Total neoadjuvant therapy in rectal cancer: the evidence and expectations.

Current management of locally advanced rectal cancer achieves high cure rates, distant metastatic spread being the main cause of patients' death. Total neoadjuvant therapy (TNT) employs (chemo)radiotherapy and combined chemotherapy prior to surgery to improve the treatment outcomes. TNT has been shown to reduce significantly distant metastases, increase disease-free survival by 5 - 10% in 3 years, and finally also overall survival (≈ 5% in 7 years). It proved to double the rate of pathologic complete responses, making it an attractive strategy for non-operative management to avoid permanent colostomy in patients with distal tumors. In addition, it endorses adherence to the therapy due to better tolerance and, potentially, shortens its overall duration. A number of questions related to TNT remain currently unresolved including the indications, preferred radiotherapy and chemotherapy regimens, their sequence, timing of surgery, and role of adjuvant therapy. A stratified approach may be the optimal way to go.

Impact of comorbidity scores and lifestyle factors in curative radiotherapy in laryngeal cancer.

PURPOSE: The principal goal of treatment of laryngeal cancer is to eliminate a tumour while preserving laryngeal function with radio(chemo)therapy being the mainstay of treatment. The aim of this report is to present the influence of comorbidities and lifestyle factors on treatment outcomes in our cohort of patients. METHODS: During the period 2009-2018, curative radio(chemo)therapy for laryngeal cancer was performed on 189 patients. RESULTS: The median OS was 50.8 months, with a mean PFS of 96.5 months, mean LC of 101.4 months and a median follow-up of 38.1 months. Acute and late treatment toxicity grade 3-4 was observed in 39.2% patients and 10.1% patients, respectively. A significant effect on overall survival was confirmed for the baseline PS (performance status), severity of weight loss, baseline haemoglobin values, history of alcohol abuse, marital status and comorbidities according to the Charlson Comorbidity Index, as well as the ACE-27 and ASA scores. CONCLUSIONS: In our cohort of patients treated with radio(chemo)therapy for laryngeal cancer, we found good therapeutic results and an acceptable side-effect profile. Statistically significant predictors of overall survival were the baseline PS, weight loss, anaemia, associated comorbidities, history of alcohol abuse and marital status.

Tumour volume and radiotherapy prolongation in locally advanced head and neck cancer patients treated with radical IMRT.

AIMS: The relationship of tumour volume, radiotherapy treatment time and other prognostic factors affecting prognosis was evaluated. METHODS: 184 patients with locally advanced head and neck cancer were treated with radical intensity modulated radiotherapy (IMRT) and compared retrospectively. RESULTS: In the multivariate analysis the overall survival was dependent on gross tumour volume (GTV), clinical stage (CS), radiotherapy treatment time (RTT) and p16 status. Local control was influenced by GTV, overall RTT and age. DFS was significantly affected by GTV, CS, RTT, p16 status and concomitant chemotherapy (CHT). CONCLUSIONS: The tumour volume and the radiotherapy treatment time were the most significant prognostic factors with the best outcomes in patients with GTV ≤ 55 cc and RTT ≤ 48 days (mean LC 8.1, DFS 7.1 and OS 6.4 years) and worst outcomes with GTV > 55 cc and RTT >48 days (mean LC 4.4, mean DFS 3.2 and mean OS 2.6 years).

Use of positron emission tomography/ computed tomography in the initial staging of head and neck squamous cell carcinoma: Accuracy in evaluation of the primary site of the tumor, metastases to cervical lymph nodes, and distant metastases.

AIM: Our study aimed to evaluate the use of positron emission tomography/computed tomography (PET/CT) in the initial staging of head and neck squamous cell carcinoma (HNSCC), including assessment of local and distant spread of the disease. We also aimed to compare the accuracy of PET/CT in the evaluation of human papillomavirus (HPV) positive and HPV-negative oropharyngeal carcinoma. MATERIAL AND METHODS: This single-center, prospective study was conducted between August 2016 and September 2021. A total of 198 patients with HNSCC who underwent PET/CT within the primary staging were included. We compared PET/CT results with histological findings. We calculated the accuracy, sensitivity, specificity, and positive and negative predictive values to assess the primary tumor, cervical lymph nodes, and distant metastases. RESULTS: PET/CT showed a high success rate (32%) in revealing the primary site of carcinoma of unknown primary (CUP). The accuracy of PET/CT in displaying the primary tumor, cervical lymph node metastases, and distant metastases was 89.4%, 85.4%, and 87.4%, respectively. The method provided high sensitivity but lower specificity in all three areas. Specifically, PET/CT showed low specificity in the assessment of small tumors (75%), metastatic involvement of cervical lymph nodes (69.6%), and HPV-positive oropharyngeal carcinoma (55.6%). CONCLUSIONS: The high accuracy of PET/CT to identify distant metastases and whole-body staging in one diagnostic step accelerated primary staging and resulted in earlier commencement of therapy. However, it also led to an overestimation of clinical findings and thus to extensive surgical treatment, especially in patients with small tumors, metastatic involvement of cervical lymph nodes, and HPV- positive oropharyngeal carcinoma. PET/CT is also useful for CUP diagnostics.

Determining priority risk groups for compensation of treatment breaks in radical radiotherapy in patients with locally advanced head and neck cancer.

PURPOSE: Prolongation of radiotherapy worsens the results of treatment of head and neck squamous cell carcinoma (HNSCC). The purpose of this study was to identify the prognostic factors most affected by the prolongation of treatment. METHODS: 184 patients with locally advanced HNSCC were treated with curative chemo-radiation using SIB-IMRT from 2008 to 2016 and the influence of radiotherapy time (RTT) in groups of patients according to prognostic factors was retrospectively evaluated. RESULTS: Median overall survival (OS) was 45 months, median disease-free survival (DFS) was 41 months and median local control (LC) was not reached (mean LRC 68 months). In the multivariate analysis the radiotherapy prolongation negatively affected the LC in stage IV patients, T3/T4, in neck nodes positive disease, in oropharyngeal and oral cavity cancers, after neoadjuvant chemotherapy and in men. The RTT effect on DFS was significant in stage IV patients, patients with neck nodes positive disease and oropharyngeal cancer. RTT prolongation decreased OS within the groups of stage IV and grade 3 tumours. CONCLUSION: Prolonged RTT was associated with worsened OS and LRC, especially in stage IV patients and/or neck node positive disease and/or oropharyngeal cancer and we recommend that these patients should be prioritized in treatment gap compensation in radical radiotherapy for locally advanced HNSCC.

Radiotherapy dose limit for uterus fertility sparing in curative chemoradiotherapy for rectal cancer.

AIMS: Curative sphincter sparing radiotherapy is a treatment option for early rectal cancer. There are many methods developed for fertility preservation in young patients treated with pelvic radiotherapy. Pregnancy rates after radiotherapy are dependent on the radiation dose to ovaries and uterus. Data on outcomes of total body irradiation suggest a pregnancy is possible following 12-14 Gy TBI, despite elevated rates of preterm deliveries and other complications. METHODS: We report a case of full-term delivery of twins after curative chemoradiotherapy for anorectal adenocarcinoma T2 N0 M0 with the total dose 58.6 Gy. The patient underwent laparoscopic laterocranial ovarian transposition before radiotherapy. RESULTS: Long term complete remission was achieved after treatment. Although a spontaneous conception was not successful, the patient underwent an in vitro fertilisation procedure with donor eggs and conceived twins 10 years after the radiotherapy treatment. The mean dose to the uterus was 16 Gy and to the uterine cervix 35 Gy. She reached a full-term pregnancy and delivered two healthy babies by caesarean section at a gestational age of 38 weeks, weighing 2420 g and 2220 g. CONCLUSION: This is the first case report of the successful pregnancy following sphincter sparing curative pelvic radiotherapy for rectal cancer. Furthermore it allows us to propose an increased limit dose to the uterus enabling fertility sparing beyond the limits achieved from total body irradiation series with 12-14 Gy and accept 16 Gy as uterine body (35 Gy for uterine cervix) limit for IMRT treatment planning in young patients asking for maintaining fertility potential.

Effectiveness of transoral laser microsurgery for precancerous lesions and early glottic cancer guided by analysis of voice quality.

BACKGROUND: The purpose of this study was to show our comparison of the quality of voice obtained after superficial transoral endoscopic cordectomies (types I, II, and III) according to the European Laryngological Society classification versus the more extended cordectomy (types IV and V) among patients with glottic precancerous lesions or early glottic cancer. METHODS: Sixty-two patients underwent vocal assessment after cordectomy (types I-V) for dysplasia, Tis, T1a, T1b, and T2 lesions. RESULTS: Cordectomy (types I-III) had good vocal outcomes. Cordectomy (types IV-V) showed less favorable outcomes, p < .005 in common parameters of voice range profile and symmetry in stroboscopy after cordectomy (types IV-V), with significant voice handicap index. Recurrences were found in 4 patients with T1b and T2 cancer. Two cases were managed by a higher type of cordectomy, and the other 2 by total laryngectomy. CONCLUSION: Effect of transoral laser microsurgery on quality of voice depends on the type of cordectomy and the site of the lesion.

A new survival score for patients with brain metastases who received whole-brain radiotherapy (WBRT) alone.

BACKGROUND AND PURPOSE: Survival scores for patients with brain metastasis exist. However, the treatment regimens used to create these scores were heterogeneous. This study aimed to develop and validate a survival score in homogeneously treated patients. MATERIALS AND METHODS: Eight-hundred-and-eighty-two patients receiving 10 × 3Gy of WBRT alone were randomly assigned to a test group (N=441) or a validation group (N=441). In the multivariate analysis of the test group, age, performance status, extracranial metastasis, and systemic treatment prior to WBRT were independent predictors of survival. The score for each factor was determined by dividing the 6-month survival rate (in %) by 10. Scores were summed and total scores ranged from 6 to 19 points. Patients were divided into four prognostic groups. RESULTS: The 6-month survival rates were 4% for 6-9 points, 29% for 10-14 points, 62% for 15-17 points, and 93% for 17-18 points (p<0.001) in the test group. The survival rates were 3%, 28%, 54% and 96%, respectively (p<0.001) in the validation group. CONCLUSIONS: Since the 6-month survival rates in the validation group were very similar to the test group, this new score (WBRT-30) appears valid and reproducible. It can help making treatment choices and stratifying patients in future trials.

Dose-escalation of whole-brain radiotherapy for brain metastasis in patients with a favorable survival prognosis.

BACKGROUND: Patients with brain metastases who have a favorable survival prognosis may benefit from intensive treatments, including neurosurgery and radiosurgery. However, many patients cannot receive such treatments, and whole-brain radiotherapy (WBRT) alone is their only option. The most common WBRT schedule is 30 grays (Gy) in 10 fractions. In this retrospective study, the authors investigated whether these patients benefit from a dose escalation beyond 30 Gy. METHODS: Data from 109 patients who received 30 Gy in 10 fractions were compared with 75 patients who received 40 Gy in 20 fractions. All patients had a favorable survival prognosis. Both groups were compared for local control (LC) and overall survival (OS). Subgroup analyses were performed for patients who had less radiosensitive tumors (N = 27) and for other patients (N = 157). RESULTS: The LC rate at 1 year was 28% after 30 Gy and 44% after 40 Gy (P = .064). On multivariate analysis, the 40 Gy dose was associated with improved LC (P = .047). The survival rate at 1 year was 50% after 30 Gy and 61% after 40 Gy (P = .007). On multivariate analysis, the 40 Gy dose was associated with improved OS (P = .008). On subgroup analysis of patients who had less radiosensitive tumors, the 1-year LC rate was 7% after 30 Gy and 38% after 40 Gy (P = .031); and the 1-year OS rate was 40% and 73%, respectively (P = .008). On subgroup analysis of patients who had other tumor types, the 1-year LC rate was 31% after 30 Gy and 45% after 40 Gy (P = .26); and the 1-year OS rate was 52% and 59%, respectively (P = .08). CONCLUSIONS: Escalation of the WBRT dose beyond 30 Gy resulted in better outcomes, particularly for patients who had less radiosensitive tumors.

Shorter-course whole-brain radiotherapy for brain metastases in elderly patients.

PURPOSE: Many patients with brain metastases receive whole-brain radiotherapy (WBRT) alone. Using 10 × 3 Gy in 2 weeks is the standard regimen in most centers. Regarding the extraordinarily poor survival prognosis of elderly patients with multiple brain metastases, a shorter WBRT regimen would be preferable. This study compared 10 × 3 Gy with 5 × 4 Gy in elderly patients (≥65 years). METHODS AND MATERIALS: Data from 455 elderly patients who received WBRT alone for brain metastases were retrospectively analyzed. Survival and local (= intracerebral) control of 293 patients receiving 10 × 3 Gy were compared with 162 patients receiving 5 × 4 Gy. Eight additional potential prognostic factors were investigated including age, gender, Karnofsky performance score (KPS), primary tumor, number of brain metastases, interval from tumor diagnosis to WBRT, extracerebral metastases, and recursive partitioning analysis (RPA) class. RESULTS: The 6-month overall survival rates were 29% after 5 × 4 Gy and 21% after 10 × 3 Gy (p = 0.020). The 6-month local control rates were 12% and 10%, respectively (p = 0.32). On multivariate analysis, improved overall survival was associated with KPS ≥ 70 (p < 0.001), only one to three brain metastases (p = 0.029), no extracerebral metastasis (p = 0.012), and lower RPA class (p < 0.001). Improved local control was associated with KPS ≥ 70 (p < 0.001), breast cancer (p = 0.029), and lower RPA class (p < 0.001). CONCLUSIONS: Shorter-course WBRT with 5 × 4 Gy was not inferior to 10 × 3 Gy with respect to overall survival or local control in elderly patients. 5 × 4 Gy appears preferable for the majority of these patients.

Scoring systems to estimate intracerebral control and survival rates of patients irradiated for brain metastases.

PURPOSE: To create and validate scoring systems for intracerebral control (IC) and overall survival (OS) of patients irradiated for brain metastases. METHODS AND MATERIALS: In this study, 1,797 patients were randomly assigned to the test (n = 1,198) or the validation group (n = 599). Two scoring systems were developed, one for IC and another for OS. The scores included prognostic factors found significant on multivariate analyses. Age, performance status, extracerebral metastases, interval tumor diagnosis to RT, and number of brain metastases were associated with OS. Tumor type, performance status, interval, and number of brain metastases were associated with IC. The score for each factor was determined by dividing the 6-month IC or OS rate (given in percent) by 10. The total score represented the sum of the scores for each factor. The score groups of the test group were compared with the corresponding score groups of the validation group. RESULTS: In the test group, 6-month IC rates were 17% for 14-18 points, 49% for 19-23 points, and 77% for 24-27 points (p < 0.0001). IC rates in the validation group were 19%, 52%, and 77%, respectively (p < 0.0001). In the test group, 6-month OS rates were 9% for 15-19 points, 41% for 20-25 points, and 78% for 26-30 points (p < 0.0001). OS rates in the validation group were 7%, 39%, and 79%, respectively (p < 0.0001). CONCLUSIONS: Patients irradiated for brain metastases can be given scores to estimate OS and IC. IC and OS rates of the validation group were similar to the test group demonstrating the validity and reproducibility of both scores.

Short-course whole-brain radiotherapy (WBRT) for brain metastases due to small-cell lung cancer (SCLC).

OBJECTIVE: Many patients with brain metastases due to SCLC have a poor survival prognosis. The most common treatment is whole-brain radiotherapy (WBRT). This retrospective study compares short-course WBRT with 5x4Gy in 1 week to standard WBRT with 10x3Gy in 2 weeks. METHODS: Forty-four SCLC patients receiving WBRT with 5x4Gy were compared to 102 patients receiving 10x3Gy for survival (OS) and local (intracerebral) control (LC). Seven further potential prognostic factors were investigated: age, gender, Karnofsky Performance Score (KPS), number of brain metastases, extracerebral metastases, interval from tumor diagnosis to WBRT, RPA (Recursive Partitioning Analysis) class. RESULTS: After 5x4Gy, 12-month OS was 15%, versus 22% after 10x3Gy (p=0.69). On multivariate analysis, improved OS was associated with age or=70 (p<0.001), <4 brain metastases (p=0.011), and RPA class 1 (p<0.001). 12-month LC was 34% after 5x4Gy versus 25% after 10x3Gy (p=0.32). On multivariate analysis, improved LC was associated with KPS >or=70 (p<0.001), <4 brain metastases (p=0.027), and RPA class 1 (p<0.001). CONCLUSION: In patients with brain metastases due to SCLC, short-course WBRT with 5x4Gy provided similar outcomes as 10x3Gy and appears preferable, particularly for patients with poor estimated survival.

The International Testicular Cancer Linkage Consortium: a clinicopathologic descriptive analysis of 461 familial malignant testicular germ cell tumor kindred.

OBJECTIVES: Familial aggregation of testicular germ cell tumor (TGCT) has been reported, but it is unclear if familial TGCT represents a unique entity with distinct clinicopathologic characteristics. Here we describe a collection of familial TGCT cases from an international consortium, in an effort to elucidate any clinical characteristics that are specific to this population. MATERIALS AND METHODS: Families with >or=2 cases of TGCT enrolled at 18 of the sites participating in the International Testicular Cancer Linkage Consortium were included. We analyzed clinicopathologic characteristics of 985 cases from 461 families. RESULTS: A majority (88.5%) of families had only 2 cases of TGCT. Men with seminoma (50% of cases) had an older mean age at diagnosis than nonseminoma cases (P = 0.001). Among individuals with a history of cryptorchidism, TGCT was more likely to occur in the ipsilateral testis (kappa = 0.65). Cousin pairs appeared to represent a unique group, with younger age at diagnosis and a higher prevalence of cryptorchidism than other families. CONCLUSIONS: Clinicopathologic characteristics in these familial TGCT cases were similar to those generally described for nonfamilial cases. However, we observed a unique presentation of familial TGCT among cousin pairs. Additional studies are needed to further explore this observation.

Surgical resection followed by whole brain radiotherapy versus whole brain radiotherapy alone for single brain metastasis.

PURPOSE: To compare the outcome of surgical resection followed by whole brain radiotherapy (WBRT) with WBRT alone in patients treated for single brain metastasis. METHODS AND MATERIALS: The data from 195 patients with single brain metastases were retrospectively evaluated. Of the 195 patients, 99 underwent resection of the metastasis followed by WBRT and 96 underwent WBRT alone. Seven additional potential prognostic factors were investigated: age, gender, Eastern Cooperative Oncology Group performance score, tumor type, interval between initial tumor diagnosis and WBRT, extracranial metastases, and recursive partitioning analysis class. Both treatment groups were well balanced for these factors. RESULTS: On multivariate analysis, improved survival was associated with resection (relative risk [RR], 1.20; 95% confidence interval [CI], 1.11-1.31; p < 0.001), lower recursive partitioning analysis class (RR, 1.58; 95% CI, 1.22-2.06; p < 0.001), age < or = 61 years (RR, 1.79; 95% CI, 1.23-2.61; p = 0.002), Eastern Cooperative Oncology Group performance score of 0-1 (RR, 2.47; 95% CI, 1.70-3.59; p < 0.001), and the absence of extracranial metastases (RR, 1.99; 95% CI, 1.41-2.79; p < 0.001). Improved local control was associated with resection (RR, 1.25; 95% CI, 1.11-1.41; p < 0.001) and age < or = 61 years (RR, 1.77; 95% CI, 1.09-2.88; p = 0.020). Improved brain control distant from the original site was associated with lower recursive partitioning analysis class (RR, 1.65; 95% CI, 1.03-2.69; p < 0.035), age < or = 61 years (RR, 1.81; 95% CI, 1.12-2.96; p = 0.016), and the absence of extracranial metastases (RR, 2.42; 95% CI, 1.52-3.88; p < 0.001). Improved control within the entire brain was associated with surgery (RR, 1.24; 95% CI, 1.12-1.38; p < 0.001) and age < or = 61 years (RR, 1.83; 95% CI, 1.21-2.77; p = 0.004). CONCLUSION: In patients with a single brain metastasis, the addition of resection to WBRT improved survival, local control at the original metastatic site, and control within the entire brain, but did not prevent the development of new brain metastases distant to the original site.

Comparison of short-course versus long-course whole-brain radiotherapy in the treatment of brain metastases.

BACKGROUND AND PURPOSE: Whole-brain radiotherapy (WBRT) is the most common treatment for brain metastases. Most of these patients have a poor survival prognosis. Therefore, a short radiation program is preferred, if it provides a similar outcome as longer programs. This study compares 20 Gy in five fractions (treatment time: 1 week) to longer programs, with higher doses including 30 Gy in ten fractions (2 weeks) and 40 Gy in 20 fractions (4 weeks). PATIENTS AND METHODS: Data regarding 1,085 patients treated with WBRT for brain metastases were retrospectively analyzed. 387 patients received 20 Gy in five fractions, and 698 patients received higher doses (30 Gy in ten fractions, n = 527, or 40 Gy in 20 fractions, n = 171). In addition, eight potential prognostic factors were investigated including age, sex, Karnofsky Performance Score (KPS), tumor type, interval from tumor diagnosis to WBRT, number of brain metastases, extracranial metastases, and recursive partitioning analysis (RPA) class. Subgroup analyses were performed for each RPA class individually. RESULTS: The WBRT schedule had no significant impact on survival (p = 0.415). On multivariate analysis, improved survival was significantly associated with age < or = 60 years (risk ratio [RR]: 1.28; p < 0.001), KPS > or = 70 (RR: 1.73; p = 0.002), lack of extracranial metastases (RR: 1.27; p = 0.007), interval from tumor diagnosis to WBRT > 8 months (RR: 1.19; p = 0.011), and lower RPA class (RR: 1.56; p < 0.001). The subgroup analyses for each RPA class did not reveal a significant association between WBRT schedule and survival. CONCLUSION: Short-course WBRT with 20 Gy in five fractions is preferable for most patients, because it is associated with similar survival as longer programs and is less time-consuming.

Analysis of the DND1 gene in men with sporadic and familial testicular germ cell tumors.

A base substitution in the mouse Dnd1 gene resulting in a truncated Dnd protein has been shown to be responsible for germ cell loss and the development of testicular germ cell tumors (TGCT) in the 129 strain of mice. We investigated the human orthologue of this gene in 263 patients (165 with a family history of TGCT and 98 without) and found a rare heterozygous variant, p. Glu86Ala, in a single case. This variant was not present in control chromosomes (0/4,132). Analysis of the variant in an additional 842 index TGCT cases (269 with a family history of TGCT and 573 without) did not reveal any additional instances. The variant, p. Glu86Ala, is within a known functional domain of DND1 and is highly conserved through evolution. Although the variant may be a rare polymorphism, a change at such a highly conserved residue is characteristic of a disease-causing variant. Whether it is disease-causing or not, mutations in DND1 make, at most, a very small contribution to TGCT susceptibility in adults and adolescents.

Whole-brain radiotherapy with 20 Gy in 5 fractions for brain metastases in patients with cancer of unknown primary (CUP).

BACKGROUND: Whole brain radiotherapy (WBRT) is the most common treatment for brain metastases. Survival of patients with cancer of unknown primary (CUP) presenting with brain metastases is extremely poor. A radiation program with a short overall treatment time (short-course RT) would be preferable to longer programs if it provides similar outcomes. This study compares short-course RT with 20 Gy in 5 fractions (5 x 4 Gy) given over 5 days to longer programs in CUP patients. PATIENTS AND METHODS: Data regarding 101 CUP patients who received either short course WBRT (n=34) with 5 x 4 Gy or long-course WBRT (n=67) with 10 x 3 Gy given over 2 weeks or 20 x 2 Gy given over 4 weeks for brain metastases were analyzed retrospectively. Six additional potential prognostic factors were investigated: age, gender, Karnofsky performance score (KPS), number of brain metastases, extracranial metastases, RPA-(Recursive Partitioning Analysis-)class. RESULTS: On univariate analysis, the radiation program was not associated with survival (p=0.88) nor intracerebral control (p=0.36). Improved survival was associated with KPS >or= 70 (p<0.001), absence of extracranial metastases (p<0.001), and RPA-class 1 (p<0.001). On multivariate analyses, KPS (risk ratio [RR]: 4.55; p<0.001), extracranial metastases (RR: 1.70; p=0.018), and RPA-class (RR: 2.86; p<0.001) maintained significance. On univariate analysis, KPS (p<0.001) and RPA-class (p<0.001) were significantly associated with intracerebral control. On multivariate analyses, KPS (RR: 2.72; p<0.001) and RPA-class (RR: 2.09; p<0.001) remained significant. CONCLUSION: Short-course WBRT with 5 x 4 Gy provided similar intracerebral control and survival as longer programs for the treatment of brain metastases in CUP patients. 5 x 4 Gy appears preferable because it is more convenient for patients.

Evaluation of 2 whole-brain radiotherapy schedules and prognostic factors for brain metastases in breast cancer patients.

BACKGROUND: The majority of breast cancer patients with brain metastases receive whole-brain radiotherapy (WBRT) and have a survival of only a few months. A short WBRT regimen would be preferable if it provides survival that is similar to that achieved with longer programs. This retrospective study compared survival and local control within the brain resulting from short-course WBRT with longer programs in 207 breast cancer patients. METHODS: Sixty-nine patients treated with 5 fractions of 4 grays (Gy) each given within 5 days were compared with 138 patients treated with 10 fractions of 3 Gy each given over 2 weeks or 20 fractions of 2 Gy each given over 4 weeks. Six additional potential prognostic factors were investigated: age, Karnofsky performance score (KPS), number of brain metastases, the presence of extracranial metastases, interval from tumor diagnosis to WBRT, and recursive partitioning analysis (RPA) class. RESULTS: On univariate analysis, the WBRT regimen was not found to be associated with survival (P=.254) or local control (P=.397). Improved survival was associated with a KPS>70 (P<.001), single brain metastasis (P=.023), the absence of extracranial metastases (P<.001), and lower RPA class (P<.001). On multivariate analysis, which was performed without RPA class because this is a confounding variable, KPS (relative risk [RR] of 4.00; P<.001) and the presence of extracranial metastases (RR of 1.54; P=.024) maintained statistical significance. On univariate analysis, local control was associated with KPS (P<.001) and RPA class (P<.001). On multivariate analysis, local control was found to be associated with a KPS>70 (RR of 5.75; P<.001). CONCLUSIONS: Short-course WBRT with 5 fractions of 4 Gy each resulted in survival and local control that were similar to longer programs in breast cancer patients with brain metastases. The dose of 5 fractions of 4 Gy each appears preferable for the majority of these patients because it is less time consuming and more convenient.

Reduction of overall treatment time in patients irradiated for more than three brain metastases.

PURPOSE: Patients with multiple brain metastases usually receive whole brain radiotherapy (WBRT). A dose of 30 Gy in 10 fractions (10 x 3 Gy) in 2 weeks is the standard treatment in many centers. Regarding the poor survival of these patients, a shorter RT regimen would be preferable if it provides a similar outcome as that with 10 x 3 Gy. This study compared 20 Gy in five fractions (5 x 4 Gy) within 5 days to 10 x 3 Gy. METHODS AND MATERIALS: Data from 442 patients treated with WBRT for multiple brain metastases were retrospectively analyzed. Survival and local control within the brain of 232 patients treated with 5 x 4 Gy were compared with the survival and local control within the brain of 210 patients treated with 10 x 3 Gy. Seven additional potential prognostic factors were investigated: age, gender, Karnofsky performance score, tumor type, interval from tumor diagnosis to RT, extracranial metastases, and recursive partitioning analysis class. RESULTS: On univariate analysis, the WBRT program was not associated with survival (p = 0.29) or local control (p = 0.07). On multivariate analyses, improved survival was associated with a lower recursive partitioning analysis class (p < 0.001), age or=70 (p = 0.015), and the absence of extracranial metastases (p = 0.005). Improved local control was associated with a lower recursive partitioning analysis class (p < 0.001), Karnofsky performance score >or=70 (p < 0.001), and breast cancer (p = 0.043). Grade 3 acute toxicity rates were not significantly different between 5 x 4 Gy and 10 x 3 Gy. CONCLUSIONS: Shorter course WBRT with 5 x 4 Gy was associated with similar survival and local control as "standard" WBRT with 10 x 3 Gy in patients with more than three brain metastases. The 5 x 4-Gy regimen appears preferable for most of these patients, because it is less time consuming and more convenient for patients than the 10 x 3-Gy regimen.

Two radiation regimens and prognostic factors for brain metastases in nonsmall cell lung cancer patients.

BACKGROUND: Nonsmall cell lung cancer (NSCLC) patients with brain metastases usually receive whole-brain radiotherapy (WBRT). Most of these patients survive for only a few months. A short course of WBRT would be preferable to longer regimens if it could provide similar survival. This retrospective study of NSCLC patients compared longer treatment programs with short-course WBRT with 5 x 4 Gy given during 5 days. METHODS: Data from 404 NSCLC patients treated with WBRT for brain metastases were retrospectively analyzed. The 140 patients who received 5 x 4 Gy given in 5 days were compared for survival with 264 patients who received either 10 x 3 Gy given in 2 weeks or 20 x 2 Gy given in 4 weeks. Seven further potential prognostic factors were investigated for survival including age, sex, Karnofsky performance score (KPS), number of brain metastases, extracranial metastases, interval from tumor diagnosis to WBRT, and RPA (recursive partitioning analysis) class. RESULTS: The WBRT regimen was not associated with survival (P = .55). On multivariate analysis, age < 60 years (vs > or =60 years, P = .020), KPS > or =70 (vs KPS < 70, P < .001), interval from tumor diagnosis to WBRT > 12 months (vs < or =12 months, P = .007), no extracranial metastases (P < .001), and RPA class 1 (vs RPA class 2 vs RPA class 3, P = .007) were significantly associated with improved survival. CONCLUSIONS: Short-course WBRT with 5 x 4 Gy appeared preferable for most NSCLC patients, as it was associated with survival similar to longer WBRT programs, and the short course was less time consuming.