observation of some authors that NCAM expression occurs in some cases of non-small-cell lung carcinomas.

Malformations of angiogenesis in the low differentiated human carcinomas. immunohistochemical study.

Our previous observations showed that the perivascular mesenchyma of the thin-walled vessels (capillaries) in cancers may be the source of organ-specific stem cells. We suggested that the cells forming vascular channels in altered stroma participate in the tumor development. This study was designed to examine the distribution of the vessels and their appearance in the breast, lung and colon cancers. Using immunohistochemical methods, we have shown that in the low differentiated tumors both CD31 and factor VIII antigens may be expressed in capillaries chiefly on the periphery of neoplastic foci. Many of these vessels were discontinuous, with interruptions or unformed tubules. Sporadically, CD31 protein and factor VIII antigens were not expressed in capillaries inside the very low differentiated cancer cases. It is difficult to assess by immunohistochemical means whether the vascular malformations are the primary or secondary phenomena in the malignancy and why these abnormalities were especially visible in some low differentiated cancers.

Rectal doses in intracavitary brachytherapy of gynecological malignancies: comparison of two dosimetric methods.

PURPOSE: To compare calculated rectal doses obtained by two dosimetric methods in intracavitary brachytherapy of gynecological malignancies. MATERIALS AND METHODS: This analysis included 124 intracavitary applications performed in 102 patients with cervical or endometrial cancer. The pelvic dose distribution based on orthogonal intracavitary placement films was calculated with the computer planning system. In each application the rectal dose was defined in the specific rectal point determined by both the use of a wire marker inserted into the rectum (R1) and by packing the vagina with radio-opaque gauze - the method recommended by the ICRU Report 38 (R2). The comparison included R1 and R2 doses as well as the respective radiobiological equivalent doses determined by the linear-quadratic model (r1 and r2). RESULTS: In 83% of applications the absolute value of R1 was lower than R2. The mean difference between R1 and R2 was 3.7 Gy (95% CI 3.03-4.41 Gy) and between r1 and r2 7.2 Gy (95% CI 5.77-8.56 Gy). These differences were significant (P<0.001 for both comparisons). The difference between the doses was not influenced by the type of applicator and remained significant even when a systemic+/-10% error of method was assumed. CONCLUSION: The rectal point dose determined with the use of rectal wire marker may be underestimated, therefore this method should be discouraged in gynecological brachytherapy.

Sertoli cell tumor in androgen insensitivity syndrome--a case report.

A 26-year-old individual with androgen insensitivity syndrome was operated on for a 3200-g Sertoli cell tumor of the left gonad with retroperitoneal metastases. Six courses of bleomycin, etoposide, and cisplatin chemotherapy followed surgical treatment. Eighteen months after the initial surgery the patient is free of disease and in good health. The association of Sertoli cell tumor with androgen insensitivity syndrome is discussed and the relevant literature is briefly reviewed.

Clodronate in the management of bone metastases: a clinical study of 91 patients.

The aim of our study was to evaluate the efficacy of oral clodronate supplementing systemic therapy and/or palliative irradiation in 91 patients with painful bone metastases. Clodronate was administered at a daily dose of 1600-3200 mg for a median of 11 months (range 3--36 months). Partial or complete pain relief was achieved in 61 of 88 evaluable patients (69%). Response rate to clodronate in patients who additionally received palliative bone radiation was similar to that in patients who did not receive irradiation (68 and 71%, respectively). Eleven out of 12 bed-ridden patients with metastatic bone pain regained the ability of walking after the treatment with clodronate. Bone pain relief lasted from 1.5 to 36 months (mean 9.3 months). Clodronate was well tolerated in all but three cases (3%) in whom the treatment was discontinued due to intensive adverse gastrointestinal effects. In conclusion, we observed satisfactory symptomatic effect and low rate of adverse reactions in patients with metastatic bone lesions treated with oral clodronate. Further large controlled studies with thorough patient monitoring are warranted to evaluate the real benefit of clodronate, and to define its optimal scheduling.

Influence of brachytherapy applicators geometry on dose distribution in cervical cancer.

AIM: Although the relationship between the dose delivered to adjacent organs (urinary bladder and rectum) and the frequency and severity of treatment complications has been reported in many series, the factors influencing pelvic dose distribution are not well defined. The aim of the study was to assess retrospectively the influence of the size of cervical cancer brachytherapy applicators (ovoids and uterine tandems) on pelvic dose distribution and the impact of various therapy-dependent factors on patient anatomy and on dose distribution in particular applications. PATIENTS AND METHOD: The subject of this study were 356 cervical cancer patients treated with Selectron LDR as a part of their radical radiotherapy. Analysed factors included preceding external beam radiotherapy (EBRT) or brachytherapy applications, use of general anaesthesia for application and the system of pellet loading. RESULTS: Significant correlation was found between the size of applicators and doses to bladder, rectum and points B: larger vaginal applicators produced lower dose in bladder and rectum and higher dose in point B (all p < 0.0001), longer uterine tandems produced lower dose in rectum and higher dose in point B (both p < 0.0001). Significant decrease in the frequency of use of large applicators (ovoids: p < 0.0001, tandems: p = 0.055) and worsening of dose distribution, i.e. higher doses to critical organs (respectively: bladder p = 0.0012, rectum p = 0.02) and lower point B dose (p = 0.0001) were observed at consecutive brachytherapy applications. Similar situation occurred in patients, who received EBRT prior to brachytherapy (ovoids: p < 0.001, tandem: p = 0.04, bladder dose: p = 0.009, rectal dose: p = 0.073, point B dose: p = 0.059). Vaginal applicators were larger (p = 0.026) and the dose distribution was better (bladder: p = 0.023, rectum: p = 0.002, point B: p = 0.0001) in patients who had their insertions performed under general anaesthesia. The comparison of 2 consecutively used systems of pellet loading revealed more favourable dose distribution: lower dose for bladder (p = 0.014) and higher dose for point B (p < 0.0001) for the system, which utilised more sources in ovoids and in the distal part of the uterine tandem, in spite of more frequent use of smaller applicators in this group of patients. In multivariate analysis ovoid size was related to preceding external beam radiotherapy (p = 0.025). Uterine tandem length was dependent on the number of preceding intracavitary applications (p < 0.001) and preceding external beam radiotherapy (p = 0.007). Bladder dose was related to preceding brachytherapy (p = 0.011) and the pattern of pellet loading (p = 0.031). Rectal dose was dependent only on the use of general anaesthesia during application (p = 0.001) and point B dose was dependent on the pattern of pellet loading (p < 0.001) and marginally-on the use of preceding external beam radiotherapy (p = 0.06). CONCLUSIONS: The results of this study allow for identification of treatment-related factors determining pelvic dose distribution in cervical cancer brachytherapy and may potentially enable optimisation of this distribution in particular clinical situation.

Skin reactivity to dinitrochlorobenzene in cancer patients.

Delayed skin hypersensitivity to DNCB was evaluated in 179 patients with cancer and in 71 control subjects. Cancer patients had a lower incidence of positive reactions than controls (50.2 vs. 84.5%, p less than 0.001). Incidence of impaired skin reactions in cancer patients varied according to the tumor type. Reactivity was most depressed in patients with lymphatic tumors (23.3% positive results) and least depressed in those with male genitourinary cancer (64.3% positive results). The number of positive results was significantly higher in cancer patients with localized tumor than in those with disseminated disease (60.2% vs. 44.1%, p less than 0.05). DNCB reactivity correlated well with the subsequent course of disease. Incidence of positive results in patients who had remained free of disease after 12 months of follow-up (64.3%) was significantly higher than in patients who had progressive disease (33.3%) or who died of disease (44.8%).