Pilot scale validation campaign of gel dosimetry for pre-treatment quality assurance in stereotactic radiotherapy.

PURPOSE: Complex stereotactic radiotherapy treatment plans require prior verification. A gel dosimetry system was developed and tested to serve as a high-resolution 3D dosimeter for Quality Assurance (QA) purposes. MATERIALS AND METHODS: A modified version of a polyacrylamide polymer gel dosimeter based on chemical response inhibition was employed. Different sample geometries (cuvettes and phantoms) were manufactured for calibration and QA acquisitions. Irradiations were performed with a Varian Trilogy linac, and analyses of irradiated gel dosimeters were performed via MRI with a 1.5 T Philips Achieva at 1 mm3 or 2 mm3 isotropic spatial resolution. To assess reliability of polymer gel data, 54 stereotactic clinical treatment plans were delivered both on dosimetric gel phantoms and on the Delta4 dosimeter. Results from the two devices were evaluated through a global gamma index over a range of acceptance criteria and compared with each other. RESULTS: A quantitative and tunable control of dosimetric gel response sensitivity was achieved through chemical inhibition. An optimized MRI analysis protocol allowed to acquire high resolution phantom dose data in timeframes of ≈ 1 h. Conversion of gel dosimeter data into absorbed dose was achieved through internal calibration. Polymer gel dosimeters (2 mm3 resolution) and Delta4 presented an agreement within 4.8 % and 2.7 % at the 3 %/1 mm and 2 %/2 mm gamma criteria, respectively. CONCLUSIONS: Gel dosimeters appear as promising tools for high resolution 3D QA. Added complexity of the gel dosimetry protocol may be justifiable in case of small target volumes and steep dose gradients.

A multicenter LArge retrospectIve daTabase on the personalization of stereotactic ABlative radiotherapy use in lung metastases from colon-rectal cancer: The LaIT-SABR study.

INTRODUCTION: Stereotactic ablative radiotherapy (SABR) has been shown to increase survival in oligometastatic disease, but local control of colorectal metastases remains poor. We aimed to identify potential predictive factors of SBRT response through a multicenter large retrospective database and to investigate the progression to the polymetastatic disease (PMD). MATERIAL AND METHODS: The study involved 23 centers, and was approved by the Ethical Committee (Prot. Negrar 2019-ZT). 1033 lung metastases were reported. Clinical and biological parameters were evaluated as predictive for freedom from local progression-free survival (FLP). Secondary end-point was the time to the polymetastatic conversion (tPMC). RESULTS: Two-year FLP was 75.4%. Two-year FLP for lesions treated with a BED < 00 Gy, 100-124 Gy, and ≥125 Gy was 76.1%, 70.6%, and 94% (p = 0.000). Two-year FLP for lesion measuring ≤10 mm, 10-20 mm, and >20 mm was 79.7%, 77.1%, and 66.6% (p = 0.027). At the multivariate analysis a BED ≥125 Gy significantly reduced the risk of local progression (HR 0.24, 95%CI 0.11-0.51; p = 0.000). Median tPMC was 26.8 months. Lesions treated with BED ≥125 Gy reported a significantly longer tPMC as compared to lower BED. The median tPMC for patients treated to 1, 2-3 or 4-5 simultaneous oligometastases was 28.5, 25.4, and 9.8 months (p = 0.035). CONCLUSION: The present is the largest series of lung colorectal metastases treated with SABR. The results support the use of SBRT in lung oligometastatic colorectal cancer patients as it might delay the transition to PMD or offer relatively long disease-free period in selected cases. Predictive factors were identified for treatment personalization.

Treating disease progression with osimertinib in EGFR-mutated non-small-cell lung cancer: novel targeted agents and combination strategies.

A precision medicine approach has been successfully applied in medical oncology for the treatment of non-small-cell lung cancer (NSCLC) through the identification of targetable driver molecular aberrations; activating mutations of epidermal growth factor receptor (EGFR) are the most common. Osimertinib, a third-generation, wild-type sparing, irreversible EGFR tyrosine kinase inhibitor (TKI), originally showed a striking activity after progression to first- and second-generation EGFR-TKIs when T790M resistance mutation was identified. Thereafter, upfront use of osimertinib became the standard of care based on overall survival benefit over first-generation TKIs erlotinib and gefitinib as reported in the FLAURA trial. For patients progressing on osimertinib, identification of resistance mechanisms is crucial to develop novel targeted therapeutic approaches. Moreover, innovative drugs or combination therapies are being developed for cases in which a specific resistance mechanism is not identifiable. In this review, the post-osimertinib treatment options for EGFR-mutated NSCLC are analyzed, with an outlook to ongoing clinical trials. An algorithm to guide clinicians in managing progression on osimertinib is proposed.

Modelling late stool frequency and rectal pain after radical radiotherapy in prostate cancer patients: Results from a large pooled population.

AIM: To investigate late gastrointestinal toxicity in a large pooled population of prostate cancer patients treated with radical radiotherapy. Normal tissue complication probability models were developed for late stool frequency and late rectal pain. METHODS AND MATERIALS: Population included 1336 patients, 3-year minimum follow-up, treated with 66-80Gy. Toxicity was scored with LENT-SOMA-scale. Two toxicity endpoints were considered: grade ⩾2 rectal pain and mean grade (average score during follow-up) in stool frequency >1. DVHs of anorectum were reduced to equivalent uniform dose (EUD). The best-value of the volume parameter n was determined through numerical optimization. Association between EUD/clinical factors and the endpoints was investigated by logistic analyses. Likelihood, Brier-score and calibration were used to evaluate models. External calibration was also carried out. RESULTS: 4% of patients (45/1122) reported mean stool frequency grade >1; grade ⩾2 rectal pain was present in the TROG 03.04 RADAR population only (21/677, 3.1%): for this endpoint, the analysis was limited to this population. Analysis of DVHs highlighted the importance of mid-range doses (30-50Gy) for both endpoints. EUDs calculated with n=1 (OR=1.04) and n=0.35 (OR=1.06) were the most suitable dosimetric descriptors for stool frequency and rectal pain respectively. The final models included EUD and cardiovascular diseases (OR=1.78) for stool frequency and EUD and presence of acute gastrointestinal toxicity (OR=4.2) for rectal pain. CONCLUSION: Best predictors of stool frequency and rectal pain are consistent with findings previously reported for late faecal incontinence, indicating an important role in optimization of mid-range dose region to minimize these symptoms highly impacting the quality-of-life of long surviving patients.

Bladder spatial-dose descriptors correlate with acute urinary toxicity after radiation therapy for prostate cancer.

PURPOSE: To assess bladder spatial-dose parameters predicting acute urinary toxicity after radiotherapy for prostate cancer (PCa) through a pixel-wise method for analysis of bladder dose-surface maps (DSMs). MATERIALS & METHODS: The final cohort of a multi-institutional study, consisting of 539 patients with PCa treated with conventionally (CONV:1.8-2Gy/fr) or moderately hypo-fractionated radiotherapy (HYPO:2.2-2.7Gy/fr) was considered. Urinary toxicity was evaluated through the International Prostate Symptoms Score (IPSS) administered before and after radiotherapy. IPSS increases ⩾10 and 15 points at the end of radiotherapy (ΔIPSS⩾10 and ΔIPSS⩾15) were chosen as endpoints. Average DSMs (corrected into 2Gy-equivalent doses) of patients with/without toxicity were compared through a pixel-wise method. This allowed the extraction of selected spatial descriptors discriminating between patients with/without toxicity. Previously logistic models based on dose-surface histograms (DSH) were considered and replaced with DSM descriptors. Discrimination power, calibration and log-likelihood were considered to evaluate the impact of the inclusion of spatial descriptors. RESULTS: Data of 375/539 patients were available. ΔIPSS⩾10 was recorded in 76/375 (20%) patients, while 30/375 (8%) experienced ΔIPSS⩾15. The posterior dose at 12mm from the bladder base (roughly corresponding to the trigone region) resulted significantly associated to toxicity in the whole/HYPO populations. The cranial extension of the 75Gy isodose along the bladder central axis was the best DSM-based predictor in CONV patients. Multi-variable models including DSM descriptors showed better discrimination (AUC=0.66-0.77) when compared to DSH-based models (AUC=0.58-0.71) and higher log-likelihoods. CONCLUSION: DSMs are correlated with the risk of acute GU toxicity. The incorporation of spatial descriptors improves discrimination and log-likelihood of multi-variable models including dosimetric and clinical parameters.

Lymph-node relapsed prostate cancer management and PET-driven external beam radiotherapy: salvage or palliative treatment?

New imaging modalities such as choline- positron emission tomography (PET) or PET/computed tomography (CT) may be useful to identify prostate cancer patients with small volume, limited nodal relapse ("oligo-recurrent"), potentially amenable to metastasis directed treatment (e.g. radiotherapy,) with the aim of long-term control of the disease, even in a setting traditionally considered prognostically unfavorable, so usually gone to palliative treatment. This report reviews the diagnostic tools and the main published data about the role of PET or PET/CT driven radiation therapy, (not only for the diagnosis, but also for the planning) in relapsed node prostate carcinoma, as an alternative therapeutic strategy than surgery or androgen deprivation therapy.

Treatment of seriously compromised teeth: decision- making criteria and treatment options.

The aim of this article was to describe the case of a patient who presented to our attention with severe periodontal disease, complicated by furcation involvement on elements 16 and 17. In addition, the radiographic exam revealed the presence of a deep intrabony defect distal to tooth 15. Surgical therapy is performed after the resolution of the endodontic component of the intra-bony defect on the element 15 and consists on osteoplasty and ostectomy on 16, guided tissue regeneration (GTR) on 15, extraction of 17 and bi-laminar connective tissue graft for the coverage of the recession on tooth 13. The patient is visited monthly and 9 months after surgery, the definitive metal-ceramic crown is delivered and adapted to tooth 16. At 18 months, the patient's periodontal situation is re-evaluated and the pocket depth results healthy (probing depth of tooth 15=2 mm). The surgical practices reported in this work allowed for functional and esthetic rehabilitation of periodontally compromised teeth. The RSR and the GTR represent conservative surgery that allow the preservation of compromised dental elements and if properly performed, guarantee excellent survival rates of the elements in the arch. For these reasons, when it is possible, the RSR and the GTR are a valid alternative to implantology and are to be considered as the first therapeutic option in the treatment plan.

Behavior of endosseous one-piece yttrium stabilized zirconia dental implants placed in posterior areas.

AIM: Considering that zirconia dental implants are indicated for the rehabilitation of highly esthetic areas, the aim of this work was to investigate the functional behavior of these implants positioned in the posterior regions of the jaws. METHODS: The study included 6 patients with 14 zirconia implants positioned in posterior (molar) areas of the jaws. Immediately after surgery, all implants were restored with temporary crowns or bridges. Clinical radiographic evaluation was performed 6 months after surgery and subsequently every year. At these follow-up visits, periodontal indexes were recorded and peri-apical radiographs were taken in order to calculate marginal bone loss. RESULTS: The success and survival rates were 100%. The modified bleeding index (mBI) and modified plaque index (mPLI) were respectively equal to 0.57±0.51 and 0.29 ± 0.47 at 4-year follow-up. The overall mean probing depth of the implants was 3.13±0.87 mm. The mean marginal bone loss was +0.665 mm 4 years after surgery. CONCLUSION: Considering the limits of our study, as regards to the data concerning peri-implant tissue health, marginal bone loss and survival and success rates of zirconium implants placed in posterior areas, we can conclude that the data reported are very encouraging although the number of implants observed is still limited.

Combined treatment of odontogenic keratocysts: initial marsupialization and successive enucleation with peripheral ostectomy plus Carnoy's solution application. A five-year follow-up experience.

AIM: The odontogenic keratocyst (KCOT) is a locally aggressive, cystic jaw lesion with a high growth potential and a propensity for recurrence. Considering its neoplastic features, treatments of keratocysts are required and they are generally classified as conservative or aggressive. However, although in literature there are several studies, the choice of treatment strategies remains controversial. We report a two-stage protocol based on initial marsupialization and successive enucleation. METHODS: Three cases of large KCOTs have been treated by initial marsupialization and, after a mean period of six months, successive enucleation with peripheral ostectomy and application of Carnoy's solution was performed. RESULTS: All patients were instructed in daily irrigation using chlorhexidine 0.2% during the period of marsupialization. After enucleation, good healing was obtained in all cases and from two up to five years of follow-up, there is no evidence of recurrence. CONCLUSION: Two-stage surgical treatment protocol of keratocyst leads to complete healing, preservation of important anatomical structures and absence of recurrence.

Late rectal bleeding after 3D-CRT for prostate cancer: development of a neural-network-based predictive model.

The aim of this study was to develop a model exploiting artificial neural networks (ANNs) to correlate dosimetric and clinical variables with late rectal bleeding in prostate cancer patients undergoing radical radiotherapy and to compare the ANN results with those of a standard logistic regression (LR) analysis. 718 men included in the AIROPROS 0102 trial were analyzed. This multicenter protocol was characterized by the prospective evaluation of rectal toxicity, with a minimum follow-up of 36 months. Radiotherapy doses were between 70 and 80 Gy. Information was recorded for comorbidity, previous abdominal surgery, use of drugs and hormonal therapy. For each patient, a rectal dose-volume histogram (DVH) of the whole treatment was recorded and the equivalent uniform dose (EUD) evaluated as an effective descriptor of the whole DVH. Late rectal bleeding of grade ≥ 2 was considered to define positive events in this study (52 of 718 patients). The overall population was split into training and verification sets, both of which were involved in model instruction, and a test set, used to evaluate the predictive power of the model with independent data. Fourfold cross-validation was also used to provide realistic results for the full dataset. The LR was performed on the same data. Five variables were selected to predict late rectal bleeding: EUD, abdominal surgery, presence of hemorrhoids, use of anticoagulants and androgen deprivation. Following a receiver operating characteristic analysis of the independent test set, the areas under the curves (AUCs) were 0.704 and 0.655 for ANN and LR, respectively. When evaluated with cross-validation, the AUC was 0.714 for ANN and 0.636 for LR, which differed at a significance level of p = 0.03. When a practical discrimination threshold was selected, ANN could classify data with sensitivity and specificity both equal to 68.0%, whereas these values were 61.5% for LR. These data provide reasonable evidence that results obtained with ANNs are superior to those achieved with LR when predicting late radiotherapy-related rectal bleeding. The future introduction of patient-related personal characteristics, such as gene expression profiles, might improve the predictive power of statistical classifiers. More refined morphological aspects of the dose distribution, such as dose surface mapping, might also enhance the overall performance of ANN-based predictive models.

Use of endosseous one-piece yttrium-stabilized zirconia dental implants in premolar region: a two-year clinical preliminary report.

AIM: The aim of this work was to clinically and radiographically evaluate survival and success rate of zirconia dental implants positioned in premolar area during a follow-up period of at least 12 months up to 24 months. METHODS: Sixteen patients were treated with 26 zirconia implants. All implants received immediate temporary restorations and 6 months after surgery were definitively restored. Twelve to 14 months after implant insertion, a clinical-radiographical evaluation was performed in order to estimate peri-implant tissues health and peri-implant marginal bone loss. RESULTS: The survival rate was 96.16%. The success rate was 91.6%. CONCLUSION: Because of the limited number of implants, conclusions may not be considered significant even if results are encouraging. Further scientific information regarding clinical use of zirconia dental implants are needed, as well as prospective long-term clinical studies in order to understand if zirconia implants may represent a valid alternative to titanium implants.

Fitting late rectal bleeding data using different NTCP models: results from an Italian multi-centric study (AIROPROS0101).

BACKGROUND AND PURPOSE: Recent investigations demonstrated a significant correlation between rectal dose-volume patterns and late rectal toxicity. The reduction of the DVH to a value expressing the probability of complication would be suitable. To fit different normal tissue complication probability (NTCP) models to clinical outcome on late rectal bleeding after external beam radiotherapy (RT) for prostate cancer. PATIENTS AND METHODS: Rectal dose-volume histograms of the rectum (DVH) and clinical records of 547 prostate cancer patients (pts) pooled from five institutions previously collected and analyzed were considered. All patients were treated in supine position with 3 or 4-field techniques: 123 patients received an ICRU dose between 64 and 70 Gy, 255 patients between 70 and 74 Gy and 169 patients between 74 and 79.2 Gy; 457/547 patients were treated with conformal RT and 203/547 underwent radical prostatectomy before RT. Minimum follow-up was 18 months. Patients were considered as bleeders if showing grade 2/3 late bleeding (slightly modified RTOG/EORTC scoring system) within 18 months after the end of RT. Four NTCP models were considered: (a) the Lyman model with DVH reduced to the equivalent uniform dose (LEUD, coincident with the classical Lyman-Kutcher-Burman, LKB, model), (b) logistic with DVH reduced to EUD (LOGEUD), (c) Poisson coupled to EUD reduction scheme and (d) relative seriality (RS). The parameters for the different models were fit to the patient data using a maximum likelihood analysis. The 68% confidence intervals (CI) of each parameter were also derived. RESULTS: Forty six out of five hundred and forty seven patients experienced grade 2/3 late bleeding: 38/46 developed rectal bleeding within 18 months and were then considered as bleeders The risk of rectal bleeding can be well calculated with a 'smooth' function of EUD (with a seriality parameter n equal to 0.23 (CI 0.05), best fit result). Using LEUD the relationship between EUD and NTCP can be described with a TD50 of 81.9 Gy (CI 1.8 Gy) and a steepness parameter m of 0.19 (CI 0.01); when using LOGEUD, TD50 is 82.2 Gy and k is 7.85. Best fit parameters for RS are s=0.49, gamma=1.69, TD50=83.1 Gy. Qualitative as well as quantitative comparisons (chi-squared statistics, P=0.005) show that the models fit the observed complication rates very well. The results found in the overall population were substantially confirmed in the subgroup of radically treated patients (LEUD: n=0.24 m=0.14 TD50=75.8 Gy). If considering just the grade 3 bleeders (n=9) the best fit is found in correspondence of a n-value around 0.06, suggesting that for severe bleeding the rectum is more serial. CONCLUSIONS: Different NTCP models fit quite accurately the considered clinical data. The results are consistent with a rectum 'less serial' than previously reported investigations when considering grade 2 bleeding while a more serial behaviour was found for severe bleeding. EUD may be considered as a robust and simple parameter correlated with the risk of late rectal bleeding.

Minimal requirements in prostate cancer irradiation: a consensus document by the AIRO Lombardia Cooperative Group.

PURPOSE: With the aim of establishing clinical and technical criteria to homogenize radiotherapy practice, a working group of AIRO-Lombardia (Associazione Italiana di Radioterapia Oncologica--Gruppo regionale della Lombardia) has tried to define minimal requirements for radical and postoperative irradiation in prostate cancer. The document has been structured in such a way as to be also of interest to the urological and medical oncology communities. METHODS: The working group, composed of representatives of most of the regional radiotherapy departments in the Lombardy region, had monthly meetings during 1996 and 1997. The document on minimal requirements has been derived from the participants' combined experience and knowledge, from review of the literature, and from a 1995 regional survey on current practice of prostate irradiation. RESULTS: Minimal requirements for radical and postoperative irradiation of prostate cancer have been defined with respect to treatment strategies, pre-treatment diagnostic evaluation and staging, treatment prescription, preparation and execution, and quality assurance procedures. CONCLUSION: Standards of reference for minimal requirements in prostate cancer irradiation adapted to the regional structures and resources have been defined.

Combined modality treatment for esophageal cancer.

This paper describes the mechanisms of action of ionizing radiations combined with antineoplastic drugs. Some relevant drugs for the combined modality treatments of locally advanced lung cancer are reported. The meta-analyses including randomized trials comparing single agent (radiotherapy or chemotherapy) versus combined chemotherapy and radiotherapy in patients with unresectable non small cell lung cancer and limited small cell lung cancer are then reviewed. The clinical outcome in relation to different schedules of chemoradiotherapy (sequential, alternating and concurrent) is also focussed.

The role of radiotherapy in the treatment of carcinoma of the prostate: a survey of clinical practices in Lombardy, Italy, by the AIRO-Lombardia Cooperative Group. Italian Association for Radiation Oncology.

AIMS AND BACKGROUND: We report the results of a survey performed in 1994 by the AIRO-Lombardia Cooperative Group, on the clinical patterns of radiation treatment for prostatic carcinoma in Lombardy, Italy, involving all radiotherapy centers serving an overall local population of about 8,800,000 people. METHODS: A questionnaire was sent to all 13 radiotherapy centers throughout Lombardy, asking for demographic and treatment details concerning the local population of patients with a localized (T1-4, N0-1, M0) carcinoma of the prostate treated with radiotherapy; 12 centers responded, making the basis for the present report. RESULTS: Analysis of collected data showed that in Lombardy: a) approximately 400 patients per year are irradiated for a localized carcinoma of the prostate, accounting for less than 30% of the total expected number of patients with this disease presentation; b) a complete staging (with PSA, transrectal ultrasonography, abdomino-pelvic CT or MRI scan and total-body bone scan) is performed in over 95% of patients before initiating radiotherapy; c) significant differences exist between radiotherapy centers as regards treatment planning and delivery. CONCLUSIONS: An urgent need exists for implementing procedures aimed at standardizing radiotherapy procedures within Lombardy.

Role of postoperative radiation therapy in the management of early stage primary gastric non-Hodgkin's lymphomas: a retrospective analysis.

BACKGROUND: Clinical approaches to early primary gastric non-Hodgkin's lymphomas have not yet been clearly defined, and the role of postoperative radiotherapy remains a matter of discussion. METHODS: Twenty-seven patients with early primary gastric non-Hodgkin's lymphoma were observed from December 1978 to December 1990 at our Institution. They were staged according to Musshoff and Schmidt-Volmer (19) as I E (n = 16), II E 1 (n = 7) and II E 2 (n = 4). All of them underwent local combined treatment, consisting of surgery and postoperative radiotherapy; chemotherapy was also administered to 10 patients, mainly with the CHOP regimen, for 4-6 cycles before radiotherapy. Irradiation was delivered using 10 MV photons from a linear accelerator. Large abdominal fields were employed in 21 cases with daily fractions of 1.5-2 Gy up to a median total dose of 30 Gy (range: 27-36 Gy). Six patients were irradiated only on the surgical bed up to 40.5 Gy (range: 39-40.5 Gy). RESULTS: The 5-year overall and disease-free survivals were respectively 92.4% and 89.8%. The main known prognostic indicators, stage of disease, type of surgery as well as age and sex, were not found to be statistically significant in our series. No clear difference emerged between patients sequentially treated with the combination surgery-chemotherapy-radiotherapy and those who did not receive adjuvant chemotherapy. Two patients recurred at distant sites, but no local failure was seen during the follow-up. CONCLUSIONS: Although no firm conclusion can be drawn, our experience, in agreement with recent published reports, points out that the use of postoperative radiotherapy is associated not only to favorable results in terms of local control and survival, but also, and moreover, to a negligible incidence of side effects and sequelae. However, in the absence of multi-institutional prospective randomized studies, whose activation is nowadays strongly warranted, the exact role of adjuvant therapies remains a matter of discussion, and the optimal treatment of early primary gastric non-Hodgkin's lymphoma still depends on individual experience and the physician's philosophy.

The role of radiotherapy in the treatment of stage III non-small cell lung cancer: a survey of clinical practices in Lombardy, Italy, by the Airo*-Lombardia Cooperative Group.

AIMS AND BACKGROUND: The role of radiotherapy in the treatment of stage III non-small cell lung cancer is controversial. The aim of this survey was to investigate the use of this modality in current clinical practice in Lombardy, a highly industrialized region of northern Italy. METHODS: A questionnaire was sent to all 13 radiotherapy centers in Lombardy, covering statistical, clinical, technical and strategical aspects, and the responses were analyzed. RESULTS: A wide range of attitudes was observed among participating radiation oncologists; the percentage of cases treated with curative intent varied largely between centers (4-100%), as did the proportion of patients given to radiation only rather than combined modality treatment (5-100% vs 0-90%). CONCLUSIONS: An urgent need exists for better cooperation between all clinicians involved in lung cancer treatment, pursuing the goals of a more uniform clinical practice and a more aggressive clinical research attitude.

Postoperative radiation therapy for adult soft tissue sarcomas: a retrospective study.

From 1977 to 1988, 81 adult patients with localized soft tissue sarcomas at different sites received postoperative external beam radiotherapy (55 Gy median dose) following primary conservative surgery. Sixty were new referrals after primary surgery and 21 were irradiated after excision of recurrent disease. With a median follow-up of 4 years (range: 2-13) the 5-year overall survival (Kaplan-Meier) and local control were 55.5% and 56% respectively, while 5-year disease-free survival is 49%. There were 26 (32%) local relapses and 22 (27%) distant failures. Local recurrence was the sole pattern of failure in 16 patients (20%). Functional and cosmetic results were good to excellent in most cases. In our series local control is the main prognostic variable influencing survival (P less than 0.0001), and its probability seems to show a link with the type of surgical procedure, with a trend (P less than 0.13) in favor of wide total excision. Postoperative radiation therapy represents an acceptable treatment strategy for ASTS, but further improvements are expected from future controlled clinical trials, aiming at the achievement of the definitive cure of these tumors.

[Exclusive radiotherapy of carcinoma of the hypopharynx. Retrospective study of a series of 100 patients]. / La radioterapia esclusiva del carcinoma dell'ipofaringe. Analisi retrospettiva di una casistica di 100 pazienti.

From January 1980 to December 1987, 100 patients with carcinoma of the hypopharynx, staged according to TNM (UICC-1978) criteria, received exclusive radiation therapy at the Radiotherapy Department of the General Hospital of Varese. The median follow-up is 9 months (range: 1-97). Irradiation was delivered with 60Co or with 10 MV photons and tissue-equivalent bolus. Two opposed parallel lateral fields or rotational technique were used, with progressive shrinking of treated volume in order to spare the spinal cord after 45 Gy. Direct fields of electron beams (6-15 MeV) were employed as boosts on the residual nodes. Median total doses: 64.5 Gy to T and N1-3, 45 Gy to N0. A conventional fractionation (2 Gy once a day, 5 times a week) was used in 37 outpatients, while an accelerated hyperfractionated regimen (1.5 Gy twice a day, 5 times a week, with a six hours' interval between each fraction) was employed in 63 inpatients, in order to shorten hospitalization. The five-year overall survival (Kaplan-Meier) of the 100 treated patients is 10%, while the five-year disease-free survival of the 40 patients in complete clinical remission at the end of radiation therapy is 19.8%. The five-year loco-regional control rate after exclusive radiotherapy is 19.1%. Complete remission at the end of treatment seems to represent the only significant prognostic variable affecting survival: five-year overall survival is 32% for the 40 patients achieving complete remission and only 4.4% for the others (p less than 0.05). On the contrary, tumor extension (T class) seems to affect only the two-year local control rate: 35.2% and 10.9% for T1 + T2 and T3 + T4 respectively (p less than 0.1). The main cause of failure after radiation therapy is represented by the lack of control at the primary site (T) alone or associated with regional adenopathies (N). The analysis of isoeffect parameters, according to CRE model, has not shown any evident dose-response relationship for local control. Late effects were observed in 7% of the patients and were similar to those reported in the literature. The occurrence of both distant metastases, 3% in our experience, and secondary tumors (9%) is lower than those previously reported. The present retrospective study strongly reconfirms the inadequacy of exclusive radiation therapy as the sole treatment modality for carcinoma of the hypopharynx and suggests the need of combination therapy (surgery and radiation) as primary treatment.(ABSTRACT TRUNCATED AT 400 WORDS)