Analysis of efficacy and safety of vismodegib therapy in patients with advanced basal cell carcinoma - real world multicenter cohort study.

BACKGROUND: Basal cell carcinoma (BCC) is the most frequent non-melanoma skin cancer. The basis of treatment is surgical resection. The treatment of locally advanced and metastatic disease is currently based on sonidegb or vismodegib, small molecule inhibitors of the hedgehog signalling pathway. OBJECTIVES: The study aimed to retrospectively analyse the efficacy and safety of treatment with vismodegib in 108 patients with locally advanced or metastatic disease treated from August 1st, 2017 to December 31st, 2020. The primary objective was to evaluate the objective response rate (ORR), overall survival (OS) and progression-free survival rates. The secondary aims of the study were the disease control rate, the incidence of adverse events (AEs) and the estimation of the factors that potentially impact the treatment outcome and patient survival. METHODS: Patients treated in national drug programme were enrolled into this retrospective cohort study. Evaluation of the treatment efficacy was performed according to CT/MRI scans and by the response evaluation criteria in solid tumours (RECIST) 1.1. The safety evaluation was performed according to the Common Terminology Criteria for Adverse Events v. 5.0 (CTCAE) classification and severity assessment. RESULTS: The median duration of treatment was 14 months (range 1-94 months). The median progression-free survival reached 30.5 months (95% CI; 24.8-36.3), and the progression-free survival rate after 6, 12 and 24-months were 92%, 78% and 61%, respectively. The median overall survival was 41.5 months (95% CI; 31.6-51.3), and the overall survival rate after 1, 2 and 3 years accordingly 86%, 73% and 60%. The univariant and multivariant analysis indicated that the female gender is an independent positive prognostic factor of progression-free survival. CONCLUSIONS: The response to treatment is the prognostic factor for response maintenance and better overall survival. The therapy was well tolerated with the safety profile consistent in general with known from previous studies.

NMR-based metabolomics in real-time monitoring of treatment induced toxicity and cachexia in head and neck cancer: a method for early detection of high risk patients.

INTRODUCTION: Nutritional treatment in head and neck squamous cell carcinoma cancer (HNSCC) patients undergoing radio-/chemo-radiotherapy (RT/CHRT) is complex and requires a multidisciplinary approach. In this study the real-time dynamic changes in serum metabolome during RT/CHRT in HNSCC patients were monitored using NMR-based metabolomics. OBJECTIVES: The main goal was to find the metabolic markers that could help prevent of acute radiation sequelae (ARS) escalation. METHODS: 170 HNSCC patients were treated radically with RT/CHRT. Blood samples were collected weekly, starting from the day before the treatment and stopping within the week after the RT/CHRT completion, resulting in a total number of 1328 samples. 1H NMR spectra were acquired on Bruker 400 MHz spectrometer at 310 K and analyzed using principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). Additional statistical analyses were performed on the quantified metabolites. RESULTS: PCA has detected a group of distinct outliers corresponding to ketone bodies (3HB, Ace, AceAce). These outliers were found to identify the individuals at high risk of weight loss, mainly by the 3HB changes, which was confirmed by the patients' medical data. In the OPLS-DA models a transition from the lowest to the highest weight loss is seen, defining the metabolic time trajectories for the patients from the studied groups during RT/CHRT. 3HB is a relatively sensitive marker that allows earlier identification of the patients at higher risk of > 10% weight loss. CONCLUSION: Our findings indicate that metabolic alterations, characteristic for malnutrition or cachexia, can be detected already at the beginning of the treatment, making it possible to monitor the patients with a higher risk of weight loss.

High-dose radiotherapy alone for patients with T4-stage laryngeal cancer.

BACKGROUND AND PURPOSE: The purpose of this retrospective study was to report on the efficacy of radiotherapy alone in patients with T4-stage laryngeal cancer and to establish the prognostic value of (a) the size and location of the extralaryngeal tumor extensions and (b) of emergency tracheostomy. PATIENTS AND METHODS: A group of 114 patients were treated with definitive radiotherapy between 1990 and 1996. The piriform recess was involved in 37 cases (33 %), the base of the tongue and glosso-epiglottic vallecula in 34 cases (30 %), and the hypopharyngeal wall in 10 cases (9 %). In 16 cases (14 %), emergency tracheostomy was performed before radiotherapy. The mean total dose was 68 Gy (range, 60-77.6 Gy). The mean treatment time was 49 days (range, 42-74 days). RESULTS: Actuarial 3-year local control (LC) was noted in 42 % of patients, disease-free survival (DFS) in 35 %, and overall survival (OS) in 40 %. The best prognosis was for the lesion suspected of cartilage infiltration: 56 % 3-year LC. The worst results were noted in the cases with massive infiltrations spreading from the larynx through the hypopharynx: 13 % 3-year LC. Emergency tracheostomy before radiotherapy was significantly connected with the worst treatment results (p = 0.000): 3-year LC in patients with tracheostomy was 0 % vs. 48 % in patients without tracheostomy. CONCLUSION: Conventional radiotherapy of T4 laryngeal cancer is a method of treatment with limited effectiveness. The efficacy of radiotherapy is dependent on the location and extent of extralaryngeal infiltrations. Emergency tracheostomy is a prognostic factor connected with the worst prognosis.

Acute mucosal reactions in patients with head and neck cancer. Three patterns of mucositis observed during radiotherapy.

PURPOSE: To investigate the individual pattern of acute mucosal radiation reactions (AMRR) in patients with head and neck cancer who were treated with radiotherapy alone. Reactions were evaluated daily on an individual basis according to the Dische scoring system. MATERIALS AND METHODS: Treatment of 87 head and neck cancer patients comprised either conventional fractionation- (CF; n = 33), accelerated fractionation (AF; n = 33), hyperfractionated- (HPEFX; n = 12) or hypofractionated (HPOFX; n = 9) radiotherapy with radical intent. Daily evaluation of AMRR progression was performed prospectively using a modified, morphologically functional Dische scoring system. The daily sums of the score parameters were subsequently used to construct an individual AMRR course curve for each patient. RESULTS: A latency period ranging from 3 to 14 days between the start of radiotherapy and the occurrence of the first AMRR symptom was observed in all patients. Based on the three different shapes of AMRR course curve observed during radiotherapy, three types of AMRR course can be described: (1) a continual increase in AMRR intensity until the completion of radiotherapy; (2) the incidence of a plateau phase following the increase in AMRR (increase-plateau course) and (3) decreasing AMRR intensity with a healing phase. A continual increase in AMRR intensity was observed in about 25 % of CF and AF patients and in more than 50 % of HPOFX treatments. This type of reaction was not observed in the HPEFX group. The increase-plateau course was noted in the majority of AF and CF patients; in almost half of those treated with HPOFX and in all HPEFX patients. A decreasing AMRR intensity course was observed in 23 % of all patients, although not observed at all in the HPEFX and HPOFX fractionation groups. CONCLUSION: The course of AMRR during radiotherapy can differ between individual patients. After the initial increase in AMRR intensity, a stabilization of the reaction--visible as a plateau phase on the course curve--is observed in the majority of patients. A proportion of the irradiated patients experience a continual increase in AMRR intensity up until the end of radiotherapy. A further group of patients exists in whom signs of AMRR healing are observed during the final stages of radiotherapy.

Ewing's sarcoma of the larynx. Effective treatment with organ preservation.

Extraskeletal Ewing's sarcoma arising in the head and neck region is an extremely rare malignant neoplasm. We describe the unusual case of a tumor originating in the larynx of a 68-year-old male with hoarseness and occasional aphonia. We report successful treatment with sequential chemo- and radiotherapy. Complete regression and larynx preservation with voice function recovery was achieved. To our knowledge, this is the first report of this type of tumor in the larynx with cartilage invasion that documents the effectiveness of radiotherapy as an alternative to surgical management. At present, after 30 months of follow-up, the patient is free of tumor relapse and in very good condition.

Prognostic role of tumor volume for radiotherapy outcome in patient with T2 laryngeal cancer.

BACKGROUND AND PURPOSE: Tumor volume (TV) is recognized as a prognostic factor of treatment outcome for head and neck tumors but is not routinely included in the treatment decision-making process. The purpose of the study was to define its prognostic role for patients with T2 laryngeal cancer. MATERIAL AND METHODS: TV of 160 patients who underwent RT between 2002 and 2006 for T2 laryngeal squamous cell carcinoma were reviewed. The tumor was located in the glottis and epiglottis in 82 (51%) and 78 (49%) patients, respectively. TV was manually contoured on pretreatment, planning, contrast-enhanced CT scans and the volumetric measurement (cm3) was calculated by the volume algorithm. RESULTS: The median TV value was 2.01 cm3 (range 0.15-21.68 cm3). The median TV was significantly lower in patients with glottic tumors (p<0.0001), N0 (p<0.001), or well histopatologically differentiated tumors (p=0.01). A significant correlation between TV, hemoglobin concentration (p<0.01), and total dose (TD; p<0.001) was observed. On univariate analyses, TV influenced local control (LC; p=0.02) and overall survival (OS, p<0.001). On multivariate analysis, both age (HR 1.038, p=0.03) and TV (HR=1.075, p=0.01) remained significantly related to LC and OS (age: HR 1.038, p=0.005; TV: HR 1.097, p=0.0001). CONCLUSION: Large TV worsen prognosis of patients with T2 laryngeal cancer. A large TV is more common for supraglottic, poorly differentiated tumors and may suggest higher risk of nodal spread. The routine estimation of TV prior to therapy may be essential in order to select the best treatment option for patients with T2 laryngeal cancer.

Acute mucosal radiation reactions in patients with head and neck cancer. Patterns of mucosal healing on the basis of daily examinations.

PURPOSE: The goal of this research was to evaluate the healing processes of acute mucosal radiation reactions (AMRR) in patients with head and neck cancer. MATERIALS AND METHODS: In 46 patients with oral and oropharyngeal cancer patients irradiated with conventional (n = 25) and accelerated (n = 21) dose fractionation AMRR was evaluated daily during and after radiotherapy. Complex of morphological and functional symptoms according to the Dische score were collected daily until complete healing. RESULTS: Duration of healing after the end of radiotherapy ranged widely (12-70 days). It was on the average 8 days longer for accelerated than for conventional radiotherapy (p = 0.016). Duration of dysphagia was also longer for accelerated irradiation (11 days, p = 0.027). Three types of morphological symptoms were observed as the last symptom at the end of AMRR healing: spotted and confluent mucositis, erythema, and edema. Only a slight correlation between healing duration and area of irradiation fields (r = 0.23) was noted. In patients with confluent mucositis, two morphological forms of mucosal healing were observed, i.e., marginal and spotted. The spotted form was noted in 71% of patients undergoing conventional radiotherapy and in 38% of patients undergoing accelerated radiotherapy. The symptoms of mucosal healing were observed in 40% patients during radiotherapy. CONCLUSION: The wide range of AMRR healing reflects individual potential of mucosa recovery with longer duration for accelerated radiotherapy. Two morphological forms of confluent mucositis healing were present: marginal and spotted. Healing of AMRR during radiotherapy can be observed in a significant proportion of patients.

Predictors of radiotherapy outcome in patients with T2 supraglottic carcinoma.

The decision regarding treatment of early supraglottic carcinoma remains controversial. Single institution clinical data of patients with T2 supraglottic carcinoma treated exclusively with radiotherapy in terms of prognostic factors and treatment results were analyzed. Patient-related factors that would potentially by useful for optimal therapeutic decision to be undertaken were especially investigated. Between 1994 and 2004, 78 patients with T2 supraglottic carcinoma underwent radiotherapy (RT) in Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Gliwice Branch, Poland. There were 54 (69%) males and 24 (31%) females in the median age of 61 years. There were 17 (22%) patients with N+. Median body mass of patients before (BM0) and after RT (BM1) was 74 kg (range 45.2-130 kg) and 72.9 kg (range 49.9-122.5 kg), respectively. Median hemoglobin concentrations before (Hb0) and after (Hb1) RT were 14.3 and 13.4 g/dl, respectively. Median change of Hb concentration during RT (dHb) was -0.8 g/dl. All were treated up to total doses (TD) ranged from 62.5 to 72 Gy. The overall treatment time (OTT) ranged from 30 to 70 days. Estimates of local control (LC), ultimate local control (uLC), and overall survival (OS) were calculated using the Kaplan-Meier method. Log rank statistics, Cox proportional hazard model and step-wise Cox regression hazard model were employed to identify prognostic factors for LC, uLC, and OS in univariate and multivariate analyses. The 5-year LC, RC, uLC and OS rates were 85, 92, 88, and 56%, respectively. In multivariate analysis N+ (p = 0.01) and prolonged OTT (p = 0.03) significantly decreased LC. Females (p = 0.02), higher BM0 (p = 0.03), and HB0 (p = 0.006) significantly prolonged OS. Patient-related factors like gender, hemoglobin concentration, and body mass may predict treatment outcome. Radiotherapy is effective for T2 supraglottic carcinoma of the larynx unless higher dose intensity is provided. Involved regional lymph nodes significantly deteriorate locoregional cure.

Prognostic value of hemoglobin concentration in radiotherapy for cancer of supraglottic larynx.

PURPOSE: The aim of this work is the estimation of correlations between hemoglobin concentration either before or after radiotherapy and local tumor control probability for laryngeal cancer. METHODS AND MATERIALS: Retrospective analysis of 847 cases of laryngeal supraglottic squamous cell carcinoma treated with radiation alone was performed using maximum likelihood estimations, and step-wise logistic regression. All patients were in good initial performance status (Karnofsky index >70). The minimum follow-up time was 3 years. RESULTS: Logistic regression showed that the hemoglobin concentration after radiotherapy is an important prognostic factor. There was a very strong correlation between hemoglobin concentration and tumor local control probability. Hemoglobin concentration at the beginning of radiotherapy does not correlate with treatment outcome, but any decrease of hemoglobin during therapy is a strong prognostic factor for treatment failure. CONCLUSIONS: Although regression models with many variables may be instable, the present results suggest that hemoglobin concentration after treatment is at least as important as overall treatment time. It was not possible to find out whether the low concentration of hemoglobin is an independent cause of low TCP or whether it reflects other mechanisms that may influence both hemoglobin level and the TCP.

Clinical radiobiology of glottic T1 squamous cell carcinoma.

PURPOSE: Radiation therapy is the treatment of choice for early glottic squamous cell cancer in many institutions over the world. Despite a relatively homogenous clinical model of T1 glottic tumors for the fractionation studies, the relationships between dose-time parameters remain unclear. To analyze the influence of fractionation parameters and hemoglobin level on tumor cure, this study has been performed. MATERIALS AND METHODS: This is a retrospective review of 235 patients with T1N0M0 glottic cancer treated by radiation therapy alone given in a conventional schedule with 5 fractions each week. The individual total dose, dose per fraction, and overall treatment time (OTT) ranged from 51-70 Gy, 1.5-3.0 Gy, and 24-79 days, respectively. The median follow-up was 48 months. Patient data--total dose, dose per fraction, OTT, and hemoglobin level (Hb) measured before the radiation treatment--were fitted by the mixed LQ/log-logistic model. RESULTS: The 5-year local relapse-free survival rate was 84%. All parameters included in the mixed LQ/log-logistic model improved the fit significantly. The dose-response curve for 235 patients with T1 glottic cancer was well defined and steep, and showed significant decrease in tumor control probability (TCP) when total doses were below 61 Gy. The 10-day prolongation of OTT, from 45 to 55 days, decreased the TCP by 13%. The dose of 0.35 Gy/day, compensated repopulation during the 1 day of prolongation, which indicates a potential doubling time (Tpot) for glottic T1 tumor clonogens of 5.5 days. The drop of Hb level of 1 g/dl (from 13.8 g/dl to 12.8 g/dl) gave a 6% decrease of TCP, provided that OTT was 45 days. CONCLUSION: The significant correlation between the total dose, overall treatment time, hemoglobin concentration, and tumor control probability has been found for T1 glottic cancer.

Planned and unplanned gaps in radiotherapy: the importance of gap position and gap duration.

Local tumour control in 971 patients with squamous carcinoma of the supraglottic larynx has been examined in relation to the occurrence of gaps in radiation therapy. The minimum follow-up time was 3 years. The reasons for a gap in radiotherapy fell into four categories: independent of the patient (national holidays, machine break-down, etc.), planned gaps (split-course therapy), severe normal-tissue reactions, and intercurrent disease. Only 11.7% of patients had no gap at all, 75.5% a single gap, and 2.1% had more than four gaps. The probability of tumour control increased with dose in all patient sub-groups; the average percentage increase for a 1% increase in dose was 4.3. The data were subjected to multivariate analysis, leading to the following conclusions. Patients in whom there was a single gap showed a remarkable trend of local control: if the gap began before day 19 after the start of therapy, the local tumour control was considerably below that in patients who did not suffer a gap in treatment. The local tumour control in patients whose gap began at day 20-29 was indistinguishable from that in patients who had no gap in treatment. A gap further towards the end of treatment was again associated with a severe drop in local control. This trend was independent of the recorded cause of the gap. The mechanism of this phenomenon is not clear. The effect of the timing of a treatment gap appears in this data set to have had a considerable impact on outcome and our observations should stimulate further study of this phenomenon in other clinical settings.

Cell-cycle progression during continuous low dose rate irradiation of a human bladder carcinoma cell line.

At very low radiation dose rates, the proliferation of mammalian cells continues unaffected but as the dose rate is increased there comes a point at which it is interrupted. The dose rate at which this happens is often thought to be a significant factor in the effects of brachytherapy: it may determine the range from an implanted source at which cell-cycle redistribution and repopulation effects will occur. By means of mitotic counts and DNA flow cytometry, we have examined the dose rate effect in a human bladder carcinoma cell line (MGH-U1). Irradiation at dose rate 0.1 cGy/min had little or no effect on cell-cycle progression. Suppression of mitosis and arrest of cells in G2 was observed at 0.4 cGy/min and above. Surprisingly, the duration of mitotic arrest showed little dose rate dependence; it was followed by an overshoot of cells in mitosis after 24-39 h of irradiation. An even more pronounced overshoot of cells in G2 occurred and persisted throughout the irradiation period. The cell kinetic data indicate that after the temporary block in cell-cycle progression, cell proliferation continued at all dose rates up to 1.4 cGy/min. We have evaluated these results in the light of previous studies in this department of the dose rate effect for cell survival in the MGH-U1 cell line. After 24 h irradiation at 1.4 cGy/min the surviving fraction was below 10(-2), also after 30 h at 1.0 cGy/min. When cell-cycle blockade is considerable, so is the level of cell killing. Flow-cytometric data therefore are dominated by the properties of cells that are doomed to die.(ABSTRACT TRUNCATED AT 250 WORDS)

Randomized clinical trial on 7-day-continuous accelerated irradiation (CAIR) of head and neck cancer - report on 3-year tumour control and normal tissue toxicity.

PURPOSE: To evaluate tumour and normal tissues 3-year response to 7-day-a-week continuous accelerated irradiation (CAIR) compared to a conventional treatment (5 days per week) in a randomized trial. MATERIALS AND METHODS: One hundred patients with squamous cell carcinoma of the head and neck in stage T(2-4)N(0-1)M(0) were entered into the trial between December 1, 1993 and June 30, 1996. Dose per fraction of 2.0 Gy (to the end of 1994), and 1.8 Gy (since January 1, 1995) was the same in both arms and delivered once a day at regular 24-h intervals to total dose in the range of 66-72 Gy (depending on tumour stage). The only difference was overall treatment time being 5 weeks in the CAIR and 7 weeks in control arm. RESULTS: Actuarial 3-year local tumour control was 82% in the CAIR and 37% in the control group (P<0.0001) with reduction in local recurrence rate of 83%. Actuarial 3-year overall survival was 78 and 32% (P<0.0001), respectively. Confluent mucositis was significantly more severe and lasted longer in the CAIR than in control arm. After 2.0 Gy fractions five of 23 patients (22%) in the CAIR developed early necroses over a period of 2-4 months of follow-up which can be considered as a consequential to severe protracted acute mucosal reactions (CLE). For this reason dose per fraction was lowered to 1. 8 Gy and the CLE was not observed again until now. Thus the overall rate of CLE decreased to 10%. CONCLUSIONS: The gain in tumour control is likely the effect of shortening of overall treatment time by 14 days and regular continuous dose delivery during the whole course of radiation therapy including weekends. A 7-day schedule produces more severe acute mucosal reactions lasting longer than in conventional fractionation, however tolerable by patients. Relatively high rate (22%) of CLE in the 7-day arm observed during the first year of the study was eliminated by decreasing dose per fraction from 2.0 Gy to 1.8 Gy.

Acute mucositis in the stimulated oral mucosa of patients during radiotherapy for head and neck cancer.

In 16 patients treated for squamous cell carcinoma of the oral cavity or oropharynx with an accelerated split course regimen, acute mucosal reactions were significantly less in the left buccal mucosa which had been repeatedly painted with 2% silver-nitrate solution for several days before radiotherapy than in the unpainted right buccal mucosa.

Randomized clinical trial on accelerated 7 days per week fractionation in radiotherapy for head and neck cancer. Preliminary report on acute toxicity.

PURPOSE: Toxicity of an accelerated 7 days per week fractionation schedule (arm A) was evaluated and compared with a conventional 5 days per week treatment (arm B) in a randomized trial. MATERIALS AND METHODS: Forty-four patients with squamous cell carcinoma of the head and neck in stage T2-4Nzero-1Mzero were included in the study. Total dose and dose per fraction of 2.0 Gy given once-a-day at 24 h intervals were the same in both arms of the trial. The only difference was the overall treatment time being 5 weeks in arm A and 7 weeks in arm B. RESULTS: Analysis of severe mucosal reactions shows significant difference between arm A and B, with regard to both maximum score and duration of severe mucositis. Confluent mucositis (score > 15 according to the Dische system) lasting longer than 3 weeks developed in 48% of patients in arm A and only in 5% in arm B. In group A seven (30%) late effects (osteo- and soft tissue necrosis) occurred during 7-12 month follow-up with two reactions (10%) in group B being suspected as late effects. There was significant association between acute reactions and late effects in arm A, suggesting that the late effects are consequential. CONCLUSION: The high incidence of severe acute reactions and consequential late effects suggests that the accelerated treatment in arm A (using daily fractions of 2.0 Gy, 7 days per week) gives unacceptable toxicity.

The impact of delivered dose errors on local control of irradiated advanced laryngeal cancer.

On the basis of 1,015 entrance and 863 exit dose in vivo measurements, 863 calculations of midline dose were done, and the average deviation and ranges of its value were estimated. Data of 710 advanced larynx cancers were reviewed in order to achieve dose-response relationship. Patients data were fitted directly to L-Q model using maximum likelihood estimation. In 16.5% of measurements the deviation of midline dose was larger than -5.2%. A steep dose response relationship for TCP was found. Considering -5.2% deviation of 2 Gy fraction and 72 Gy of total dose, the 17% (from 48 to 31%) decrease of TCP was found. It shows that deviations of delivered dose influence the tumor control probability and that after systematic error finding during fractionated radiotherapy the value of remaining fraction size and total dose should be modified to compensate the change of TCP.

Radiobiological predictors of tumor and acute normal tissue response in radiotherapy for head and neck cancers.

Importance of two assay of the measurements of potential doubling time (Tpot.) and survival fraction at 2.0 Gy (SF2) and a method modifying acute radiation response of normal oral mucosa are discussed. Tumor clonogen repopulation accelerates around day 28 of treatment and the rate of repopulation is not constant but continuously increases from about 0.3 Gy/day to 1.0-1.3 Gy/day between day 28 and 65 of treatment. It may suggest that Tpot. values decrease respectively. The relevance of the Tpot. measurements prior to the treatment to clinical situations is discussed. The SF2 value reflects the intrinsic radiosensitivity of human tumors. The SF2 values are expected to be valuable as a predictors for tumor response to radiation. Variations in the SF2 values depending on tumor characteristics and assay methods are discussed in relation to the dose-response and tumor cure probability. The effect of modification of an accelerate repopulation in the oral mucosa by stimulation with 2% silver nitrate solution is presented. Although the presented prognosticators are different in their nature, they might provide a rational basis for selecting patients into optimal radiation treatment and might allow to modify radiation response of dose-limiting normal tissues.

Comparative estimation of cure rates for supraglottic and glottic cancer in radiotherapy.

There are some clinical evidences, that the same types of tumors originated from neighboring anatomical structures can significantly differ in their response to radiation therapy. Squamous cell cancer of supraglottis and glottis could be good examples of this phenomenon. The purpose of the study was to compare the radiocurability of cancers localized in the upper and medium level of the larynx. From 1985 to the end of 1989, 544 patients with squamous cell cancer of the larynx were treated by radiotherapy alone. There were 388 patients with supraglottic cancer and 156 patients with glottic cancer. The total dose was in the range of 59-74 Gy. The end-point criteria were overall (OS) and disease-free survival (DFS). Generally, 5-year overall and disease-free survival rates were significantly more favorable for glottic cancer patients than for supraglottic cancer (67 and 63% vs. 40 and 36%, respectively). Significant differences in both disease-free and overall survival between supraglottic and glottic cancer in aspect of several analyzed clinical prognostic factors were found for: male sex, age, pattern of tumor growth, clinical performance status, radiation total dose lower than 70 Gy, fraction doses and overall treatment time. In all these prognostic categories 5-year survival rates were lower for supraglottic cancer patients. This tendency disappeared when the treatment results were compared in aspect of tumor stage (T). Tumor cure doses for 50% probability of local control (TCD50) in supraglottic cancer were estimated as: 61 Gy (T(1+2)) and 66 Gy (T3). In glottic cancer the lower TCD50 values of 54.5 Gy (T(1+2)) and 61 Gy (T3) were found in comparable treatment time. The comparative estimation of cure rates (i.e. OS and DFS) of laryngeal cancer treated by radiation alone showed that in aspect of almost all analyzed prognostic factors the greater risk of treatment failure was significantly associated with supraglottic origin.

Hyperfractionated radiotherapy for Burkitt-type lymphoma. Radiobiological aspects.

A case of Burkitt-type lymphoma treated by accelerated hyperfractionated irradiation combined with the COP chemotherapy is presented. The effectiveness of treatment was evaluated on the basis of the growth curve and the radiobiological aspects are discussed. During the treatment, the initial volume doubling time (Td) of 15 days was shortened to 4.5 days suggesting accelerated tumor growth. From dose response curve estimated for clinical data taken from literature, an effDo of 1.37 Gy was calculated. Surviving fraction after 58 Gy given in the twice-a-day regimen (b. i. d.) was 10(-19) suggesting local tumor control. However, only partial remission was observed. This nonradical effect may likely result in accelerated repopulation of surviving tumor clonogenic cells. This suggests that such a fast growing tumor as Burkitt-type lymphoma (Tpot = 1 day) should be irradiated using three instead two fractions per day combined with adjuvant or concomitant chemotherapy with a short intervals between cycles.

Sequential combination of radio-chemotherapy (5-fluorouracil, cis-platinum and irradiation) in the management of locally advanced head and neck cancers.

Thirty-seven previously untreated patients with advanced, inoperable head and neck were treated with a sequential courses combining hypofractionated irradiation with chemotherapy (5-fluorouracil and cis-platinum). Each course was repeated every 4 weeks. Tumor response was evaluated and for 15 patients (41%) with a partial or complete regression after 3 radio-chemotherapy courses conventional radiotherapy was added. Eleven percent of all patients were in complete remission at the end of a treatment. This tumor response rate and the 50% rate of pain subside after first course for symptomatic patients contributed for a good palliative effect in the present study. However, the median survival of 7.2 months was considered unsatisfactory.