Extraneural metastases from cranial meningioma: a case report

Extracranial metastases from brain meningiomas is a rare, but well-documented entity. Metastases occur mostly in the lungs, pleura and liver, but may also affect lymph nodes and bones. We report here on a patient who was treated for an atypical brain meningioma with multiple surgeries and multiple sessions of stereotactic radiosurgery with good control of his brain disease. Thirteen years after diagnosis, he developed bilateral large sacroiliac and abdominal metastases

Inter-institutional comparison of personalized risk assessments for second malignant neoplasms for a 13-year-old girl receiving proton versus photon craniospinal irradiation

Children receiving radiotherapy face the probability of a subsequent malignant neoplasm (SMN). In some cases, the predicted SMN risk can be reduced by proton therapy. The purpose of this study was to apply the most comprehensive dose assessment methods to estimate the reduction in SMN risk after proton therapy vs. photon therapy for a 13-year-old girl requiring craniospinal irradiation (CSI). We reconstructed the equivalent dose throughout the patient’s body from therapeutic and stray radiation and applied SMN incidence and mortality risk models for each modality. Excluding skin cancer, the risk of incidence after proton CSI was a third of that of photon CSI. The predicted absolute SMN risks were high. For photon CSI, the SMN incidence rates greater than 10% were for thyroid, non-melanoma skin, lung, colon, stomach, and other solid cancers, and for proton CSI they were non-melanoma skin, lung, and other solid cancers. In each setting, lung cancer accounted for half the risk of mortality. In conclusion, the predicted SMN risk for a 13-year-old girl undergoing proton CSI was reduced vs. photon CSI. This study demonstrates the feasibility of inter-institutional whole-body dose and risk assessments and also serves as a model for including risk estimation in personalized cancer care

Low- and middle-income countries can reduce risks of subsequent neoplasms by referring pediatric craniospinal cases to centralized proton treatment centers

Few children with cancer in low- and middle-income countries (LMICs) have access to proton therapy. Evidence exists to support replacing photon therapy with proton therapy to reduce the incidence of secondary malignant neoplasms (SMNs) in childhood cancer survivors. The purpose of this study was to estimate the potential reduction in SMN incidence and in SMN mortality for pediatric medulloblastoma (MB) patients in LMICs if proton therapy were made available to them. For nine children of ages 2-14 years, we calculated the equivalent dose in organs or tissues at risk for radiogenic SMNs from therapeutic and stray radiation for photon craniospinal irradiation (CSI) in a LMIC and proton CSI in a high-income country. We projected the lifetime risks of SMN incidence and SMN mortality for every SMN site with a widely-used model from the literature. We found that the average total lifetime attributable risks of incidence and mortality were very high for both photon CSI (168% and 41%, respectively) and proton CSI (88% and 26%, respectively). SMNs having the highest risk of mortality were lung cancer (16%), non-site-specific solid tumors (16%), colon cancer (5.9%), leukemia (5.4%), and for girls breast cancer (5.0%) after photon CSI and non-site-specific solid tumors (12%), lung cancer (11%), and leukemia (4.8%) after proton CSI. The risks were higher for younger children than for older children and higher for girls than for boys. The ratios of proton CSI to photon CSI of total risks of SMN incidence and mortality were 0.56 (95% CI, 0.37-0.75) and 0.64 (95% CI, 0.45-0.82), respectively, averaged over this sample group. In conclusion, proton therapy has the potential to lessen markedly subsequent SMNs and SMN fatalities in survivors of childhood MB in LMICs, for example, through regional centralized care. Additional methods should be explored urgently to reduce therapeutic-field doses in organs and tissues at risk for SMN, especially in the lungs, colon, and breast tissues

Accumulation of the common mitochondrial DNA deletion induced by ionizing radiation

AbstractPoint mutations and deletions in mitochondrial DNA (mtDNA) accumulate as a result of oxidative stress, including ionizing radiation. As a result, dysfunctional mitochondria suffer from a decline in oxidative phosphorylation and increased release of superoxides and other reactive oxygen species (ROS). Through this mechanism, mitochondria have been implicated in a host of degenerative diseases. Associated with this type of damage, and serving as a marker of total mtDNA mutations and deletions, the accumulation of a specific 4977-bp deletion, known as the common deletion (Δ-mtDNA4977), takes place. The Δ-mtDNA4977 has been reported to increase with age and during the progression of mitochondrial degeneration. The purpose of this study was to investigate whether ionizing radiation induces the formation of the common deletion in a variety of human cell lines and to determine if it is associated with cellular radiosensitivity. Cell lines used included eight normal human skin fibroblast lines, a radiosensitive non-transformed and an SV40 transformed ataxia telangiectasia (AT) homozygous fibroblast line, a Kearns Sayre Syndrome (KSS) line known to contain mitochondrial deletions, and five human tumor lines. The Δ-mtDNA4977 was assessed by polymerase chain reaction (PCR). Significant levels of Δ-mtDNA4977 accumulated 72 h after irradiation doses of 2, 5, 10 or 20 Gy in all of the normal lines with lower response in tumor cell lines, but the absolute amounts of the induced deletion were variable. There was no consistent dose–response relationship. SV40 transformed and non-transformed AT cell lines both showed significant induction of the deletion. However, the five tumor cell lines showed only a modest induction of the deletion, including the one line that was deficient in DNA damage repair. No relationship was found between sensitivity to radiation-induced deletions and sensitivity to cell killing by radiation

A phase II randomized trial comparing radiotherapy with concurrent weekly cisplatin or weekly paclitaxel in patients with advanced cervical cancer

<p>Abstract</p> <p>Purpose/Objective</p> <p>This is a prospective comparison of weekly cisplatin to weekly paclitaxel as concurrent chemotherapy with standard radiotherapy for locally advanced cervical carcinoma.</p> <p>Materials/Methods</p> <p>Between May 2000 and May 2004, 31 women with FIGO stage IB2-IVA cervical cancer or with postsurgical pelvic recurrence were enrolled into this phase II study and randomized to receive on a weekly basis either 40 mg/m²Cisplatin (group I; 16 patients) or 50 mg/m²paclitaxel (group II; 15 patients) concurrently with radiotherapy. Median total dose to point A was 74 Gy (range: 66-92 Gy) for group I and 66 Gy (range: 40-98 Gy) for group II. Median follow-up time was 46 months.</p> <p>Results</p> <p>Patient and tumor characteristics were similar in both groups. The mean number of chemotherapy cycles was also comparable with 87% and 80% of patients receiving at least 4 doses in groups I and II, respectively. Seven patients (44%) of group I and 8 patients (53%) of group II developed tumor recurrence. The Median Survival time was not reached for Group I and 53 months for group II. The proportion of patients surviving at 2 and 5 years was 78% and 54% for group I and 73% and 43% for group II respectively.</p> <p>Conclusions</p> <p>This small prospective study shows that weekly paclitaxel does not provide any clinical advantage over weekly cisplatin for concurrent chemoradiation for advanced carcinoma of the cervix.</p

Influence of initial presentation on treatment outcome of clinically localized prostate cancer treated by definitive radiation therapy

Purpose : The increasing proportion of early stage prostate cancer diagnosed by various early detection methods together with reports espousing watchful waiting as a management option raise the possibility that patients may be selected for surveillance according to their initial presentation. Methods and Materials : The outcome for 427 men with clinical stages T1 to T4 localized prostate cancer treated with radiation therapy was evaluated according to their presentation: elevated prostate-specific antigen (PSA) level; abnormal digital rectal examination; or, urologic symptomatology. Results : With a median follow-up of 30 months, there were no significant differences in disease outcome according to initial presentation. The actuarial incidence of relapse at 5 years was: PSA-detected (54 patients), 24%; digital rectal-detected (173 patients) 29%; and, symptom-detected (200 patients) 31% ( p = 0.79). Likewise, there were no significant differences in the incidence of postradiation rising PSA profiles among the three groups. The actuarial incidence of relapse and/or rising PSA at 5 years was: PSA-detected 35%; digital rectal-detected 42%; symptom-detected, 48% ( p = 0.72). On the other hand, T-stage, Gleason grade, pretreatment PSA, pretreatment acid phosphatase, and transurethral resection in T3 T4 disease were each highly correlated with outcome. In multivariate proportional hazards regression pretreatment PSA ( p = 0.0003), Gleason grade ( p = 0.045), and transurethral resection in T3 T4 disease ( p = 0.0562) correlated with outcome, but initial presentation did not ( p = 0.25). Conclusion : The absence of a prognostic gradient, good to bad, from PSA-detected through digital rectal-detected to symptom-detected cancer suggests that the initial presentation of patients with localized prostate cancer is not a valid basis for selecting watchful waiting vs. initial treatment

The T classification of clinically localized prostate cancer. An appraisal based on disease outcome after radiation therapy

Background. This study was performed to evaluate the use of the 1992 International Union Against Cancer (UICC)/American Joint Committee on Cancer (AJCC) T categories for localized prostate cancer treated with radiation therapy and to compare the prognostic power of this system with the Whitmore‐Jewett scheme. Methods. The outcome for 427 men with Stages A2‐C or T1a‐T4b prostate cancers, followed for a mean of 32 months after treatment, was evaluated for relapse or rising prostate‐specific antigen (PSA) levels, disease relapse, metastatic failure, and local recurrence relative to the two staging systems. Univariate and multivariate analysis was used to compare the two staging systems. The T categories were based on digital rectal examination. Results. At 5 years, the actuarial incidence of relapse or rising PSA level was as follows: Stage A2, 29%; Stage B, 41%; Stage C, 62%. The corresponding results according to T category were as follows: T1a, 0%; T1b, 37%; T1c, 23%; T2a, 39%; T2b, 38%; T2c, 42%; T3a, 53%; T3c, 68%; T4b, greater than 75%. Too few patients were in the T3b and T4a categories. The following five‐category grouping was significantly superior prognostically to the Whitmore‐Jewett system: T1a, T1c, T1b/T2, T3, T4. The actuarial incidences of relapse or rising PSA at 5 years were as follows: T1a, 0%; T1c, 23%; T1b/T2, 41%; T3, 61%; and T4, 75%. No differences were evident within the T2 or T3 categories. Conclusions. The current UICC/AJCC system appears to be a valid method for categorizing a primary prostate carcinoma. This system defines a greater number of meaningful tumor categories and is prognostically superior to the traditional Whitmore‐Jewett scheme

Prophylactic Cranial Irradiation in Patients With Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

BackgroundWe systematically reviewed the literature for trials addressing the efficacy of prophylactic cranial irradiation (PCI) in patients with non-small-cell lung cancer (NSCLC) treated with a curative intent.MethodsRandomized controlled trials (RCT) comparing PCI to no PCI in patients with NSCLC treated with a curative intent were eligible for inclusion. We searched EMBASE, MEDLINE, PubMed, and CENTRAL between 1946 and July 2016. We also received continual search alerts from PubMed through September 2017. Search terms included “non-small-cell lung carcinoma,” “cranial irradiation,” and “randomized controlled trials.” We conducted meta-analyses using random-effects models for relative measures of treatment effect for the incidence of brain metastasis, overall survival (OS), and disease-free survival (DFS). We used Parmar’s methodology to derive hazard ratios (HR) when not explicitly stated in RCTs. We narratively synthesized data for the impact of PCI on quality of life (QoL) and neurocognitive function (NCF). We assessed the quality of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation methodology.ResultsOut of 3,548 citations captured by the search strategy, we retained 8 papers and 1 abstract, reporting on 6 eligible trials. Patients who received PCI had a significant reduction in the risk of developing brain metastases as compared with patients who did not [relative risk (RR) = 0.37; 95% confidence interval (CI): 0.26–0.52; moderate quality evidence]. However, there was no OS benefit (HR = 1.08, 95% CI: 0.90–1.31; moderate quality evidence). Sensitivity analysis excluding older studies did not show substantively different findings. DFS was reported in the two most recent trials that included only stage III patients. There was significant improvement in DFS with PCI (HR = 0.67; 95% CI: 0.46–0.98; high quality evidence). Two studies that reported on QoL reported no statistically significant differences. There was no significant difference in NCF decline in the only study that reported on this outcome, except in immediate and delayed recall, as assessed by the Hopkins Verbal Learning Test.ConclusionThere is moderate quality evidence that the use of PCI in patients with NSCLC decreases the risk of brain metastases, but does not provide an OS benefit. However, data limited to stage III patients suggests that PCI improves DFS, with no effect on QoL