Probability Of Local Control Research Articles

Po-Poster - 03: A comparison of intensity-modulated radiotherapy versus 3D conformal radiotherapy for prostate cancer patients whose rectal reaction to prior conventional radiotherapy was known

Background and purpose: To evaluate the difference in biological and physical endpoints between intensity-modulated radiotherapy (IMRT) plans and conformal plans for thirteen prostate cancer patients whose rectal reaction to prior radiation therapy was known (five patients experienced Grade 0 late rectal complications, six Grade 1, and two Grade 2). Materials and methods: Conformal plans were generated for each patient with Eclipse version 7.1.59 while the Helios inverse optimization component within Eclipse was applied for computation of the IMRT plans. Physical endpoints applied to compare the IMRT and conformal plans included the target dose statistics (minimum, maximum, and mean dose) as well as dose-volume histogram results for the normal tissues (rectum, bladder, and femoral heads). Biological endpoints used for comparison of the IMRT and conformal plans were tumour control probability (TCP), normal tissue complication probability (NTCP), and probability of uncomplicated local control (P+). Rectal NTCP was computed for both RTOG Grade 3 or lower complications and severe rectal complications (severe proctitis, necrosis, stenosis, and fistula). Results: On average, IMRT increased the TCP by 2.8% and increased the TDI by 7.7%. The average NTCPs for the Grade 3 or lower rectal complications were 15.1% and 4.4% for the conformal and IMRT plans, respectively. For severe rectal complications the average NTCP decreased from 2.1% (conformal) to 1.2% (IMRT). The average P+ increased from 59.4% (conformal) to 69.9% (IMRT). Conclusions: IMRT was found to reduce the rectal NTCP for RTOG Grade 3 or lower complications to ∼0.36 times the NTCP for the conformal plan.

Adjuvant Radiation Therapy for Resectable Retroperitoneal Soft Tissue Sarcoma

In the management of retroperitoneal sarcomas it is necessary to achieve local control to ensure survival. The role of adjuvant radiation therapy (RT), either pre- or postoperative, remains controversial. Outcomes for 40 patients with retroperitoneal sarcoma treated with surgery and postoperative RT (n = 25) or preoperative RT (n = 15) were analyzed for variables prognostic for local control, survival, and associated complications. Patterns of failure for patients treated by resection and postoperative RT were local (n = 4), local and distant (n = 3), and distant (n = 3). The failure patterns for preoperative RT cases were local (n = 2), local and distant (n = 2); and distant (n = 4). Median time to local recurrence in the postoperative and preoperative RT series were 1 year and 2.5 years respectively. The margin status was predictive for local control (P = 0.0065) and survival (P = 0.0012), regardless of treatment sequence. Absolute 5-year survival was 12% with positive margins versus 69% if negative. Histologic grade was indicative of the risk for distant metastasis (low grade 8% vs high grade 64%; P = 0.1373), and significantly predicted 5-year absolute survival (low grade 77% vs high grade 34%; P = 0.0267). Postoperative RT was associated with significant complications (infection, hemorrhage, and bowel obstruction--2 cases each). Compared with the surgery-alone series, adjuvant RT appears to improve the probability of local control. Preoperative RT may be the preferred sequence potentially to improve tumor resectability and local-regional control with less risk of complications than with postoperative RT.

Increased risk of biochemical and local failure in patients with distended rectum on the planning CT for prostate cancer radiotherapy

To retrospectively test the hypothesis that rectal distension on the planning computed tomography (CT) scan is associated with an increased risk of biochemical and local failure among patients irradiated for prostate carcinoma when a daily repositioning technique based on direct prostate-organ localization is not used. This study included 127 patients who received definitive three-dimensional conformal radiotherapy for prostate cancer to a total dose of 78 Gy at The University of Texas M. D. Anderson Cancer Center. Rectal distension was assessed by calculation of the average cross-sectional rectal area (CSA; defined as the rectal volume divided by length) and measuring three rectal diameters on the planning CT. The impact of rectal distension on biochemical control, 2-year prostate biopsy results, and incidence of Grade 2 or greater late rectal bleeding was assessed. The incidence of biochemical failure was significantly higher among patients with distended rectums (CSA >11.2 cm(2)) on the planning CT scan (p = 0.0009, log-rank test). Multivariate analysis indicates that rectal distension and high-risk disease are independent risk factors for biochemical failure, with hazard ratios of 3.89 (95% C.I. 1.58 to 9.56, p = 0.003) and 2.45 (95% C.I. 1.18 to 5.08, p = 0.016), respectively. The probability of residual tumor without evidence of radiation treatment (as scored by the pathologist) increased significantly with rectal distension (p = 0.010, logistic analysis), and a lower incidence of Grade 2 or greater late rectal bleeding within 2 years was simultaneously observed with higher CSA values (p = 0.031, logistic analysis). We found strong evidence that rectal distension on the treatment-planning CT scan decreased the probability of biochemical control, local control, and rectal toxicity in patients who were treated without daily image-guided prostate localization, presumably because of geographic misses. Therefore, an empty rectum is warranted at the time of simulation. These results also emphasize the need for image-guided radiotherapy to improve local control in irradiating prostate cancer.

Treatment of metastatic tumors of the choroid with proton beam irradiation

To describe the clinical outcomes of patients treated by proton beam irradiation for choroidal metastatic tumors. Noncomparative case series. A retrospective chart review was performed on a series of 63 patients (76 eyes) with choroidal metastases treated with proton beam therapy between December 1989 and September 2000. Patients were treated with 2 fractions of 14 cobalt gray equivalents (CGEs) (CGE = proton Gy x relative biological effectiveness 1.1), each using a nonoperative "light-field" technique. Ophthalmologic follow-up was available for 46 patients (55 eyes), with a mean follow-up time of 10 months. The medical record or the Social Security Death Index was used to obtain survival status, which was available in 94% of cases. Tumor regression, recurrence, treatment-associated complications, and visual acuity were evaluated by ophthalmologic examination and ultrasonography. Eye retention and length of survival also were assessed. At the time of ocular diagnosis, 49 patients reported a history of a primary cancer. Median survival time after ocular diagnosis was 16 months through May 2003. Most choroidal metastases were dome shaped (62%) and located at the posterior pole (95%). Mean tumor height was approximately 3.5 mm, and serous retinal detachment was seen in 63% of cases. Eighty-four percent of treated tumors regressed completely within 5 months of treatment, and none of these recurred. Retinal detachment resolved in 82% of patients within 3.8 months after treatment, and visual acuity was preserved or improved in 47% of the patients. Complications occurred in 56% of cases and included madarosis, keratitis, dry eye syndrome, cataract, neovascular glaucoma, chorioretinal atrophy, radiation papillopathy, and radiation maculopathy. None of the treated eyes required enucleation. Proton beam irradiation is a useful therapeutic approach for choroidal metastases; it allows retention of the globe, achieves a high probability of local tumor control, and helps to avoid pain and visual loss. Although complications occur in most cases, many of these are minor and are not associated with a change in function. This modality is accurate and efficient, because it only entails 2 treatment fractions and does not require surgery for tumor localization.

Skull base chordoma

Our purpose was to discuss the optimal treatment and outcomes for patients with skull base chordomas. We reviewed the pertinent literature for this study. Skull base chordomas usually arise in the clivus and are rarely completely resectable. Therefore, most are treated with radiotherapy (RT). Because of the risk of severe late complications, the dose is often limited with conventional photon RT, and the probability of cure is low. Proton RT alone or combined with photon RT (proton/photon RT) offers the advantage of improved dose distribution and the ability to treat the tumor to a higher dose without exceeding normal tissue tolerance. The 10-year local control rate after proton/photon RT is approximately 40% to 50%. The probability of local control is related to minimum tumor dose and dose inhomogeneity. Skull base chordoma is a rare neoplasm that is rarely cured after surgery alone or combined with conventional RT. Proton/photon RT offers the advantage of increasing the tumor dose while minimizing the dose to normal tissues, thus reducing the risk of late complications. The optimal treatment may be photon/proton RT alone or combined with a gross total resection, when feasible.

Adult head and neck soft tissue sarcomas

The purpose was to determine the optimal treatment for adult patients with head and neck soft tissue sarcomas. We conducted a review of the pertinent literature. Local control after surgery alone or combined with radiotherapy was obtained in approximately 60% to 70% of the patients. The probability of local control is influenced by histologic grade, tumor size, and surgical margins. Patients with high-grade tumors and/or positive margins have improved local control if adjuvant radiotherapy is used. Distant metastases occurred in 10% to 30% of patients. The 5-year overall and cause-specific survival rates varied from approximately 60% to 70% and are affected by age, histologic grade, previous treatment of tumor, invasion of deep structures, and adequacy of surgery. The optimal treatment for adult head and neck soft tissue sarcomas is surgery. Adjuvant radiotherapy improves outcomes for those with high-grade tumors and/or positive margins. Radiotherapy alone will cure a small subset of patients with unresectable tumors.

Accelerated radiotherapy for advanced laryngeal cancer

The purpose of this study was to evaluate a single institution's outcome for patients with advanced laryngeal cancer treated with accelerated radiotherapy (RT). Fifty-eight patients with advanced laryngeal cancer (T3/T4N0/N + M0) were treated with curative intent with accelerated RT during the period 1990 − 1998. Patients received radiotherapy alone or with induction chemotherapy. The 5-year local control (LC) and loco-regional control (LRC) probabilities were both 49% for T3 and 75% for T4 tumors. The 5-year disease-free survival probability was 46% and 68% and overall survival probability was 30% and 39% for T3 and T4 tumors respectively. No significant statistical difference in outcome was found, either between T3 and T4 tumors, or between patients who received induction chemotherapy and those who did not. The treatment results for advanced laryngeal cancer at this institution were comparable to those reported in the literature. The results for T3 and T4 were similar. T4 classification alone should not be an exclusion criterion for larynx preservation. Overall survival was poor, partly because of a high incidence of deaths from intercurrent diseases.

Preoperative radiochemotherapy and radical resection for stages II–IV oral and oropharyngeal cancer: outcome of 222 patients

To analyse survival and locoregional control in patients with advanced oral and oropharyngeal squamous cell carcinoma (SCC) after multimodal therapy with preoperative radiochemotherapy (RCT) and radical surgery. We included in this analysis 222 patients who underwent multimodal therapy between 1990 and 2000. Eligible were patients with UICC disease stages II–IV (T2: 33.3%; T3: 12.6%; T4: 54.1%; N0: 45.9%; N1: 17.6%; N2: 33.3%; N3: 3.2%; stage II: 21.1%; stage III: 14.9%; stage IV: 64%). Patients received preoperative radiochemotherapy consisting of Mitomycin C (15–20 mg/m 2, day 1) plus 5-Fluorouracil (750 mg/m 2/24 h-infusion, days 1–5) and concomitant radiotherapy for a total dose of 50 Gy. Radical locoregional en bloc-resection according to the pretherapeutic tumour extension was carried out in all patients. After a median surveillance period of 72.3 months (24–152 months), 131 patients (59%) were alive, and 91 (41%) patients died; 12 (5%) of them died postoperatively, 46 (21%) due to tumour recurrence, and 33 (15%) deaths were not directly related to the primary tumour. Overall survival probability was 76% after 2 years, and 62% after 5 years. Two- and 5-year local control probability were 88 and 81%, respectively. Regarding the high percentage of stage IV disease in the reported patients, the multimodal concept is an effective therapy offering excellent survival and local control probability.

Pretreatment probability model for predicting outcome after intraarterial chemoradiation for advanced head and neck carcinoma.

Concurrent chemoradiation is being used increasingly to treat patients with advanced-stage head and neck carcinoma. In the current study, a clinical nomogram was developed to predict local control and overall survival rates for individual patients who will undergo chemoradiation. Ninety-two consecutive patients with UICC TNM Stage III/IV squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, and supraglottic larynx were treated with selective-targeted chemoradiation (acronym: RADPLAT). All living patients had a minimum follow-up of 2 years. In addition to general factors, the following parameters were analyzed in a multivariable analysis: primary tumor volume, lymph node tumor volume, total tumor volume, lowest involved neck level, comorbidity, pretreatment hemoglobin level, pretreatment weight loss, and unilateral/bilateral intraarterial infusion. Relevant factors for local control and survival were analyzed using the Cox proportional hazards model. At 5 years, the local control and overall survival rates for the whole group were 60% and 38%, respectively. Primary tumor volume (hazard ratio [HR], 1.03; P = 0.01) and unilateral infusion (HR, 5.05; P = 0.004) were found to influence local control significantly. Using tumor volume as a continuous variable, an adjusted risk ratio of 1.026 was found, indicating that each 1-cm(3) increase in volume was associated with a 2.6% decrease in probability of local control. Primary tumor volume (HR, 1.01; P = 0.003), comorbidity (American Society of Anesthesiologists [ASA] physical status 1 vs. > 1; HR, 2.47; P = 0.01), lowest involved neck level (HR, 3.45; P = 0.007), and pretreatment weight loss > 10% (HR, 2.04; P = 0.02) were found to be significant predictors of worse overall survival. Variables from the multivariable analysis were used to develop a nomogram capable of predicting local control and overall survival. Tumor volume was found to play a significant role in predicting local control and overall survival in patients with advanced-stage head and neck carcinoma who were treated with targeted chemoradiation. The nomograms may be useful for pretreatment selection of patients with advanced-stage head and neck carcinoma.

The long-term follow-up on local control of breast carcinoma treated by external beam irradiation plus iridium 192 implant

The long-term follow-up on local control of breast carcinoma treated by external beam irradiation plus iridium 192 implant

Molecular profiles as predictive marker for the effect of overall treatment time of radiotherapy in supraglottic larynx squamous cell carcinomas

Background and purpose Reduction of the overall treatment time of radiotherapy increases the probability of local tumour control, but it does not benefit all patients. Identification of molecular marker profiles may aid in the selection of patients likely to benefit from accelerated radiotherapy. Patients and methods Two hundred and nine patients with SCC of the supraglottic larynx received primary radiotherapy in the randomised DAHANCA trials to 66–68 Gy, 2 Gy/fx but with different overall treatment times of 9.5 week, 6.5 week and 5.5 week. Formalin-fixed paraffin embedded tumour slides were assessed by immunohistochemistry for expression of EGFr, E-cadherin, KI-67 and Bcl-2 and the TP53 mutation profile was determined using PCR-amplification, DHPLC and sequencing. The profiles were established using a hierarchical clustering algorithm with a Bayesian information criterion for cluster number optimisation. Results Full data-set were available for 158 patients and four almost equally sized clusters were identified. One of these clusters differed significantly with respect to local control compared to the other clusters: the cluster ( n=36) characterised by wild type TP53, low expression of E-cadherin and Bcl-2, moderate KI-67 and EGFr, was not influenced by a reduction in the overall treatment time ( P=0.6) whereas the other clusters showed an increase in local control when the overall treatment time of radiotherapy was reduced. This was also partially seen with disease specific survival as the endpoint. Conclusions Molecular marker profiling may aid in the selection of patients that will benefit of a reduction in overall treatment time of radiotherapy in SCC of the supraglottic larynx.

Bladder-conserving surgery and interstitial brachytherapy for lymph node negative transitional cell carcinoma of the urinary bladder: results of a 28-year single institution experience

Background and purpose We retrospectively analyzed results for lymph node negative transitional cell carcinoma of the bladder treated with brachytherapy. Patients and methods From 1975–2002, 58 patients received preoperative external irradiation, partial cystectomy (in 69%), iliac node dissection, and iridium-192. Pathologic stage was: 10 pT1, 41 pT2, and 7 pT3. A median total brachytherapy dose of 60 Gy was delivered to the tumor bed. Results Mean follow-up was 76 months (range, 0.5–296). Tumor stage significantly impacted cause-specific and disease-free survival ( P=0.02). Eight pT1 patients were free of disease and 2 died of other cause. For pT2 patients, 5-year cause-specific and overall survival rates were, respectively, 70% (CI 95%: 53–87) and 60% (CI 95%: 43–77). Three pT3 patients died of cancer. For the pT2 patients, the probability of 5-year local control was 65% (CI 95%: 47–83) and being alive without disease with a functional bladder, 50% (CI 95%: 33–67). Previous transurethral resection (TUR) increased the bladder relapse risk among pT2 patients ( P=0.03). Twelve patients had severe acute complications and 5 had severe late effects. A high dose of external irradiation increased risk of late complications ( P=0.01). Most complications occurred in patients treated before 1985. Conclusions Highly select patients presenting with pT2 tumors less than 5 cm with no history of previous TUR may be successfully treated with low-dose external irradiation, limited partial cystectomy, and interstitial brachytherapy. High-risk pT1 patients may also benefit. Postoperative complications and late side effects are minimized with modern management. We recommend lifelong cystoscopic surveillance, with prompt surgical salvage for recurrence.

Angiocentric T-cell and NK/T-cell lymphomas: radiotherapeutic viewpoints

Purpose To investigate the patterns of local failure and the risk factors predictive of local failure and to establish the dose–response relationships influencing the probability of local control in patients with Stage I and II angiocentric T-cell or natural killer (NK)/T-cell lymphoma who were treated with radiotherapy (RT) alone. Methods and materials We retrospectively reviewed the data from 102 patients with Ann Arbor Stage I and II angiocentric T-cell or NK/T-cell lymphoma who underwent RT alone to a median dose of 45 Gy (range, 20–70 Gy) between 1976 and 1998. The patterns of local failure, risk factors predictive of local failure, dose–response relationships, and survival data were analyzed. Because of the protean feature of local recurrences, the sites of local failure were allocated to one of three categories: true recurrence (TR), marginal recurrence (MR), and elsewhere recurrence (ER). Results Despite a higher complete remission rate (72%) after RT, 60 patients experienced treatment failure, including local failure in 48 (47%), regional failure in 3 (3%), and systemic failure in 28 (27%). The patterns of local failure were TR in 42, MR in 3, and ER in 5 patients. The median time to recurrence for TR/MR was shorter than that for ER (1 month for TR/MR vs. 12 months for ER). Patients with TR/MR had a more unfavorable prognosis than those experiencing ER (2-year survival rate after salvage treatment: 6% for TR/MR vs. 80% for ER; p <0.01). The dose–response curve was sigmoid in shape within the range of 20–54 Gy, which followed the plateau at doses in excess of about 54 Gy. A positive correlation was observed in the dose–response curve for the probability of local control ( p = 0.017, logistic regression analysis). The overall 5-year actuarial survival and local recurrence-free survival rate for all patients was 42% and 53%, respectively. Achievement of complete remission was the most statistically significant risk factor predictive of TR/MR and the most important prognostic factor. Conclusion Our data confirm that local failure remains the major obstacle for patients who receive RT alone and that achievement of complete remission is a particularly important determinant of treatment success. Although dose escalation up to >54 Gy cannot entirely reduce the incidence of TR/MR, we believe it is important to identify an appropriate subset of patients for whom an additional boost dose may be beneficial. Given the high rate of local failure, an investigational approach should be conducted to supplement RT using radiosensitizers or more effective chemotherapeutic agents in future trials.

Potential outcomes of modalities and techniques in radiotherapy for patients with hypopharyngeal carcinoma

Background and purpose To determine potential improvements in treatment outcome for patients with hypopharyngeal carcinoma, T4N0M0, using proton and intensity modulated photon radiotherapy (IMRT) compared to a standard 3D conformal radiotherapy treatment (3D-CRT) in terms of local tumour control probability, TCP, and normal tissue complication probability (NTCP) for the spinal cord and the parotid glands using. Patients and methods Using the three-dimensional treatment-planning system, Helax-TMS™, 5 patients were planned with protons, IMRT, and 3D-CRT plans. The prescribed dose used was 30 fractions×2.39 Gy for the protons and IMRT and 35 fractions×2.00 Gy for 3D-CRT. The treatment plans were evaluated using dose volume data and dose response models were used to calculate TCP and NTCP. The target volumes were delineated to spare the parotid glands. A dose escalation was made for protons and IMRT using NTCP constraints to the spinal cord. Results On average, protons and IMRT increase TCP by 17% compared to 3D-CRT. For the spinal cord NTCP values are zero for all methods and patients. Average NTCP values for the parotid glands were >90% for 3D-CRT and significantly lower for protons and IMRT varying from 43–65%. The average parotid gland dose was 33 Gy for the protons, 38 Gy for IMRT and 48 Gy for 3D-CRT. Conclusions Protons and IMRT gave a significant TCP increase compared to 3D-CRT while no significant difference between protons and IMRT was found. Protons generally show lower non-target tissue doses, which indicates a possibility for further dose escalation. Large individual dose differences between protons and IMRT for parotid glands indicate that some patients may benefit more from protons and others from IMRT.

Primary Tumor Control in Patients With Stage 3/4 Unfavorable Neuroblastoma Treated With Tandem Double Autologous Stem Cell Transplants

To assess the efficacy and toxicity of local radiotherapy in achieving local control in patients with stage 4 or high-risk stage 3 neuroblastoma treated with induction chemotherapy and tandem stem cell transplants. Fifty-two children with stage 4 or high-risk stage 3 neuroblastoma were treated on a standardized protocol that included five cycles of induction chemotherapy, surgical resection of the primary tumor when feasible, local radiotherapy, and then consolidation with tandem myeloablative cycles with autologous peripheral blood stem cell rescue. Local radiotherapy (10.5-18 Gy) was administered to patients with gross or microscopic residual disease prior to the myeloablative cycles. Thirty-seven patients received local radiotherapy to the primary tumor or primary tumor bed. Two patients with unknown primaries each received radiotherapy to single, unresectable, bulky metastatic sites. The second of the myeloablative regimens included 12 Gy of total body irradiation. Of the 52 consecutively treated patients analyzed, 44 underwent both transplants, 6 underwent a single transplant, and 2 progressed during induction. Local radiotherapy did not prolong recovery of hematopoiesis following transplants, did not increase peritransplant morbidity, and did not prolong the hospital stay compared with patients who had not received local radiotherapy. Local control was excellent. Of 11 patients with disease recurrence after completion of therapy, 9 failed in bony metastatic sites 3 to 21 months after the completion of therapy, 1 recurred 67 months following therapy in the previously bulky metastatic site that had been irradiated, and 1 had local recurrence concurrent with distant progression 15 months following the second transplant. The three-year event-free survival was 63%, with a median follow-up of 29.5 months. The actuarial probability of local control was 97%. The use of induction chemotherapy, aggressive multimodality therapy for the primary tumor, followed by tandem myeloablative cycles with stem cell transplant in patients with stage 4 or high risk stage 3 neuroblastoma has resulted in acceptable toxicity, a very low local recurrence risk, and an improvement in survival.

Pulsed ultrasound measurements of depth and regression of basal cell carcinomas after photodynamic therapy: relationship to probability of 1-year local control

The regression of clinical basal cell carcinoma (BCC) after photodynamic therapy (PDT) is poorly understood, but is potentially important when, as is increasingly the case, a second treatment is contemplated. High-frequency pulsed ultrasound provides noninvasive information on skin and lesion thickness. To relate pulsed ultrasound measurements before and after PDT to the probability of local control of BCC by PDT. Skin thickness and lesion thickness were measured by 20-MHz pulsed ultrasound in 181 patients diagnosed as having BCC. Maximal lesion thickness was determined by repeatedly sampling the BCCs. Measurements were made immediately prior to PDT with aminolaevulinic acid plus 630 nm visible light, and then at 1, 6 and 12 months. Skin thickness in individual patients did not vary with time in this study (mean +/- SD 2.3 +/- 0.6 mm; P = 0.8). In contrast, BCC mean +/- SD maximal thickness 4-6 weeks after PDT was significantly smaller than pretreatment (0.6 +/- 0.8 mm vs. 1.3 +/- 0.8 mm; P < 0.001). The overall probability of 1-year local control fell from 85% when only BCCs </= 1.5 mm thick were considered, to 75% when BCCs up to 3 mm were included. Ultrasound measurement of maximal pretreatment BCC thickness strongly predicts the probability of local control, defined clinically, at 1 year after a single PDT treatment. The degree of regression at 4-6 weeks is additionally predictive.

15 Tumour local-control probability prediction (TLCP) & other radiobiological issues in the use of IMRT

15 Tumour local-control probability prediction (TLCP) & other radiobiological issues in the use of IMRT

Incorporating clinical measurements of hypoxia into tumor local control modeling of prostate cancer: Implications for the α/β ratio

Background and purpose The recently obtained low value of ∼1.5 for the α/β of prostate cancer has led us to reexamine the optimal prostate tumor biology parameters, while taking into account everything known about the radiation response of prostate clonogens for use in a predictive dose–response model. Methods and materials Averages of the literature values of the α- and β-inactivation coefficients for human prostate cancer cell lines were calculated. A robust tumor local control probability (TLCP) model was used that required average α and β, as well as σ α, for the interpatient variation in single-hit killing (α). Median P o 2 values ≤1 mm Hg in the prostates of Fox Chase Cancer Center brachytherapy patients had been found in 21% of 115 cases. The oxygen enhancement ratios of 1.75 and 3.25 for α- and β-inactivation, respectively, measured for tumor cells in vitro, were incorporated into the TLCP model, together with a clonogen density of ∼10 5 cells/cm 3. Severe hypoxia and radioresistance were estimated for a proportion of tumors that was increased with PSA level. Results For asynchronous human prostate cell lines irradiated in air, α mean was 0.26 ± 0.07 (standard error) Gy −1, σ α = 0.06 Gy −1, and β mean was 0.0312 Gy −2 ± 0.0064 (standard error) Gy −2. The TLCP data indicated that most tumors that contained aerobic cells would be cured, whereas most tumors that contained hypoxic cells would not be cured by total doses of 76 to 80 Gy. Clinical response data from the literature for external beam dose escalation, stratified by PSA value, and for low-dose-rate brachytherapy, were well predicted by the model, where the α/β ratio was 8.5 and 15.5 for well-oxygenated and hypoxic clonogens, respectively. Conclusions Neither α/β ratio nor clonogen number need be extremely low to explain the response of prostate cancer to brachytherapy and external beam therapy, contradicting other recent analyses. It is strongly suggested that severe hypoxia in the prostates of certain patients limits the overall cancer cure rate by conventional radiation therapy.

Hemoglobin as an Independent Prognostic Factor in the Radiotherapy of Head and Neck Tumors

The purpose of this study was to analyze the prognostic value of baseline hemoglobin levels before radiotherapy in patients with head and neck tumors. In a retrospective study with a median follow-up of 43 months, we analyzed the results of 214 patients irradiated for head and neck cancer between January 1, 1990 and January 1, 1998 (180 men and 34 women; median age 58 years). The treatment concept consisted in adjuvant radiotherapy in 58 patients, 77 patients received definitive radiochemotherapy, 42 patients definitive radiotherapy, and 37 patients reirradiation for in-field recurrence. Baseline hemoglobin values were divided in four groups of the same patient number (quartiles). Several known prognostic factors like sex, age, tumor stage, histologic grading, performance status, and treatment scheme were analyzed for their influence on overall and event-free survival and correlated with pretreatment hemoglobin values (Kaplan-Meier method). In addition, univariate und multivariate logistic regression analyses were carried out to evaluate the effect of baseline hemoglobin on response rates. The median survival (event-free survival) of all patients amounted to 15 months (10 months). 25%, 50%, and 75% of patients had hemoglobin values < 11.2 g/dl, < 12.7 g/dl, and < 13.9 g/dl, respectively. In the univariate analysis, the following variables were significant prognostic factors for overall/event-free survival (log-rank test): treatment concept (p < 0.001/p < 0.001), tumor stage (p < 0.001/p < 0.001), general condition (p < 0.001/p < 0.001), and pretreatment hemoglobin (p = 0.014/p = 0.05). Multivariate analysis (Cox) proved these parameters to be independent of each other. In addition, response rate after radiation showed a strong association between hemoglobin and local control probability (p = 0.02). In this retrospective analysis, baseline hemoglobin level was shown to be an independent significant prognostic factor in radiotherapy of head and neck cancer patients. Therefore, the value of tumor anemia as a prognostic factor should be emphasized more.

Single-fraction vs. fractionated linac-based stereotactic radiosurgery for vestibular schwannoma: a single-institution study

Purpose In this single-institution trial, we investigated whether fractionated stereotactic radiation therapy is superior to single-fraction linac-based radiosurgery with respect to treatment-related toxicity and local control in patients with vestibular schwannoma. Methods and materials All 129 vestibular schwannoma patients treated between 1992 and June 2000 at our linac-based radiosurgery facility were analyzed with respect to treatment schedule. Dentate patients were prospectively selected for a fractionated schedule of 5 × 4 Gy and later on 5 × 5 Gy at the 80% isodose in 1 week with a relocatable stereotactic frame. Edentate patients were prospectively selected for a nonfractionated treatment of 1 × 10 Gy and later on 1 × 12.5 Gy at 80% isodose with an invasive stereotactic frame. Both MRI and CT scans were made in all 129 patients within 1 week before treatment. All patients were followed yearly with MRI and physical examination. Results A fractionated schedule was given to 80 patients and a single fraction to 49 patients. Mean follow-up time was 33 months (range: 12–107 months). There was no statistically significant difference between the single-fraction group and the fractionated group with respect to mean tumor diameter (2.6 vs. 2.5 cm) or mean follow-up time (both 33 months). Only mean age (63 years vs. 49 years) was statistically significantly different ( p = 0.001). Outcome differences between the single-fraction treatment group and the fractionated treatment group with respect to 5-year local control probability (100% vs. 94%), 5-year facial nerve preservation probability (93% vs. 97%), and 5-year hearing preservation probability (75% vs. 61%) were not statistically significant. The difference in 5-year trigeminal nerve preservation (92% vs. 98%) reached statistical significance ( p = 0.048). Conclusion Linac-based single-fraction radiosurgery seems to be as good as linac-based fractionated stereotactic radiation therapy in vestibular schwannoma patients, except for a small difference in trigeminal nerve preservation rate in favor of a fractionated schedule.