Hans H. Lien

Postchemotherapy Retroperitoneal Surgery Remains Necessary in Patients With Nonseminomatous Testicular Cancer and Minimal Residual Tumor Masses

PURPOSEnTo determine preoperative parameters that predict the histology of specimens obtained by retroperitoneal lymph node dissection (RPLND) in patients with nonseminomatous germ cell cancer (NSGCT) whose residual mass was </= 20 mm in diameter after modern cisplatin-based induction chemotherapy.nnnPATIENTS AND METHODSnEighty-seven patients with metastatic NSGCT underwent RPLND after having received cisplatin- or carboplatin-based induction chemotherapy. In all patients, the largest diameter of the residual mass on the transaxial plane was </= 20 mm, as assessed by abdominal computed tomography (CT) immediately before RPLND.nnnRESULTSnComplete fibrosis or necrosis was found in 58 patients (67%), teratoma was found in 23 patients (26%), and vital malignant germ cell tumor was found in six patients (7%), including one patient with rhabdomyosarcoma in the RPLND specimen. In five of the six latter patients, the residual lesion was </= 10 mm at pre-RPLND CT. No pre- or postchemotherapy clinical or radiologic parameter was identified that significantly predicted the histology of the residual mass.nnnCONCLUSIONnOne third of retroperitoneal postchemotherapy lesions </= 20 mm contained residual vital tumor tissue, despite modern chemotherapy regimens. Therefore, postchemotherapy RPLND remains necessary in patients with minimal-size residual lesions to facilitate easy and safe follow-up and initiate additional therapy as early as possible, thus avoiding recurrences.

Radiological and clinical assessment of long-term brain tumour survivors after radiotherapy

BACKGROUND AND PURPOSEnLate adverse effects of therapeutic brain radiotherapy (RT) may develop after long latency periods and our objective was to assess long-term brain tumour survivors following RT to large partial brain volumes.nnnMATERIALS AND METHODSnAssessment of MRI, SOMA/LENT score, quality of life and neuroendocrine function was performed in 33 adult brain tumour patients 6-25 years following RT. Fraction dose was 1.8 Gy to a median total dose of 54 Gy (range: 45.0-59.4 Gy). Ten patients had been given two opposing portals including one whole hemisphere, while 23 patients had in addition received an ipsilateral field. In 25 patients the hypothalamic and pituitary area had been included in the RT field. Results were compared within the study group and towards the general population matched for age and gender.nnnRESULTSnAll patients had white matter changes with increased signal intensity on T2 and FLAIR images. Discrete lesions (grade 1), beginning confluence of lesions (grade 2), and large confluent areas (grade 3) were present in 8, 8 and 17 patients, respectively. Patients treated with intra-arterial chemotherapy and patients at higher age at follow-up had significantly more grade 3 changes. Atrophy, lacunar lesions and contrast enhancement was found in 17, 18 and 23 patients, respectively. Significantly worse clinical status and quality of life was found in patients with white matter changes grade 3 or atrophy. Patients given full-dose RT to less volume did not have significantly less toxicity. Two cases of meningioma were found at 16 and 22 years after RT. Nineteen neuroendocrine abnormalities were observed in 16/25 patients.nnnCONCLUSIONSnExternal radiotherapy to the brain at a standard fractionation regime will cause varying degrees of late neurotoxicity and/or neuroendocrine disturbances in most patients. Life-long follow-up is recommended.

Histology of tumor residuals following chemotherapy in patients with advanced nonseminomatous testicular cancer

A total of 111 patients with advanced nonseminomatous testicular cancer underwent cisplatin-based combination chemotherapy, followed by surgical removal of residual masses in 101. Surgery included retroperitoneal lymph node dissection in 92 patients, thoracotomy in 19 and hepatic resection in 1 (11 patients underwent 2 operations). Complete necrosis and/or fibrosis was found in 52 operative specimens, mature teratoma in 37 and vital malignant tumor in 12. Of the 11 patients who underwent 2 operations 4 had complete necrosis and/or fibrosis in both histological specimens. After a median observation of 55 months 83 of 89 patients with complete necrosis and/or fibrosis or mature teratoma were without evidence of disease. Only 7 of 12 patients with vital malignant tumor in the operative specimen survived without evidence of disease. Relapses were observed in 16 patients, 4 of them in the retroperitoneal space. Of the 16 relapses 5 were in 12 patients with residual vital malignant tumor, 5 in 37 patients with post-chemotherapy mature teratoma and 4 in 52 patients with complete necrosis and/or fibrosis after chemotherapy. Two patients with recurrence did not undergo an operation. In patients in whom post-chemotherapy retroperitoneal lymph node dissection is considered complete necrosis and/or fibrosis can be predicted by the combination of several factors, including absence of teratomatous elements in the testicular tumor, complete response on post-chemotherapy computerized tomography, and normal alpha-fetoprotein and human chorionic gonadotropin levels after chemotherapy (sensitivity 83%, specificity 76% and correctly predicted 79%). With the knowledge of these factors it seems possible to omit post-chemotherapy retroperitoneal lymph node dissection in approximately 20% of the patients with advanced metastatic nonseminomatous testicular cancer with initial retroperitoneal tumors.

Post-chemotherapy lymph node histology in radiologically normal patients with metastatic nonseminomatous testicular cancer

A total of 37 patients with initially advanced metastatic nonseminomatous testicular cancer underwent retroperitoneal lymph node dissection after cisplatin-based combination chemotherapy. Abdominal computerized tomography was negative at retroperitoneal lymphadenectomy (lymph nodes not exceeding 10 mm. in the transverse computerized tomography plane). Complete necrosis and fibrosis were found in 25 patients. In 11 patients the retroperitoneal lymphadenectomy specimen showed a mature teratoma. Residual vital malignant tumor was observed in 1 patient. Neither the initial size of the retroperitoneal mass nor the histological status of the primary tumor was predictive of the histological findings in the retroperitoneal lymphadenectomy specimen. The high frequency of mature teratoma raises the question whether omitting post-chemotherapy surgery is a safe routine policy in patients with negative computerized tomography, especially if long-term followup is not feasible. We recommend a post-chemotherapy retroperitoneal operation as routine treatment even in patients with negative computerized tomography.

Late recurrence of testicular cancer.

The aim of this study is to draw attention to important points concerning the clinical management of late relapses in testicular cancer. From 1972 to 1982 The Norwegian Radium Hospital (NRH) has treated 1,008 patients with testicular cancer. Fifteen (1.5%) of these patients relapsed 36 months or more after their primary treatment. The patients medical records were reviewed in this retrospective study, and all available histological sections were reevaluated. Six patients had pure seminoma initially and relapsed after an average of 54.5 months. Five of them had subjective symptoms due to recurrent tumor. Four patients relapsing in the supradiaphragmatic lymph nodes only are alive with no evidence of disease after an observation time of 17 to 30 months after treatment. Nine nonseminoma patients relapsed after an average of 85 months (36 to 194 months). Eight of these were aware of subjective signs or symptoms due to recurrent tumor leading to the diagnosis of the relapse. Four of these patients are alive with no evidence of disease after an observation time of 4 to 46 months after treatment. Two of these patients relapsed with pure mature teratoma. Late relapses do occur although they are rare events. Seminoma patients relapsing in the lymph nodes only have a good prognosis, and nonseminoma patients have a slightly poorer prognosis. Active follow-up for relapse detection is not justified. All testicular cancer patients should instead be informed of typical signs and symptoms that can be related to a relapse and encouraged to seek medical help for further investigation.

Assessment of tumor oxygenation in human cervical carcinoma by use of dynamic Gd-DTPA-enhanced MR imaging

Increased knowledge of the physiological basis behind the signal enhancement in tumors during dynamic contrast‐enhanced magnetic resonance (MR) imaging may be useful in development of predictive assays based on this technique. In the present work, the relative signal intensity (RSI) increase in gadopentetate dimeglumine (Gd‐DTPA)‐enhanced MR images of patients with cervical carcinoma was related to tumor perfusion, vascular density, cell density, and oxygen tension (pO2). The patients were subjected to MR imaging before the start of treatment (N = 12) and after two weeks of radiotherapy (N = 8). Perfusion was determined from the kinetics of contrast agent in tumors and arteries, vascular density and cell density were determined from tumor biopsies, and pO2 was determined by polarographic needle electrodes. The maximal RSI was correlated to perfusion (P = 0.002) and cell density (P = 0.004), but was not related to vascular density. There was also a correlation between pO2 and perfusion (P < 0.001). Moreover, pO2 tended to be correlated to cell density (P = 0.1), but was not related to vascular density. There was a significant correlation between RSI and pO2, regardless of whether the median pO2 (P < 0.001) or the fraction of pO2 readings below 2.5 mmHg (P < 0.001), 5 mmHg (P < 0.0001), or 10 mmHg (P < 0.001) was considered. Our results suggest that the Gd‐DTPA‐induced signal enhancement in MR images of cervical tumors is influenced by both perfusion and cell density. These parameters are also of major importance for tumor oxygenation, leading to a correlation between signal enhancement and oxygenation. Dynamic contrast‐enhanced MR imaging may therefore possibly be useful in prediction of treatment outcome. J. Magn. Reson. Imaging 2001;14:750–756.

Recombinant interferon alfa-2a with or without vinblastine in metastatic renal cell carcinoma

Twenty patients with measurable metastatic renal cell carcinoma (RCC) were treated with interferon alfa‐2a (Roferon®‐A)36 × 106 U intramuscularly 3 times weeklyalone (2 patients) or in combination with vinblastine, 0.10–0.15 mg/kg intravenously every 2 to 3 weeks. Objective responses in the lungboneliverand lymph node metastases were seen in 6 of 18 evaluable patients. Dose reduction of interferon alfa‐2a was necessary in 19 of the 20 patients due to intolerable flu‐like side effects and fatigue. Bone marrow suppression and increase of γ‐GT represented the most often observed objective toxicity. The preliminary results of this combination treatment in RCC are promising and warrant randomized studies exploring the role of vinblastine. The dose of interferon alfa‐2a should be reduced by 50% to avoid excessive toxicity and to maximizepatient compliance.

A randomized study evaluating radiotherapy versus chemotheraphy in patients with inoperable non-small cell lung cancer

A combination of cisplatin (70 mg/m2 i.v. day one) and etoposide (100 mg/m2 i.v. day one, 200 mg/m2 orally days 2 and 3) repeated every third week to a maximum of 4 cycles were compared with high voltage radiotherapy, 42 Gy given in 15 fractions over a 3-week period to patients with inoperable non-small cell lung cancer (a shield was used in the posterior field to reduce the total spinal dose less than 40 Gy). One hundred and eighteen patients received radiotherapy; the median survival was 10.6 months compared to 10.5 months for the 116 chemotherapy patients (p = 0.81). The objective response rate (CR + PR) was 42% for the radiotherapy and 21% for the chemotherapy group (p = 0.009). At progression it was optional to cross over to the other treatment modality or to receive phase II chemotherapy. Thirty patients primarily treated with radiotherapy and 54 allocated to chemotherapy received second line antineoplastic treatment.

Clinical stage I carcinoma of the cervix. Value of MR imaging in determining invasion into the parametrium.

Using MR imaging with a body coil parametrial invasion was determined prospectively in 169 consecutive patients considered on the basis of clinical examination to have carcinoma confined to the cervix. After radical hysterectomy correlation with histologic examination was performed for the left and right parametrium separately. The criterion for parametrial invasion was a high-signal-intensity lesion with disruption of the full thickness of the cervical stroma combined with areas of abnormal signal intensity within the parametrial region on T2-weighted images. Histologic examination showed that 18 parametria in 13 patients were invaded by tumor. MR had an overall accuracy of 93%, a sensitivity of 89%, and a specificity of 93% in demonstrating parametrial involvement. Positive and negative predictive values were 43% and 99%. The main weakness of MR was 21 false-positive tests. This represents a limitation when MR is performed with a body coil.

Computed tomography/magnetic resonance based volume changes of the primary tumour in patients with prostate cancer with or without androgen deprivation

BACKGROUND AND PURPOSEnTo evaluate changes of the volume of the cancerous prostatic gland during androgen deprivation (AD) started immediately after diagnosis (IAD). Hypothetically, these data would assist the radiotherapist to determine the appropriate duration of pre-radiotherapy downsizing neoadjuvant luteinizing hormone releasing hormone (LHRH) treatment. A second aim was to assess any increase of the prostatic volume during the 1st year of diagnosis in patients who were allocated to a deferred treatment policy (DAD). METHODS AND MATERIALS Thirteen patients in the IAD cohort and 13 patients in the DAD group, all with T1-3pN1-2M0 prostate cancer, had regular computed tomography/magnetic resonance (CT/MR) examinations during the 1st year after randomization within the EORTC-GU trial 30846. Pre-treatment prostate specific antigen (PSA) values were available in only 12 patients.nnnRESULTSnIn the IAD group the prostate gland decreased with significant difference as compared with the DAD patients (P=0.033). As compared with the pre-treatment situation the prostate gland in the IAD group was reduced in size by 18, 35, and 46% at 1, 6, and 12 months, respectively. In four of six evaluable IAD patients the prostatic volume continued to shrink after achievement of the nadir PSA level (at 3 months). In three of the 13 DAD patients the prostate volume increased by >25% during the 1st 3 months after randomization.nnnCONCLUSIONnIf neoadjuvant androgen deprivation is applied before local treatment to downsize the volume of the cancerous prostate gland, our limited data suggest that such treatment should last at least 6 months in order to achieve a maximal effect in the majority of patients. In about 1/4 of untreated patients an increase in the prostate volume by >25% may occur within 3 months of diagnosis. If no AD is given, radiotherapy should start within this period.