A number of cell death pathways have been recognized. Though apoptosis and autophagy have been well characterized, programmed
necrosis has recently received attention and may provide clinical ...alternatives to suppress resistant tumors. Necrosis is primarily
characterized by large-scale permeabilization, swelling, and rupture of cell membranes and the release of pro-inflammatory
cytokines. Traditionally, necrosis in cancer cells has been indicative of poor prognoses, as chronic inflammation was found
to encourage tumor growth. Yet, many antitumor effects associated with necrosis have been discovered in certain settings,
such as the formation of an effective antitumor immune response. In this way, finding ways to attenuate the pro-tumor effects
of necrosis while engaging the antitumor pathways via drugs, radiation, and sensitization may prove valuable as a clinical
focus for the future. We hypothesize that the use of Bcl-2 inhibitors may enhance necrotic death characterized by inflammation
and antitumor immunity. In this article, we briefly review apoptosis and autophagy and reason how necrosis may be a suitable
alternative therapeutic endpoint. We then highlight novel inhibitors of Bcl-2 that may provide clinical application of our
hypothesis in the future. Mol Cancer Ther 2009;8(6):1421–9
Abstract Introduction African Americans experience the highest burden of cancer incidence and mortality in the United States and have been persistently less likely to receive interventional care, ...even when such care has been proven superior to conservative management by randomized controlled trials. The presence of disparities in access to radiation therapy (RT) for African American cancer patients has rarely been examined in an expansive fashion. Methods and materials An extensive literature search was performed using the PubMed database to examine studies investigating disparities in RT access for African Americans. Results A total of 55 studies were found, spanning 11 organ systems. Disparities in access to RT for African Americans were most prominently study in cancers of the breast (23 studies), prostate (7 studies), gynecologic system (5 studies), and hematologic system (5 studies). Disparities in RT access for African Americans were prevalent regardless of organ system studied and often occurred independently of socioeconomic status. Fifty of 55 studies (91%) involved analysis of a population-based database such as Surveillance, Epidemiology and End Result (SEER; 26 studies), SEER-Medicare (5 studies), National Cancer Database (3 studies), or a state tumor registry (13 studies). Conclusions African Americans in the United States have diminished access to RT compared with Caucasian patients, independent of but often in concert with low socioeconomic status. These findings underscore the importance of finding systemic and systematic solutions to address these inequalities to reduce the barriers that patient race provides in receipt of optimal cancer care.
Background
Tumor treating fields (TTF) harness magnetic fields to induce apoptosis in targeted regions. A 2015 landmark randomized phase III trial of newly diagnosed glioblastoma (GBM) patients ...demonstrated TTF + temozolomide to be superior to temozolomide alone. Given these results, we sought to assess practice patterns of providers in TTF utilization for GBM.
Methods
A survey was administered to practices in the United States self-identifying as specializing in radiation oncology, medical oncology, neuro-oncology, neurosurgery, and/or neurology. Responses were collected anonymously; analysis was performed using Fisher’s exact test.
Results
A total of 106 providers responded; a minority (36%) were in private practice. Regarding case volume, 82% treated at least six high-grade gliomas/year. The provider most commonly certified to offer TTF therapy to GBM patients was the neuro-oncologist (40%), followed by the radiation oncologist (34%); 31% reported no TTF-certified physician in their practice. TTF users were more likely to have high volume, and be aware of TTF inclusion in National Comprehensive Cancer Network (NCCN) guidelines (p < 0.05).
Conclusions
More than 80% of TTF for GBM in the United States is performed by groups who treat at least six high-grade gliomas per year; unfortunately more than 30% were in practices bereft of anyone certified to offer TTF therapy. These results indicate that there remains fertile soil for TTF therapy nationwide to be introduced into practices for GBM treatment. Providers seeking to refer newly diagnosed GBM patients for TTF should seek out practices with TTF user-associated characteristics to ensure optimal access for their patients.
•The long-term stroke rate of photon-based SRS for meningioma is 1.7%.•The proton-based RT long-term stroke rate for meningioma is 20.5%.•SRS for meningioma has a comparable stroke risk profile to ...observation.
A recent randomized study of fractionated radiation therapy (RT) examining 44 subtotally resected/recurrent benign meningioma patients revealed that at median follow-up of 17.1 years, the risk of stroke following proton-photon RT was 20.5%; the average stroke developed 5.6 years following RT completion (Sanford et al., 2017). This stroke risk is up to 10 times higher than the 2–6% rate expected for the general population of ages 40–79 (Mozaffarian et al., 2015). The stroke rate following single-fraction stereotactic radiosurgery (SRS) has not been previously studied in meningioma patients.
A PubMed database search for relevant articles examining SRS for meningioma with minimum mean/median follow-up of six years was undertaken. Stroke rate was assessed either from direct description in manuscripts, or from extrapolating post-SRS complications from reported clinical examinations (i.e. hemiparesis/weakness, pituitary dysfunction following treatment of cavernous sinus lesions). Results were then culled to determine an overall stroke rate.
Fourteen studies met inclusion criteria; 1431 patients received photon-based SRS for meningioma with a sufficient long-term follow-up. Median/mean follow-up ranged from 75 to 144 months. Operative resection prior to SRS occurred in 769/1377 patients (55.8%) for whom surgical history was reported. Twenty-four patients suffered a stroke following SRS, yielding a rate of 1.7%.
The long-term stroke rate following single-fraction photon-based SRS for benign meningioma was 1.7%, more than twelve times lower than for fractionated proton-photon RT and comparable to that expected for the general population. The majority of patients underwent resection prior to SRS. These findings indicate that for patients with benign meningioma desiring to avoid the high stroke risk of fractionated proton-photon RT, SRS has a comparable stroke risk profile to observation. Such findings are pertinent for radiation oncology, neuro-oncology, and neurosurgery management of these patients.
Despite Level IIB evidence from a nationwide analysis that there are no racial differences in operative morbidity or mortality of ATL for this patient population 2, African-Americans remain ...significantly less likely than Caucasians to receive ATL for pharmacoresistant unilateral mesial temporal lobe epilepsy (MTLE) 3. Unlike diseases such as acoustic neuroma, where evidence that African-Americans are significantly more likely than Caucasians to suffer in-hospital operative mortality following surgical resection makes the noninvasive nature of SRS appealing 6, the absence of racial mortality disparities in ATL for MTLE and the results of the ROSE trial indicate that African-Americans with MTLE should be triaged by epileptologists towards and not away from surgical resection, particularly given its proven Level I evidence track record of superiority over medical and now radiosurgical alternatives in achieving Engel class I outcomes 1,2,4. The far superior seizure freedom rate of SRS (52% at three years using 24 Gy) versus optimal medical therapy alone (8% at one year) for MTLE from Level I evidence is an indication that regardless of race/ethnicity, patients who are unable to safely tolerate operative intervention should be referred for SRS rather than continued AED management 1,4. Because SRS doses of less than 24 Gy have been associated with failed seizure control (with potentially fatal consequences) 7, epileptologists should ensure that any inoperable patient they refer for SRS receives 24 Gy as their treatment dose.
For young adults with acute lymphoblastic leukemia, pediatric‐based regimens are likely to provide the following when compared to hyper‐CVAD regimens: better disease control, less hospitalization ...time, diminished acute toxicities, decreased financial cost, more quality‐adjusted life years, and fewer adverse late effects, such as infertility, myelodysplasia, and second malignant neoplasms. There are also reasons to expect less cardiac and cognitive dysfunction after pediatric regimens. The improved quality and quantity of life associated with pediatric regimens renders them preferable to hyper‐CVAD regimens for the treatment of Philadelphia‐negative B‐precursor or T‐cell acute lymphoblastic leukemia and lymphoblastic lymphoma in young adults.
To conduct a retrospective review of 168 consecutively treated locally advanced head-and-neck cancer (LAHNC) patients treated with intensity-modulated radiotherapy (IMRT)/chemotherapy, to determine ...the rate and risk factors for developing hypothyroidism.
Intensity-modulated radiotherapy was delivered in 33 daily fractions to 69.3 Gy to gross disease and 56.1 Gy to clinically normal cervical nodes. Dose-volume histograms (DVHs) of IMRT plans were used to determine radiation dose to thyroid and were compared with DVHs using conventional three-dimensional radiotherapy (3D-RT) in 10 of these same patients randomly selected for replanning and with DVHs of 16 patients in whom the thyroid was intentionally avoided during IMRT. Weekly paclitaxel (30 mg/m(2)) and carboplatin area under the curve-1 were given concurrently with IMRT.
Sixty-one of 128 evaluable patients (47.7%) developed hypothyroidism after a median of 1.08 years after IMRT (range, 2.4 months to 3.9 years). Age and volume of irradiated thyroid were associated with hypothyroidism development after IMRT. Compared with 3D-RT, IMRT with no thyroid dose constraints resulted in significantly higher minimum, maximum, and median dose (p < 0.0001) and percentage thyroid volume receiving 10, 20, and 60 Gy (p < 0.05). Compared with 3D-RT, IMRT with thyroid dose constraints resulted in lower median dose and percentage thyroid volume receiving 30, 40, and 50 Gy (p < 0.005) but higher minimum and maximum dose (p < 0.005).
If not protected, IMRT for LAHNC can result in higher radiation to the thyroid than with conventional 3D-RT. Techniques to reduce dose and volume of radiation to thyroid tissue with IMRT are achievable and recommended.
Optimal acoustic neuroma (AN) management involves choosing between three treatment modalities: microsurgical excision, radiation, or observation with serial imaging. The reported in-hospital ...mortality rate of surgery for AN in the United States is 0.5%. However, there has yet to be a nationwide examination of the AN surgery mortality rate encompassing the period beyond initial hospital discharge.
The National Cancer Data Base (NCDB) from 2004 to 2013 identified AN patients receiving surgery. Multivariate logistic regression assessed 30-day operative mortality, adjusting for several variables including patient age, race, sex, income, geographic region, primary payer for care, tumor size, and medical comorbidities.
Ten thousand one hundred thirty six patients received surgery as solitary treatment for AN. Mortality at 30 days postoperatively occurred in 49 patients (0.5%); only a Charlson/Deyo score of 2 (odds ratio OR = 6.6;95% confidence interval CI = 2.6-16.6; p = 0.002) was predictive of increased mortality. No other patient demographic including African-American race, minimum age of 65 or government insurance was predictive of 30-day operative mortality.
The 30-day mortality rate following surgery for AN is 1 of 200 (0.5%), equivalent to the established in-hospital operative mortality rate, and 2.5 times higher than the cumulative assessment from single-center studies. No patient demographic other than increasing medical comorbidities reached significance in predicting 30-day operative mortality. The nearly identical rates of 30-day and in-hospital mortality from separate nationwide analyses indicate that nearly all of the operative mortality occurs before initial postoperative discharge from the hospital. This mortality rate provides a framework for comparing the true risks and benefits of surgery versus radiation or observation for AN.
Tumor-treating fields (TTFs) have become an important, evidence-based modality in the treatment of glioblastoma (GBM). In patients requiring cardiac pacemakers, TTF therapy is complicated by ...theoretical concerns regarding possible electrical interaction between the devices.
A 57-year-old man with past medical history of sick sinus syndrome requiring cardiac pacemaker implantation suffered an acute neurologic change associated with a left parieto-occipital lesion, which was found to be GBM. After completion of guideline-concordant chemoradiation, he chose to undergo TTF therapy. Because of the absence of cardiac symptoms and the theoretical risk of far-field sensing by the pacemaker of the TTF device (potentially resulting in pacemaker inhibition), the pacemaker was turned off before receiving TTF. Following TTF implementation, the patient responded well; he remains alive more than 25 months following his GBM diagnosis, exceeding the median 20.9-month survival of the recently completed phase III TTF randomized clinical trial for newly diagnosed GBM. Furthermore, he has exhibited neither cardiac morbidity nor adverse scalp reactions to TTF therapy.
The first reported case of successful TTF administration in a GBM patient with a previously implanted cardiac pacemaker may allay the concerns of neuro-oncologists, cardiologists, radiation oncologists, and all certified TTF prescribers regarding the applicability of TTF in suitable candidates with preexisting cardiac pacemakers. This case indicates that TTF therapy may be efficacious in patients with indwelling magnetic resonance image−conditional cardiac pacemakers turned to the off position and that physical removal of the pacemaker is not necessary before starting TTF.
•MRI-conditional cardiac pacemakers do not preclude tumor treating fields (TTFs).•TTF is efficacious for glioblastoma patients with indwelling pacemakers turned off.•Physical removal of an indwelling pacemaker is not necessary before starting TTF.
Highlights • African-American race triaged from surgery towards acoustic neuroma observation. • Elderly age triaged from surgery towards acoustic neuroma radiation or observation. • Integrated ...networks triaged towards surgery and away from observation. • Comprehensive cancer centers triaged towards radiation for acoustic neuroma. • Medicaid insurance triaged towards surgery and away from radiation/observation.
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