Use of Amifostine for Cytoprotection during Radiation Therapy: A Review.

BACKGROUND: Radiation therapy is a cornerstone of the therapeutic modalities used in modern oncology. However, it is sometimes limited in its ability to achieve optimal tumor control by radiation-induced normal tissue toxicity. In delivering radiation therapy, a balance must be achieved between maximizing the dose to the tumor and minimizing any injury to the normal tissues. Amifostine was the first Food and Drug Administration (FDA)-approved clinical radiation protector intended to reduce the impact of radiation on normal tissue, lessening its toxicity and potentially allowing for increased tumor dose/control. Despite being FDA-approved almost 20 years ago, Amifostine has yet to achieve widespread clinical use. SUMMARY: A thorough review of Amifostine's development, mechanism of action, and current clinical status were conducted. A brief history of Amifostine is given, from its development at Walter Reid Institute of Research to its approval for clinical use. The mechanism of action of Amifostine is explored. The results of a complete literature review of all prospective randomized trials to date involving the use of Amifostine in radiation therapy are presented. The results are arranged by treatment site and salient findings discussed. Side effects and complications to consider in using Amifostine are reviewed. Key Messages: Amifostine has been explored as a radiation protectant in most radiation treatment sites. Studies have demonstrated efficacy of Amifostine in all treatment sites reviewed, but results are heterogeneous. The heterogeneity of studies looking at Amifostine as a clinical radiation protectant has precluded a definitive answer on its efficacy. Complicating its clinical use is its toxicity and delivery requirements. Amifostine has largely fallen out of use with the advent of intensity modulated radiation therapy (IMRT). However, side effects with IMRT remain a challenge and concern. The use of Amifostine in the IMRT era has been poorly explored and is worthy of future study.

Do African-American men need separate prostate cancer screening guidelines?

BACKGROUND: In 2012, the United States Preventative Services Task Force issued new guidelines recommending that male U.S. residents, irrespective of race, no longer be screened for prostate cancer. In African American men, the incidence of prostate cancer is almost 60 % higher and the mortality rate is two to three times greater than in Caucasians. The purpose of this study is to reduce African American men's prostate cancer burden by demonstrating they need separate screening guidelines. METHODS: We performed a PubMed search using the keywords: African American, Prostate cancer, Outcomes, Molecular markers, Prostate-specific Antigen velocity, PSA density, and to derive data relevant to our hypothesis. RESULTS: In our literature review, we identified several aspects of prostate cancer that are different in Caucasian and African American men. These included prostate cancer incidence and outcome, the clinical course of the disease, serum PSA levels, genetic differences, and social barriers. It's also important to note that the USPSTF guidelines were based on two studies, one of which reported that only 4 % of its participants were African American. The other did not report demographic information, but used participants from seven European countries with small African American populations. CONCLUSION: Given the above, we conclude that separate prostate cancer screening guidelines are greatly necessary to help save the lives of African Americans.

Prostate Cancer Screening Guidelines for African American Veterans: A New Perspective.

BACKGROUND: Prostate cancer is the most common form of cancer, other than skin cancers, in American men and the second leading cause of cancer deaths. In 2012, the US Preventative Task Force recommended against the prostate specific antigen-based screening for prostate cancer, regardless of race or age, due to overtreatment of low-risk disease and lack of impact on disease outcomes. In African-American men, however, the incidence of prostate cancer is almost 60% higher and the mortality rate is two- to three-times greater than that of Caucasian men. In the subpopulation of African-American veterans, many have been exposed to chemicals that increase incidence of high-risk prostate cancer. The yearly total number of veterans with prostate cancer based on quantification is 3471.9, and the total number of annual prostate cancer deaths is 556. Considering these facts, we examine whether or not it is appropriate to screen African-American veteran males for prostate cancer. Previously, we reviewed data on African-Americans in the general population. We concluded that new guidelines needed to be implemented for screening African-Americans. Here we review the pertinent issues related to African-American veterans. METHODS: We performed a PubMed and Google Scholar search using the keywords: African-American veteran, prostate cancer, mortality, PSA density, molecular markers, and Agent Orange. The articles that were relevant to the clinical, molecular, social, and health policy aspects of the diagnosis and treatment of prostate cancer in African-American veterans were analyzed. The data was then summarized. RESULTS: After surveying the literature, we found several areas where the African-American veteran population differed from their Caucasian counterparts. These areas were incidence, clinical course, social differences, PSA levels, mortality rate, and molecular markers. A subset of the veteran population was also exposed to Agent Orange, which has been shown to increase the incidence of aggressive forms of prostate cancer. Lastly, the current USPTF guidelines recommending against prostate cancer screening were based on patient cohorts containing disproportionately low numbers of African-Americans, limiting their extension to the African-American veteran population. CONCLUSION: After reviewing and summarizing the literature, we contend that a need exists to develop and implement more targeted prostate cancer screening guidelines for African-American veterans.

Oligometastatic head and neck cancer: Comprehensive review.

There are limited data available regarding the management of oligometastatic squamous cell carcinoma of the head and neck (SCCHN) patients, and no consensus guidelines are available. The objective is to review the available literature for the management of oligometastatic SCCHN. Articles were selected from English Medline literature between 1995 and 2018, searched by using the keywords: oligometastatic SCCHN/metastasectomy/stereotactic body radiation treatment (SBRT). With the available data, oligometastatic SCCHN patients appear to behave differently and tend to have a better prognosis than those with widespread metastases. Retrospective evidence suggests that the aggressive treatment of the primary disease and local treatment of the metastatic sites improves survival in oligometastatic SCCHN at diagnosis. The definitive treatment of the distant metastatic sites using metastasectomy or SBRT correlates with better survival in oligorecurrent patients. Oligometastatic SCCHN patients may have a better prognosis if treated aggressively.

Malignant peripheral nerve sheath tumor of nasal cavity and paranasal sinus with 13 years of follow-up-A case report and review of literature.

Although extremely rare, sarcomas including malignant peripheral nerve sheath tumors should be considered in the differential diagnosis of sino-nasal tract lesions. Long-term cure is possible through definitive operative management followed by adjuvant therapy.

Upcoming imaging concepts and their impact on treatment planning and treatment response in radiation oncology.

For 2018, the American Cancer Society estimated that there would be approximately 1.7 million new diagnoses of cancer and about 609,640 cancer-related deaths in the United States. By 2030 these numbers are anticipated to exceed a staggering 21 million annual diagnoses and 13 million cancer-related deaths. The three primary therapeutic modalities for cancer treatments are surgery, chemotherapy, and radiation therapy. Individually or in combination, these treatment modalities have provided and continue to provide curative and palliative care to the myriad victims of cancer.Today, CT-based treatment planning is the primary means through which conventional photon radiation therapy is planned. Although CT remains the primary treatment planning modality, the field of radiation oncology is moving beyond the sole use of CT scans to define treatment targets and organs at risk. Complementary tissue scans, such as magnetic resonance imaging (MRI) and positron electron emission (PET) scans, have all improved a physician's ability to more specifically identify target tissues, and in some cases, international guidelines have even been issued. Moreover, efforts to combine PET and MR to define solid tumors for radiotherapy planning and treatment evaluation are also gaining traction.Keeping these advances in mind, we present brief overviews of other up-and-coming key imaging concepts that appear promising for initial treatment target definition or treatment response from radiation therapy.

Analysis of a real time group consensus peer review process in radiation oncology: an evaluation of effectiveness and feasibility.

BACKGROUND: Peer review systems within radiation oncology are important to ensure quality radiation care. Several individualized methods for radiation oncology peer review have been described. However, despite the importance of peer review in radiation oncology barriers may exist to its effective implementation in practice. The purpose of this study was to quantify the rate of plan changes based on our group peer review process as well as the quantify amount of time and resources needed for this process. METHODS: Data on cases presented in our institutional group consensus peer review conference were prospectively collected. Cases were then retrospectively analyzed to determine the rate of major change (plan rejection) and any change in plans after presentation as well as the median time of presentation. Univariable logistic regression was used to determine factors associated with major change and any change. RESULTS: There were 73 cases reviewed over a period of 11 weeks. The rate of major change was 8.2% and the rate of any change was 23.3%. The majority of plans (53.4%) were presented in 6-10 min. Overall, the mean time of presentation was 8 min. On univariable logistic regression, volumetric modulated arc therapy plans were less likely to undergo a plan change but otherwise there were no factors significantly associated with major plan change or any type of change. CONCLUSION: Group consensus peer review allows for a large amount of informative clinical and technical data to be presented per case prior to the initiation of radiation treatment in a thorough yet efficient manner to ensure plan quality and patient safety.

Reliable Radiation Technique to Minimize Ovarian Dose During Radiation Prophylaxis of Heterotopic Ossification.

BACKGROUND/AIM: Scattered radiation during radiotherapy (RT) directed at the hip joint poses concerns about ovarian function in patients of reproductive age. Here, we report the impact of using a split-beam technique (SBT) and different photon energies on the total ovary dose during radiation prophylaxis of heterotopic ossification (HO). PATIENTS AND METHODS: This was a single-institution, retrospective study of 32-patients with traumatic acetabular fractures (TAF). All underwent surgery followed by CT-based-RT within 72 h in a single fraction of 700 cGy. Ipsilateral (IL) and contralateral (CL) ovaries (OV) were contoured separately and dose volume histograms (DVH) generated. Additional planning trials were created for each patient by utilizing a SBT medially and by using different photon energies (6-18 MV) to investigate the difference in ovary dose among these maneuvers. RESULTS: The median Mean-dose delivered to ILOV was 59 cGy and the median Max-dose was 177 cGy. CLOV median Mean-dose was 6 cGy and median Max-dose was 10 cGy. SBT at the medial edge of the field led to a 27% and 22% dose reduction in the median Mean and Max. doses, respectively, to ILOV; 9% and 5% reduction was seen in the median Mean and Max. doses, respectively, to CLOV. Higher photon energies (10-18 MV) led to an additional 28% and 16 % reduction in median Mean and Max. doses, respectively, to ILOV when compared to those from 6 MV. The CLOV median Mean dose was reduced by 18% and the Max. dose was reduced by 12%. CONCLUSION: A biologically significant radiation dose is delivered to the ovaries during HO radiation prophylaxis at the hip joints. Ipsilateral ovarian dose could be reduced by half and contralateral by one-quarter by using CT-based treatment planning with a medial SBT and photon energies above 6 MV. We suggest using no more than 10 MV to minimize neutron contamination. Those techniques should be the standard of care as it provides a reliable method for minimizing the radiation dose to the ovaries, consequently, maximizing female fertility preservation during HO radiation prophylaxis. All female patients in childbearing age should be fully informed about ovarian radiation exposure and possible temporary alteration in ova production and morphology.

Testicular Dose During Prophylaxis of Heterotopic Ossification with Radiation Therapy.

AIM: A single-institution, retrospective study was performed to investigate potential techniques to minimize radiation exposure to the testicles during heterotopic ossification (HO) prophylaxis. We report the impact of split-beam technique (SBT) and different photon energies on the total dose of radiation received by the testicles during prophylaxis of HO. MATERIALS AND METHODS: Between 2008 and 2010, we identified 64 patients with traumatic acetabular fractures who underwent surgery followed by radiation therapy (RT) without testicular shielding. Postoperative RT was delivered within 72 h in a single fraction of 700 cGy using 6-18 MV photons, without testicular shielding due to patient refusal. All patients underwent 3-D RT planning in which the testicles were contoured as a region of interest and dose-volume histograms (DVH) were generated. Additional treatment planning trials were created for each patient by utilizing a SBT medially and by using different photon energies (6, 10 and 18 MV) to study the effects of these maneuvers on the delivered dose to the testicles. RESULTS: In reviewing the DVH, it was noted that the mean dose delivered to the testicles was 10 cGy (range=3-40). The maximum dose was 31 cGy (range=7-430). When SBT was utilized, a significant reduction in the mean (44%) and maximum (47%) doses delivered to the testicles was noted. Further reductions in the mean (26%) and maximum (14%) doses were achieved by using higher-energy (10-18 MV) beams. The radiation doses to the testicles from the CT simulation and the two portal images were estimated to be 4 and 1.5 cGy, respectively. CONCLUSION: Low-dose prophylactic RT to prevent HO around the hip causes a low, but likely biologically meaningful, radiation dose to be delivered to the testicles. This dose could be further reduced by using a medial SBT and photon energies above 6 MV. Testicular shielding should be offered to all male patients receiving such RT. In addition, all patients should be informed about the consequences of testicular radiation as part of their informed consent.

Dosimetric comparison of brachytherapy sources for high-dose-rate treatment of endometrial cancer: (192)Ir, (60)Co and an electronic brachytherapy source.

OBJECTIVE: To compare high-dose-rate (HDR) brachytherapy systems with (192)Ir, (60)Co and electronic brachytherapy source (EBS) for treatment of endometrial cancers. METHODS: Two additional plans were generated per patient fraction using a (60)Co source and Xoft-EBS on 10 selected patients, previously treated with a vaginal cylinder applicator using a (192)Ir source. Dose coverage of "PTV_CYLD", a 5-mm shell surrounding the cylinder, was evaluated. Doses to the following organs at risk (OARs) the rectum, bladder and sigmoid were evaluated in terms of V35% and V50%, the percentage volume receiving 35% and 50% of the prescription dose, respectively, and D2cm(3), the highest dose to a 2-cm(3) volume of an OAR. RESULTS: Xoft-EBS reduces doses to all OARs in the lower dose range, but it does not always provide better sparing of the rectum in higher dose range as does evaluation using D2cm3. V150% and V200% for PTV_CYLD was up to four times greater for Xoft-EBS plans than for plans generated with (192)Ir or (60)Co. Surface mucosal (vaginal cylinder surface) doses were also 23% higher for Xoft-EBS than for (192)Ir or (60)Co plans. CONCLUSION: Xoft-EBS is a suitable HDR source for vaginal applicator treatment with advantages of reducing radiation exposure to OARs in the lower dose range, while simultaneously increasing the vaginal mucosal dose. ADVANCES IN KNOWLEDGE: This work presents newer knowledge in dosimetric comparison between (192)Ir or (60)Co and Xoft-EBS sources for endometrial vaginal cylinder HDR planning.

Radiation safety consideration during intraoperative radiation therapy.

Using in-house-designed phantoms, the authors evaluated radiation exposure rates in the vicinity of a newly acquired intraoperative radiation therapy (IORT) system: Axxent Electronic Brachytherapy System. The authors also investigated the perimeter radiation levels during three different clinical intraoperative treatments (breast, floor of the mouth and bilateral neck cancer patients). Radiation surveys during treatment delivery indicated that IORT using the surface applicator and IORT using balloons inserted into patient body give rise to exposure rates of 200 mR h(-1), 30 cm from a treated area. To reduce the exposure levels, movable lead shields should be used as they reduce the exposure rates by >95%. The authors' measurements suggest that intraoperative treatment using the 50-kVp X-ray source can be administered in any regular operating room without the need for radiation shielding modification as long as the operators utilise lead aprons and/or stand behind lead shields.

Short-term clinical outcome and dosimetric comparison of tandem and ring versus tandem and ovoids intracavitary applicators.

PURPOSE: To compare the short-term toxicity and dosimetry of tandem and ring (TR), and tandem and ovoid (TO) applicators in treatment of gynecologic malignancy. MATERIAL AND METHODS: Following pelvic external beam radiation therapy (EBRT), a total of 52 computed tomography-based plans from 13 patients with cervical cancer (FIGO IB2-IIIB) were evaluated for HDR brachytherapy. Prescription was 7 Gy to the ICRU point A for four weekly fractions. Gastrointestinal and genitourinary toxicities were evaluated. Clinical target volume (CTV) and organs at risk were delineated on CT scans. Bladder, rectum, and sigmoid mean doses and D2cc were calculated. Treatment time and irradiated tissue volume were compared. Percent of CTV receiving 100% (CTV100%) of the prescribed dose as well as the percent of the prescription dose covering 90% of the CTV (D90) were evaluated. RESULTS: Gastrointestinal and genitourinary toxicities were not different between TO and TR applicators. No significant differences in the dose to the right and left point A, or the left point B were observed. TO delivered a higher dose to right point B. Organs at risk doses were similar between the two applicators, except mean rectal dose was lower for TO applicator. Overall, TO treats a larger tissue volume than TR. Mean treatment time was shorter for TR. Tumor coverage (D90 and CTV100%) was equivalent between TO and TR applicators. CONCLUSION: Although TO treats a larger tissue volume than TR, short-term toxicities and tumor coverage are similar. Long-term clinical outcomes will be elucidated with longer follow up period.

A prolonged time interval between trauma and prophylactic radiation therapy significantly increases the risk of heterotopic ossification.

PURPOSE: To ascertain whether the time from injury to prophylactic radiation therapy (RT) influences the rate of heterotopic ossification (HO) after operative treatment of displaced acetabular fractures. METHODS AND MATERIALS: This is a single-institution, retrospective analysis of patients referred for RT for the prevention of HO. Between January 2000 and January 2009, 585 patients with displaced acetabular fractures were treated surgically followed by RT for HO prevention. We analyzed the effect of time from injury on prevention of HO by RT. In all patients, 700 cGy was prescribed in a single fraction and delivered within 72 hours postsurgery. The patients were stratified into five groups according to time interval (in days) from the date of their accident to the date of RT: Groups A ≤3, B ≤7, C ≤14, D ≤21, and E >21 days. RESULTS: Of the 585 patients with displaced acetabular fractures treated with RT, (18%) 106 patients developed HO within the irradiated field. The risk of HO after RT increased from 10% for RT delivered ≤3 days to 92% for treatment delivered >21 days after the initial injury. Wilcoxon test showed a significant correlation between the risk of HO and the length of time from injury to RT (p < 0.0001). Chi-square test and multiple logistic regression analysis showed no significant association between all other factors and the risk of HO (race, gender, cause and type of fracture, surgical approach, or the use of indomethacin). CONCLUSIONS: Our data suggest that there is higher incidence and risk of HO if prophylactic RT is significantly delayed after a displaced acetabular fracture. Thus, RT should be administered as early as clinically possible after the trauma. Patients undergoing RT >3 weeks from their displaced acetabular fracture should be informed of the higher risk (>90%) of developing HO despite prophylaxis.

Lack of Cetuximab induced skin toxicity in a previously irradiated field: case report and review of the literature.

INTRODUCTION: Mutation, amplification or dysregulation of the EGFR family leads to uncontrolled division and predisposes to cancer. Inhibiting the EGFR represents a form of targeted cancer therapy. CASE REPORT: We report the case of 79 year old gentleman with a history of skin cancer involving the left ear who had radiation and surgical excision. He had presented with recurrent lymph node in the left upper neck. We treated him with radiation therapy concurrently with Cetuximab. He developed a skin rash over the face and neck area two weeks after starting Cetuximab, which however spared the previously irradiated area. CONCLUSION: The etiology underlying the sparing of the previously irradiated skin maybe due to either decrease in the population of EGFR expressing cells or decrease in the EGFR expression. We raised the question that "Is it justifiable to use EGFR inhibitors for patients having recurrence in the previously irradiated field?" We may need further research to answer this question which may guide the physicians in choosing appropriate drug in this scenario.