Preoperative Radio Research Articles

Treatment of squamous cell carcinoma of the mobile tongue or tongue margins: An interdisciplinary challenge

Background. Standard treatment is surgery with stage dependent postoperative radio(chemo)therapy, however, for organ preservation preoperative radio(chemo)therapy is used as an individual approach. The present analysis was performed to access outcome and toxicity of radiotherapeutical treatment of squamous cell carcinoma of the tongue. Patients and methods. Sixty-six patients (median age 55 years) with cancer of the mobile tongue (n30) or tongue margins (n36) treated between 1982 and 2006 were retrospectively analyzed. Treatment consisted of definitive- (n13, median dose 66 Gy), adjuvant- (n31, median dose 60 Gy) or neoadjuvant radiotherapy (n22, median dose 40 Gy) and chemotherapy (n34) or immunotherapy (n1). Results. After a median follow-up of 29 months the three- and five-year overall survival (OS) rates were 59% and 46%, respectively. The median OS was 54 months. Forty-two patients achieved complete remission whereas 14 patients showed partial remission. The one- and two-year loco-regional progression-free survival (LRPFS) rates were 76% and 58%, respectively. The median LRPFS time was 36 months. In χ2-test, T-stage showed a trend towards impact on local recurrence (Pearson, p0.082). In multivariate analysis, alcohol consumption (p0.003) and gender (p0.031) were prognostic. Grade III/IV acute toxicity was seen in 52% of patients. None of the locally controlled patients reported grade IV or higher late toxicity. Conclusion. No statistically significant differences between treatment modalities were found, but one should keep in mind that organ preservation plays a major role for quality of life. None of the locally controlled patients reported grade IV or higher late toxicity. However, tumor recurrence is common, especially in advanced tumor stage. Interdisciplinary concepts, further increasing the chance of tumor control are warranted.

Rectal cancer: the impact of lymph node dissection and preoperative radiation in the era of total mesorectal excision

BACKGROUND: The question of adequate lymphadenectomy and application of preoperative radio(chemo)therapy in the era of total mesorectal excision (TME) in rectal cancer has been discussed in recent years without a definitive conclusion. METHODS: Review of the literature. RESULTS: Lymph node metastases (pN) and the lymph node ratio are established prognostic factors in rectal cancer. Therefore, lymphadenectomy has a major impact in rectal cancer surgery. Depending on the tumor location, lymphadenectomy should include the partial or complete removal of the mesorectum in addition to the complete resection of the tumor-bearing rectum segment. The mesorectum includes the regional lymphatic drainage; with the mesorectal fascia it defines the circumferential extent of lymphadenectomy. The aboral lymphadenectomy should reach 5 cm below the macroscopic tumor edge (PME) for tumors of the proximal rectal third, and the complete mesorectum (TME) in the middle and distal third. The oral lymphadenectomy should be performed along the inferior mesenteric artery at least until the branch of the left colic artery. According to the literature, no recommendation exists for routine lateral or extended lymphadenectomy. Official guidelines recommend preoperative radio(chemo)therapy for the treatment of UICC stages II and III rectal cancer in the era of total mesorectal excision. Several studies have shown, however, that preoperative radiation does not improve survival. Side effects were tolerated to prevent a local recurrence in some patients. CONCLUSIONS: Better selection for preoperative radiation is desirable, because in the era of TME and with experienced rectal cancer surgeons the majority of patients do not benefit from radiation therapy.

Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Morphological features and molecular markers in rectal cancer from 95 patients included in the European Organisation for Research and Treatment of Cancer 22921 trial: Prognostic value and effects of preoperative radio (chemo) therapy

In this study, the prognostic and/or predictive value of different proteins (cyclo-oxygenase 2 (COX-2), Ki67 and cleaved cytokeratin (CK) 18) and fibro-inflammatory changes which might be of importance for the response to treatment were evaluated using tissue micro arrays. Samples were obtained from a subset of 95 patients included in the European Organisation for Research and Treatment of Cancer 22921 clinical trial, which randomised patients with rectal cancer to one of four arms treated with preoperative radiotherapy with or without pre- and/or postoperative chemotherapy. From our results, we can conclude that the addition of preoperative chemotherapy to radiotherapy led to significantly less COX-2 upregulation, less proliferation and more inflammation, as was seen in the resection specimen as well as less invasion and metastasis. For COX-2, Ki67 or cleaved CK18, no predictive or prognostic value could be identified. However, the fibro-inflammatory reaction after preoperative radiochemotherapy correlated with T-downstaging and seems to be an important factor for response.

Neoadjuvant and adjuvant therapy in patients with oral squamous cell carcinoma: Long-term survival in a prospective, non-randomized study

Introduction Recently new concepts for the treatment of oral squamous cell carcinomas (SCC) have been developed, which include preoperative simultaneous neoadjuvant radiochemotherapy (RCT) and one stage operation with excision of the tumour and reconstruction. When we consider long-term survival, we find substantial evidence that combined treatment based on neoadjuvant radiochemotherapy is superior to adjuvant treatment including operation and postoperative radiation. Patients and methods We studied two groups consisting of 74 patients given neoadjuvant treatment and 54 treated surgically. Ninety-nine patients suffered from stage III and IV diseases according to the UICC-criteria. Long-term survival was estimated by the Kaplan–Meier method. Results Neoadjuvant treatment increased the prospect of a long-term survival free of tumour. Kaplan–Meier curves estimated a 5-year tumour-free survival in oral squamous cell carcinoma category T1 as 83% in the neoadjuvant group and 70% in the adjuvant group; the corresponding figures for T2 were 79% and 57%, for T3 68% and 33% and for T4 51% and 30%, respectively. The difference for T1, T2 and T4 tumours were significant. The preoperative radio- and chemotherapy were shown to be effective by the fact that pathohistologically resection specimens were free of tumour in 28 patients in the neoadjuvant group. Four patients died during the preoperative combination treatment. Of the patients, 65% in the adjuvant group and 72% in the neoadjuvant group survived the observation period. Conclusion The neoadjuvant treatment results in better 5-year-survival rate than adjuvant treatment.

Local Excision after Radio(chemo)therapy for Rectal Cancer: is it Safe?

According to current opinion, local excision in rectal cancer should be limited to selected T1N0 tumours. Preoperative radio(chemo)therapy provides an opportunity for expanding the use of local excision for more advanced tumours. The key rationale of this approach is the correlation between the radiosensitivity and inherited low aggressiveness of rectal cancer and the correlation between the radiosensitivity of the primary tumour and the radiosensitivity of mesorectal nodal disease. This allows for a selection of local excision for radiosensitive tumours or conversion to abdominal surgery in radioresistant cases. Eleven reports including a total of 311 patients treated with preoperative radio(chemo)therapy and local excision have been published. In some series, the tumours were initially large and unresectable by the transanal approach. Pathological data suggest that local excision must involve all tissue invaded on pre-treatment examination with a margin, even in patients with a clinical complete response. The pooled analysis has shown a local recurrence rate of 1% (1/83) for patients achieving a pathological complete response, 8% (3/40) for ypT1, 11% (4/37) for ypT2 and 3/9 for ypT3. In conclusion, the results of preoperative radio(chemo)therapy and local excision are encouraging and warrant a population-based, multicentre controlled study.

Does rectal cancer shrinkage induced by preoperative radio(chemo)therapy increase the likelihood of anterior resection? A systematic review of randomised trials

Background and purpose According to common conviction rectal tumour shrinkage after preoperative radio(chemo)therapy increases the likelihood of anterior resection (AR). In order to verify this belief, we performed a systematic review of randomised trials. Patients and methods We identified 10 randomised trials encompassing altogether 4596 patients in whom preoperative radio(chemo)therapy resulted in tumour shrinkage in the experimental arm as compared to the control arm. Results Tumour shrinkage observed in the experimental groups did not result in a statistically significant higher ARs rate in any study when we performed an analysis of all the randomised cases. Subgroups of patients considered to be candidates for abdominoperineal resection before randomisation were identified in three trials. A statistically significantly higher rate of ARs was demonstrated in the experimental arm of the CAO/ARO/AIO 94 study. However, in that study, sphincter preservation was a secondary endpoint and some features of the trial may bias the estimation of the effect. The benefit of sphincter preservation was not confirmed by subgroup analyses performed in the Lyon R90-01 study and in the Polish study, which were originally designed to evaluate the sphincter preservation issue. Conclusion The body of evidence gathered from randomised trials does not support the concept of a beneficial effect of preoperative radiotherapy on the ARs rate.

609 POSTER Predictors of disease-free survival after preoperative radio(chemo)therapy and complete resection of T3–4 rectal cancer with or without adjuvant chemotherapy (EORTC 22921)

609 POSTER Predictors of disease-free survival after preoperative radio(chemo)therapy and complete resection of T3–4 rectal cancer with or without adjuvant chemotherapy (EORTC 22921)

Prediction of mesorectal nodal metastases after chemoradiation for rectal cancer: results of a randomised trial. Implication for subsequent local excision

Background and purposeFor patients with rectal cancer treated with full thickness local excision the risk of mesorectal nodal metastases has to be very low. The aim was to assess this risk after preoperative radiotherapy in relation to pathological T-category. Patients and methodsThree hundred sixteen patients with resectable cT3-4 low rectal carcinoma were randomised to receive either preoperative 5×5Gy irradiation with subsequent surgery performed within 7 days or chemoradiation (50.4, 1.8Gy per fraction plus bolus 5-fluorouracil and leucovorin) followed by surgery after 4–6 weeks. The pathological reports of patients who fulfilled entry criteria and had preoperative irradiation followed by transabdominal surgery were analysed. ResultsSignificant downstaging of primary tumour (P<0.001) and of nodal disease (P=0.007) was observed after chemoradiation in comparison with short-course irradiation. In chemoradiation group, for patients with complete pathological response and for ypT1 category, the rate of nodal metastases was low — 5% (95% confidence interval [CI] 0–14%) and 8% (95% CI 0–24%), respectively. The rate of ypN-positive disease in chemoradiation group was similar to that recorded in short-course irradiation group for ypT2 category 26% (95% CI 14–38%) vs. 28% (95% CI 16–40%), P=0.83 and for ypT3-4 category 55% (95% CI 41–69%) vs. 64% (95% CI 54–74%), respectively, P=0.37. For ypT2 category after chemoradiation, the rate of nodal disease remained high even in subgroup with low residual cancer cells density (20%, 95% CI 4–36%). ConclusionsFor patients with tumours downstaged by chemoradiation to ypT0 and ypT1 full thickness local excision may be considered as an acceptable approach, because the risk of mesorectal lymph nodes metastases is low. The selection criteria for preoperative radio(chemo)therapy and local excision are discussed.

Radiotherapy in rectal cancer.

Radiotherapy has an established role in the treatment of rectal cancer. In primary resectable cancer, numerous randomised trials have shown that particularly pre-operative, and to some extent also postoperative, radiotherapy substantially reduces the risk of local failure. This is seen also with total mesorectal excision. Secondary to the reduction in local failures, there is also a slight improvement in survival after pre-operative radiotherapy or postoperative radiochemotherapy. Using appropriate techniques, the morbidity of radiotherapy is low. In non-resectable cancer, radiotherapy may cause down-staging, allow surgery, and may cure some patients. Whether radiochemotherapy is more efficient has yet to be firmly established. The role of pre-operative radio(chemo)therapy to permit more sphincter-preserving procedures with adequate long-term function is not defined.

Emerging standards of radiotherapy combined with radical rectal cancer surgery

For patients with resectable rectal cancer treated with total mesorectal excision, the routine use of radiotherapy should be omitted for stage I of the disease and for lesions located higher than 10 cm from the anal verge. Preoperative radiotherapy may be considered for all patients with a lesion with deep perirectal fat infiltration located in the lower two thirds of the rectum. The other option is to offer postoperative radiotherapy for patients with a positive surgical margin, N+ stage disease, mesorectal tumour implants, high tumour grade, perineural invasion, extramuscular blood and lymphatic vessel invasion and with inadvertent tumour perforation. The lower risk of small bowel damage and probable higher efficacy are arguments for the use of preoperative radiotherapy instead of postoperative radiotherapy. The impairment of anorectal function appears to be most frequent late postirradiation sequel. The analysis of acute complications (including toxic deaths) compliance, cost and convenience favours 5×5 Gy preoperative irradiation with immediate surgery for patients with resectable tumours in comparison to other commonly used schemes of radiotherapy. These advantages should be weighed against approximately 1.5% risk of late neurotoxicity. There is no clear answer to the question whether preoperative conventional radio(chemo)therapy offers an advantage in sphincter preservation. To answer this question, the results of two ongoing randomised trials are awaited. For patients with unresectable cancers, long-term preoperative radio(chemo)therapy with delayed surgery is a preferable scheme. The total mesorectal irradiation should be employed for mid- and low-lying lesions. Therefore, during radiotherapy planning, a contrast enema should be used to identify the anorectal ring, anatomically corresponding with the lowest edge of the mesorectum.

The therapeutic impact of [F18]-2-fluordesoxyglucose PET for the staging and monitoring of oral cancer: a comparative study of PET before and after preoperative radiochemotherapy with CT and histologic data

The lack of sensitivity and specificity of conventional imaging techniques based on morphological criteria is responsible for considerable limitations in the staging and surveillance of oral cancer. Therefore, this study investigated the contribution of [F18]-2-fluordesoxyglucose (FDG) positron emission tomography (PET) to tumour management, with special regard to lymph node involvement and therapeutic monitoring after radiotherapy. In this prospective, observational study, 21 patients with advanced oral cancer, predominantly T3/T4, were evaluated. FDG-PET scans before and after preoperative radio(chemo)therapy were performed and standardized uptake values (SUV) were determined for the tumour site and lymph node areas. PET scans were correlated to histological findings after ablative tumour surgery. FDG-PET yielded superior sensitivity and specificity for tumour and lymph node assessment. The effect of radiotherapy was reflected by the metabolic activity of the tumour, which showed a close correlation with the decrease of FDG uptake and histologic tumour regression. PET detected distant metastases and simultaneous tumours. The authors concluded that FDG-PET is a challenging imaging technique with the potential to improve the staging procedure for oral cancer. In the monitoring of metabolic activity of the tumour in the course of radio(chemo)therapy, FDG-PET allowed objective measurement of the treatment response. H. Schliephake

Endosonographic diagnosis in preoperative radiotherapy of locally advanced rectal carcinoma

Endorectal ultrasound (EUS) is important for the indication of preoperative radio(chemo)therapy of locally advanced rectal carcinomas. Preoperative radio(chemo)therapy causes an increased echogenity of the ultrasound, which histologically corresponds with increased fibrosis. After preoperative radio(chemo)therapy, the accuracy rate of EUS of tumor infiltration depth (T) and lymph-node status (N) is 75% compared with postoperative histology. With the help of EUS before and after radio(chemo)therapy (n = 28 patients) "downstaging" was noticed endosonographically in 10 patients (3 times in T and 7 times in N staging) and "upstaging" in 3 patients (3 times in T and 1 times in N staging). There was no "understaging" of local tumor infiltration depth after preoperative radio(chemo)therapy.

Wilm's tumor in children: review of 38 cases

Analysis of the incidence of the Nephroblastoma and of its clinic, echographic and radiologic aspects. Review of 38 cases handled in the Pediatric Surgery Service of Santa Maria Hospital between January 1960 and January 1987. In addition to the distribution by age and stadiation, the results were studied in 3 groupings corresponding to successive therapeutic phases along this period. The survival is more favourable in the etary group under 3 years old and does not differ substantially in stages I and II. In the analysis of the prognostic to the therapeutic sequences, there was an evident improvement of survival from 0% before 1966 (Surgery and Radiotherapy) to 46.15% in the second phase, 1966-76, with the introduction of Chemotherapy (Actinomycina D). In the last phase after 1977, using the therapeutic scheme of National Wilms Tumour Study (NWTS) survival reached 80.95%. Trying to correlate the prognostic with the histologic type, it turns out to be difficult to make a criterious characterization in the cases submitted to pre-operative Radio and/or Chemotherapy. The advantage of this therapeutic attitude in parallel with the faulaification of the histologic type and the Tumour stadiation is hereby discussed.

Angioma-Like Pseudometamorphosis in Wilms' Tumors Subjected to Preoperative Radio- and Chemotherapy

Six Wilms' tumors (stage III-V), which had undergone preoperative irradiation and chemotherapy, were examined histologically. While mesenchymal and differentiated epithelial tumor elements were preserved to a large extent, blastemic tumor structures were almost completely lacking. Instead, pseudoangioma-like structures similar to cavernous hemangioma prevailed. As demonstrated by transitional pictures, the pseudoangioma-like pattern is a result of the fact that blastemic tumor elements are replaced by blood after therapy-induced necrosis and lysis. The clinical advantages of preoperative treatment are briefly discussed, especially for patients with advanced tumors.