An analysis of the effect of ovoid shields in a selectron-LDR cervical applicator on dose distributions in rectum and bladder.

PURPOSE: A disadvantage of ovoid shields in a Fletcher-type applicator is that these shields cause artifacts on postimplant CT images. CT images, however, make it possible to calculate the dose distribution in the rectum and the bladder. To be able to estimate the possible advantage of having CT information over the use of ovoid shields without having CT information, we investigated the influence of shielding segments in a Fletcher-type Selectron-LDR applicator on the dose distribution in rectum and bladder. METHODS AND MATERIALS: Contours of rectum and bladder were delineated on transaxial CT slices of 15 unshielded applications. Of the volumes contained within these structures dose-volume histograms (DVHs) were calculated. In a similar way, DVHs of simulated shielded applications were calculated. The reduction, due to shielding, of the dose to the 2 cm3 (D2) and 5 cm3 (D5) volume of the cumulative DVHs of rectum and bladder, were determined. An isodose pattern in the sagittal plane through the center of each applicator was plotted to compare the location of the shielded area with the location of maximum dose in rectum and bladder in the unshielded situation. In two cases local dose reductions to the rectal wall were determined by calculating the dose in points at 10-mm intervals on the rectal contours. RESULTS: For the rectum, the reduction of D2 ranged from 0 to 11.1%, with an average of 5.0%; the reduction of D5 ranged from 2.3 to 12.1%, with an average of 6.4%. The reduction of D2 and D5 for the bladder ranged from 0 to 11.9% and from 0 to 11.6%, with average values of 2.2 and 2.6%, respectively. In 8 out of 15 cases the rectal maximum dose was located inferior to the shielded area. In all cases except one the bladder maximum dose was located superior to the shielded area. Local dose reductions on the rectal wall can be as high as 30% or more in an optimally shielded area. CONCLUSIONS: Reductions of D2 and D5 to rectum and bladder due to shielding are rather small, because the shielded area does usually not coincide with the high dose region and even if it does, the shielded area is too small to result in large reductions of these values. Because local dose reductions vary largely, one should proceed with caution when calculating the dose in just one rectal or bladder reference point. Because large overall dose reductions cannot be achieved with shielding, it is safe to use an unshielded applicator when post implant CT images are used to realize optimized dose distributions.

Application of the linear-quadratic-concept for prediction of late complications after combined irradiation of the uterine cervix.

Examining the applicability of the linear-quadratic (LQ) concept for prediction of late rectum and rectosigmoid complications due to combined irradiation of the uterine cervix, it appears that an agreement between clinical experiences and the LQ-based tolerance model can be achieved when relative high tolerance dose values for the separate irradiation techniques are assumed: 70 Gy in 28 fractions for the fractionated irradiation, 70 Gy in 6 days for the continuous irradiation. These tolerance values are derived by assuming a value of 2.5 for the biological parameter a1/a2 (or alpha/beta) as suggested by the LQ-model to be a good approximation for studies of late effects. This investigation shows how fractional tolerance values can be derived for the continuous and fractionated irradiation components. From a simple addition of these values, the total biological effectiveness of a combined irradiation treatment can be determined. This provides a model based on radiobiological parameters for comparison of different treatment schedules, and for dose-adjustments to be made in individual treatments. Especially in cases where the introduction of new afterloading techniques is accompanied by changes in dose rate of the intracavitary irradiation, the LQ-model offers a possibility to prevent mistakes in dosage of critical organs.

Prognostic factors in transitional cell cancer of the bladder: an emerging role for Bcl-2 and p53.

BACKGROUND AND PURPOSE: In a recent study on patients with transitional cell cancer of the bladder treated with curative radiotherapy following TUR-T, we demonstrated that a low apoptotic index and p53 positivity were associated with poor local control. The purpose of this study was to assess the prognostic significance of additional markers implicated in regulation of cell cycle and apoptosis. PATIENTS AND METHODS: Bcl-2, Bax and p21 positivity were detected immunohistochemically on paraffin-embedded pre-treatment biopsies from 83 patients with invasive transitional cell cancer (TCC) of the bladder, treated with radiotherapy. In addition, markers determined in an earlier analysis, i.e.: p53, apoptotic index, cyclin D1, retinoblastoma protein and Ki-67 were included in the multivariate analysis. A stepwise proportional hazard analysis was performed, adjusting for classic prognostic factors (T-stage, grade, multifocality and macroscopic completeness of the TUR). Positivity was defined as >10% of tumor cells staining positive for Bcl-2, Bax and p21, and >20% for p53. RESULTS: Bcl-2 positivity was found in 63%, Bax was positive in 52% and p21 in 55% of cases. In the PH analysis Bcl-2 positivity was found to be related to poor local control (36 vs. 72% at 3 years; P=0.003), as well as to shorter disease-specific survival (74 vs. 94% at 3 years; P=0.017). Evidence for an adverse effect of p53 positivity was also found (local control: 32 vs. 69% at 3 years;P=0.037, disease-specific survival: 76 vs. 92% at 3 years; P=0.043). In an additional PH analysis, we found poor local control rates for bladder cancers with combined Bcl-2 and p53 positivity (17 vs. 65% at 3 years; P=0.0017), and lower disease specific survival (60 vs. 92%; P=0.0024), disease-free survival (7 vs.35%, P=0.0023) and overall survival (39 vs. 80%; P=0.0018). CONCLUSION: This study provides evidence for a poor outcome in patients treated with radiotherapy for TCC of the bladder expressing both Bcl-2 and p53. This relationship was found for local control and disease-free, disease-specific and overall survival.

[Iodine-125 implantation in localized cancer of the prostate; too early for rejoicing]. / Jodium-125-implantatie bij gelokaliseerd prostaatcarcinoom: niet te vroeg juichen.

The role of I-125 implantation in treatment with curative intent of carcinoma of the prostate is not yet perfectly clear. No long-term results in large groups of patients have so far been published. An inherent restriction of the technique is that it is difficult to attain a high dose of radiation in the periphery of the prostate. Consequently, the technique appears to be less or not appropriate for peripherally located tumours or tumours with extracapsular spread. Implantation of I-125 should for the moment be regarded as an experimental therapy. Its application should be limited to strictly selected patients and should be carried out as a part of trials.

[Internal radiotherapy in prostatic carcinoma; disappointing long-term results of retropubic Iodine-125 implantation]. / Inwendige radiotherapie bij prostaatcarcinoom; tegenvallende langetermijnresultaten van retropubische Jodium-125-implantatie.

OBJECTIVE: To evaluate the results of retropubic implantation of 1-125 seeds in patients with carcinoma of the prostate. DESIGN: Retrospective study of records. SETTING: Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands. METHOD: A retrospective study of records provided follow-up data on 75 patients treated in the period 1981-1990 with implantation of 1-125 seeds by a retropubic approach, preceded by pelvic lymph node dissection. Criteria for the treatment were: To, T1 or T2 carcinoma of the prostate, prostatic volume < 40 ml, no contraindications to surgery. RESULTS: The median follow-up was 103 (60-157) months. Four patients died of complications (5%). Major postoperative complications occurred in 23% (17/75) of the cases. Residual carcinoma or distant metastasization was encountered in 43 of the 71 patients (61%). Sixteen patients died from the consequences of the prostatic carcinoma. The 5- and 10-year survival rates amounted to 74% and 42%, respectively, the cancer-specific 5- and 10-year survival rates to 85% and 67%, respectively. At the latest check-up, 18 patients were alive with tumour, 16 of them under hormonal treatment, while 21 patients were alive without indications of active prostatic carcinoma. CONCLUSION: Treatment of carcinoma of the prostate with retropubic implantation of 1-125 seeds resulted in a high incidence of local therapeutic failure and numerous postoperative complications. These results are poorer than those of total prostatectomy and external radiotherapy.

[Good results of bladder-preserving treatment in poorly differentiated and invasive bladder carcinoma using interstitial Iridium-192 radiotherapy]. / Goede resultaten van blaassparende behandeling bij slecht gedifferentieerde en invasieve blaascarcinomen met behulp van interstitiële Iridium-192-radiotherapie.

OBJECTIVE: The analyse the efficacy and safety of conservative treatment for T1G3 and T2-T3a bladder carcinoma. DESIGN: Retrospective. SETTING: National Cancer Institute/Anthoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands. METHODS: Between 1987 and 1994 (7 years) 63 patients with T1G3 or T2-T3a tumours < 5 cm diameter were treated with a combined approach consisting of a transurethral resection, a course of external irradiation (30 Gy in 15 fractions) to the bladder and an Iridium-192 implant procedure. RESULTS: After a mean follow-up of 4.2 years (range 3 months to 7.2 years) 42 patients were alive without tumour. Fourteen patients died from bladder cancer and 4 patients died from intercurrent disease. Three patients were alive with non-curable cancer. Nine patients had an isolated bladder relapse. Seven of these could be salvaged with cystectomy (3 patients) or transurethral resection (4 patients). Eight patients developed distant metastases only and 7 patients distant metastases combined with bladder recurrence. The 5 year actuarial survival was 66%. Acute and late morbidity was limited and mainly related to the surgical procedure. CONCLUSION: Bladder conservation using Iridium-192 implantation is an effective and safe procedure and in selected group of patients with bladder cancer it is a good alternative to radical cystectomy.

[Total prostatectomy--a good option for residual prostate carcinoma after I-125 implantation of external radiotherapy]. / Totale prostatectomie goede mogelijkheid bij residueel prostaatcarcinoom na jodium-125-behandeling of uitwendige radiotherapie.

OBJECTIVE: To evaluate the results of salvage prostatectomy after previous radiation therapy for locally confined prostate cancer. DESIGN: Retrospective. METHOD: Data were collected from the records of all patients with prostate cancer who underwent salvage prostatectomy after I-125 implantation or external radiation therapy in the Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands, 1991-1997. Indications for surgery were: locally confined histologically proven residual cancer, good life expectancy, fit for surgery. Standard preoperative workup was done together with a tumour marker measurement, transrectal ultrasound with biopsy of the prostate and a bonescan. Per- an postoperative complications, pathology result and postoperative PSA were assessed. Progression free survival, overall survival and cancer specific survival were calculated according to the Kaplan-Meier method. RESULTS: 10 patients with a mean age of 67.2 years (range: 57-79) and a median follow up of 78 months (range: 0-89) underwent a total prostatectomy after I-125 implantation (7 patients) or external radiation therapy (3 patients). One patient died after the operation from acute tubular necrosis. One patient developed an internal hernia, requiring surgery. Four patients needed pads during the daytime for stress incontinence for urine. The 5-year progression free survival was 72% (95% confidence interval (95% CI): 44-100), the overall survival was 90% (95% CI: 73-100) and the cancer specific survival was 90% (95% CI: 73-100). No local recurrences were detected. CONCLUSION: The local control and the 5-year survival were good in this selected patient group.

Survival after bladder-preservation with brachytherapy versus radical cystectomy; a single institution experience.

OBJECTIVE: To evaluate the long-term survival following brachytherapy and following cystectomy of patients with invasive bladder cancer treated in our institution. PATIENTS AND METHODS: Between 1988 and 2000 108 patients with solitary, organ confined T1-T2 invasive bladder cancer of < or = 5 cm were treated with a transurethral resection, and a course of external beam radiotherapy (30 Gy) followed by 40 Gy brachytherapy. The overall and disease specific survival rates of these patients are compared with those of 77 patients with T1-T2 invasive bladder cancer treated with cystectomy between 1988-2003. RESULTS: The 5/10 year overall survival rates were 62%/50% after brachytherapy and 67%/58% after cystectomy (p = 0.67). The 5/10 year disease specific survival rates were 73%/67% after brachytherapy and 72%/72% after cystectomy (p = 0.28). When adjusted for age, multiplicity, T-stage, N-stage and grade, the 5/10 year overall survival rates were 65%/53% after brachytherapy and 62%/51% after cystectomy, respectively. The adjusted disease specific survival rates were 75%/70% after brachytherapy and 66%/66% after cystectomy. CONCLUSIONS: This study does not provide evidence regarding survival against the use of bladder preservation with brachytherapy for patients with solitary, T1-T2 invasive bladder cancer of < or = 5 cm diameter, seeking bladder-sparing alternatives to radical cystectomy.

Detection of lymph node invasion in prostatic carcinoma with iliopelvic lymphoscintigraphy.

Eleven patients, ranging in age from 58 to 79 years and referred for 125I implantation because of localised prostatic carcinoma, were subjected to iliopelvic lymphoscintigraphy (IPL) prior to lymph node dissection. Scintigraphy was performed by perianal injection into the ischiorectal fossa of 0.2 ml 99mTc radio-labelled antimony sulphide colloid. The sensitivity of IPL was 100% and the specificity 13%, with a prevalence of positive nodes of 27%. It was concluded that IPL is not useful as a non-surgical method of detecting lymph node invasion in localised prostatic carcinoma because of the low specificity.

Bladder conservation in selected T1G3 and muscle-invasive T2-T3a bladder carcinoma using combination therapy of surgery and iridium-192 implantation.

OBJECTIVE: To retrospectively analyse the efficacy and toxicity of conservative treatment for T1G3 and T2-3a bladder carcinoma and to compare the results with those obtained in a previous study using caesium implantation. PATIENTS AND METHODS: Between 1987 and 1990 12 patients with high-grade T1 tumours and 28 with T2-3a tumours were treated using this combined approach. All tumours were solitary with a diameter not exceeding 5 cm. Treatment consisted of transurethral resection, a course of external irradiation (30 Gy in 15 fractions) to the whole pelvis and an implant procedure. RESULTS: With a mean follow-up of 40 months (range 24-65) 31 patients remained free of disease and nine relapsed: three with distant metastases, two with bladder recurrence and four with combined bladder and distant relapse. Three patients showed tumour at the original site. The 5 years actuarial rate of local control was 84% with an overall 5 years actuarial survival of 86%. Early problems included bladder leakage, wound infection and psychological problems. Late complications in four patients, was transient ulceration at the implant side causing mild dysuria. CONCLUSIONS: Implantation with iridium is equally effective as with caesium but has significantly fewer complications.

Squamous cell carcinoma of the penis. II. Treatment of the primary tumor.

The treatment of the primary tumor in 110 patients with squamous cell carcinoma of the penis seen between 1956 and 1989 was reviewed. Small tumors had generally been treated by penis conserving methods, such as circumcision, local excision and external radiotherapy alone or after circumcision or local excision. Since 1982 we have used the neodymium:YAG laser as a penis conserving method. In 51 patients (46%) penis conserving treatment had been performed and 59 (54%) had undergone some form of amputation. Overall, 16 of 110 patients (15%) had local recurrence. The risk of local recurrence after penis conserving therapy was significantly related to T category, with 10% local recurrences in stage T1 tumors in contrast to 32% and 100% in stages T2 and T3 tumors, respectively. All of the recurrences in patients with stage T1 tumors were strictly local and all were salvaged. In our view penis conserving therapy is a safe procedure in patients with stage T1 tumors and should always be attempted first. Amputation is considered to be overtreatment in these cases. Of 6 recurrences in the conservatively treated stage T2 disease group 4 were strictly local. These were all well or moderately differentiated tumors, not exceeding 3.5 cm. in diameter. We suggest penile conservation for this subgroup of T2 tumors. However, partial amputation is recommended for poorly differentiated stage T2 tumors. Local failure was observed in all stage T3 tumors treated with external radiation. In general, penis conservation in stage T3 tumors should not be attempted with the treatment modalities available to date. Comparing the different methods of penis conservation, used in 49 stages T1 and T2 tumors, no difference in local recurrence rate (18%) was observed among surgery, laser and external beam radiation. In view of the low morbidity, cutting and coagulation properties and minimal tissue changes, use of the neodymium:YAG laser would be our first choice of treatment modality. Penile conservation should be attempted only when frequent and long lasting followup is guaranteed, since local recurrences can appear as late as 8 years after primary treatment.

Squamous cell carcinoma of the penis: accuracy of tumor, nodes and metastasis classification system, and role of lymphangiography, computerized tomography scan and fine needle aspiration cytology.

Among 118 patients with squamous cell carcinoma of the penis treated at our cancer institute between 1956 and 1989, we analyzed the accuracy of classification, using the tumor, nodes and metastasis system. We analyzed the role of lymphography, computerized tomography and fine needle aspiration cytology as additional staging procedures. The primary tumor (T category) was classified incorrectly in 26% of the cases. Overstaging was noted in 10% of the cases because of unsuspected infiltration and overstaging was noted in 16%. Overstaging occurred because of edema and infection masking the actual size and giving a misconception of infiltration, and also because of primary presentation as large exophytic tumors with no or minimal histopathological infiltration. When the regional lymph nodes were categorized simply as positive or negative 80% of the tumors were classified correctly and 20% incorrectly (13% were false positive and 7% were false negative). Regional lymph node invasion that escaped clinical examination was not detected by any imaging examination or fine needle aspiration cytology study. Positive findings were found only in patients with clinically suspected nodes. The classification of regional nodes by clinical examination only is hardly improved by additional imaging studies. Clinical decisions with respect to the management of regional lymph nodes should not be based on negative findings of lymphangiography, computerized tomography or fine needle aspiration cytology. In patients with proved metastasis additional imaging may be of some help in the detection of pelvic node invasion and the determination of the extent of involvement. We recommend lymphangiography as the examination of choice.

Squamous cell carcinoma of the penis. III. Treatment of regional lymph nodes.

We analyzed the management of regional lymph nodes in 110 patients with squamous cell carcinoma of the penis treated at the Netherlands Cancer Institute between 1956 and 1989 with curative intent. Of 66 patients who presented with unsuspected nodes 57 were placed on a surveillance program, while lymph node dissection was performed in 5 (with adjuvant external radiation therapy in 1) and 4 were treated with external radiation therapy only. The management of 40 patients with clinically suspected nodes included surveillance in 5, lymph node dissection in 27 (with adjuvant radiotherapy in 11), biopsy in 4 and external radiation therapy in 4. Postoperative radiotherapy had been given if more than 2 nodes were involved or when extracapsular growth was observed. Overall, 25 patients had a regional recurrence, 5 of whom could be cured subsequently. All regional recurrences developed within 2 years after primary treatment. Analysis showed 100% survival in histologically proved node negative patients (stage pN0). The success of lymph node dissection was related to the extent of the metastatic spread and to the number of involved nodes. Patients with 1 positive node and unilateral inguinal involvement showed a statistically significant survival advantage compared to patients with more extensive spread. Considering the indications for node dissection we found a clear relationship among T category, grade and the probability of lymph node invasion. Patients with stage T1 tumors and stage T2, grades 1 and 2 tumors presented significantly less often with lymphatic invasion than those with other categories of disease and were less likely to have a regional recurrence after treatment of the primary tumor only. In these categories we recommend surveillance of the regional lymph nodes in patients who present with unsuspected nodes. However, patients with stage T2 grade 3, stage T3 and operable stage T4 tumors should undergo an immediate inguinal node dissection because of the high probability of clinically occult lymph node invasion (in our material more than 50%). With respect to the extent of the node dissection, we found that the likelihood of spread to the contralateral and/or pelvic regions was related to the number of invaded nodes in the inguinal region. We recommend contralateral node dissection and unilateral pelvic node dissection when 2 or more positive nodes are found in the dissected groin specimen. Primary pelvic node dissection should be performed in patients who present initially with cytologically or biopsy proved positive inguinal nodes.(ABSTRACT TRUNCATED AT 400 WORDS)