May Abdel-Wahab

Status of radiotherapy resources in Africa: an International Atomic Energy Agency analysis

Radiation therapy is an important component of cancer control programmes. The scarcity of radiation oncology resources in Africa is becoming more severe as cancer incidence increases in the continent. We did a longitudinal assessment of the status of radiation oncology resources in Africa to measure the extent of the problem and the effects of programmes designed to enhance radiation services in the continent. Radiation oncology departments in Africa were surveyed through the Directory of Radiotherapy Centres, and this information was supplemented by that available from International Atomic Energy Agency Regional African and Interregional project reports for 2010. Of 52 African countries included, only 23 are known to have teletherapy. These facilities are concentrated in the southern and northern states of the continent. Brachytherapy resources (high-dose rate or low-dose rate) were only available in 20 of the 52 African countries. Although progress has been made in the establishment of radiation oncology services in some countries, a large need still exists for basic radiation services, and much resource mobilisation is needed for services to keep pace with the burgeoning populations of many countries.

SECOND PRIMARY CANCER AFTER RADIOTHERAPY FOR PROSTATE CANCER : A SEER ANALYSIS OF BRACHYTHERAPY VERSUS EXTERNAL BEAM RADIOTHERAPY

PURPOSE To determine the incidence of second primary cancers (SPCs) and radiotherapy-induced SPCs (RTSPCs). PATIENTS AND METHODS The incidence of SPCs and RTSPCs was compared among four treatment groups with locoregional prostate adenocarcinoma in the 1973-2002 Surveillance, Epidemiology, and End Results database. These groups were no radiotherapy (RT), no surgery (Group 1); external beam RT (EBRT) (Group 2); brachytherapy (Group 3); and a combination of EBRT and brachytherapy (Group 4). RESULTS The age-adjusted estimates of SPCs were greater with EBRT than with brachytherapy (2,178 vs. 1,901 SPCs/100,000; p = 0.025) or with the no RT, no surgery group (1,971 SPCs/100,000; p <0.0001). The age-adjusted rate of late SPC (>or=5 years) for EBRT (2,425 SPCs/100,000) was only significantly greater (p <0.0001) than that for no RT, no surgery (1,950 SPCs/100,000). The hazard ratio adjusted for age, race/ethnicity, and grade was constant at 1.263 for EBRT compared with no RT, no surgery (p <0.0001) but varied with the length of follow-up in both the brachytherapy (0.721 at 5 years to 1.200 at 9 years) and combination (0.920 at 5 years to 1.317 at 9 years) groups. The incidence of RTSPCs was only significantly different between the no RT, no surgery group and the EBRT group, with an increase of 162 cases/100,000 or a 0.16% increased SPC risk (p = 0.023). No significant differences in the incidence of RTSPC were seen between the RT groups. CONCLUSION No significant differences were seen in the incidence of RTSPCs between the RT groups. The initial smaller relative risk of overall SPCs in the brachytherapy group increased with time until the curves converged, suggesting that the effect had resulted from patient selection bias.

Small Cell Carcinoma of the Head and Neck: The University of Miami Experience

PURPOSE To describe the University of Miami experience in the treatment of small cell carcinoma of the head and neck. METHODS AND MATERIALS A total of 12 patients with nonmetastatic small cell carcinoma of the head and neck were treated between April 1987 and September 2007. Radiotherapy was the primary local treatment modality for 8 patients. RESULTS Of the 12 patients, 8 had died after a median follow-up of 13 months. The 4 patients who were alive were followed for a median of 14 months. The Kaplan-Meier estimate of the proportion of small cell head-and-neck cancer patients surviving to 1 and 2 years was 63% and 26%, respectively. The percentage of patients remaining disease free at 1 and 2 years was 71% and 44%, respectively. The patients with tonsil/parotid gland cancer had significantly greater disease-specific survival compared with the other patients. The median survival time was 30 months in the tonsil/parotid group compared with 15.2 months in the other group (patients with small cell carcinoma of the sinonasal cavity, nasopharynx, and larynx). A total of 4 patients developed recurrence, 3 of whom had a distant failure component. The treatment modality was not associated with a difference in disease-specific survival. The 1-year disease-specific survival rate was 73% in the radiotherapy or radiotherapy/chemotherapy group compared with 67% in the other group. CONCLUSION Radiotherapy with or without chemotherapy is a reasonable alternative to surgery for patients with small cell carcinoma of the head and neck. Patients with tonsillar or parotid small cell carcinomas did better than other sites. More aggressive treatment might be warranted for patients with sinonasal carcinoma. The outcome, however, continues to be suboptimal, and more effective therapy is needed because most patients had a component of local and distant failure.

Cobalt, Linac, or Other: What Is the Best Solution for Radiation Therapy in Developing Countries?

The international growth of cancer and lack of available treatment is en route to become a global crisis. With >60% of cancer patients needing radiation therapy at some point during their treatment course, the lack of available facilities and treatment programs worldwide is extremely problematic. The number of deaths from treatable cancers is projected to increase to 11.5 million deaths in 2030 because the international population is aging and growing. In this review, we present how best to answer the need for radiation therapy facilities from a technical standpoint. Specifically, we examine whether cobalt teletherapy machines or megavoltage linear accelerator machines are best equipped to handle the multitudes in need of radiation therapy treatment in the developing world.

The role of hyperfractionated re-irradiation in metastatic brain disease: A single institutional trial

Progression of brain metastases after brain irradiation has prompted several studies on retreatment of the brain. Increased durations of survival and improved quality of life have been reported. Fifteen patients with previously treated brain metastases were entered into this pilot study between May 1990 and January 1994. All patients had neurologic and/or radiologic evidence of progression of brain metastases. The lung was the primary site in 60% of cases. The remaining 40% had breast, ovarian, and skin primaries. The median interval between the first treatment and retreatment was 10 months. All patients received whole-brain irradiation with or without a boost for their initial treatment course. Doses ranged from 3,000 to 5,500 cGy for initial treatments (median, 3,000). Retreatment consisted of limited fields with a median side equivalent square of 8.8 cm. Patients were retreated with a median dose of 3,000 cGy (range, 600-3,000 cGy). A median cumulative dose of 6,000 cGy was achieved. Retreatment consisted of twice-daily fractions (150 cGy/fraction). Retreatment was tolerated without serious complications. Of the 15 patients treated, nine (60%) experienced improvement, and five (27%) had stabilization of neurologic function and/or radiographic parameters. Median survival was 3.2 months; two of the reirradiated patients survived > or = 9 months. In conclusion, reirradiation is a viable option in patients with recurrent metastatic lesions of the brain, and the use of a limited retreatment volume makes this a well-tolerated, low-morbidity treatment that leads to clinical benefits and, in some instances, enhanced survival. The influence of hyperfractionation on the outcome needs to be investigated further in large series.

High-dose-rate remote afterloading intracavitary brachytherapy for the treatment of extrahepatic biliary duct carcinoma.

PURPOSEThe purpose of this study was to determine whether a dose response exists for extrahepatic bile duct carcinoma (EBDC) when treated with increasingly higher radiation doses delivered via a combination of external beam radiation (EBRT) and high dose rate intracavitary brachytherapy (HDRIB). To establish the best tolerated dose of HDRIB. METHODS AND MATERIALSEighteen patients with pathologically proven, locoregional but unresectable or incompletely resected EBDC were studied from 1991–1998 in this phase I/II trial. All patients received EBRT, delivered via megavoltage photons at standard fractionation schedules, for a total dose of 45 Gy. The HDRIB was delivered using the nucleotron HDR remote afterloading unit with a 10 Ci Ir192 source. Each treatment of HDRIB delivered 7 Gy at 1 cm depth. The first group of eight patients received one treatment of HDRIB (Group 1, total dose = 52 Gy). The second group of six patients received two weekly treatments (Group 2, total dose = 59 Gy). The last group of four patients received three weekly treatments of HDRIB (Group 3, total dose = 66 Gy). HDRIB was delivered once weekly concomitant with the EBRT. Acute adverse reactions were evaluated after for each group of patients before escalating to the next higher dose level of HDRIB. RESULTSThe median follow up time for all 18 patients was 15 months. The median survival for all 18 patients was 12.2 months (range 2 to 79.6 months). Overall two-year survival was 27.8%. Three patients (16.7%) had survival of more than 5 years. Dose response is suggested by the median survival of the three groups (9, 12.2, and 20.3 months for Group 1, 2, and 3, respectively), although this did not reach statistical significance. Complete or partial response (>50% reduction in tumor size) was seen in 25% of patients receiving total of 52 Gy compared to 80% of patients (5 patients in Group 2 and 3 patients in Group 3) receiving greater than 59 Gy (P = 0.05). No patients developed Grade 4 complications. One patient in Group 2 developed Grade 3 toxicity after second treatment of HDRIB. CONCLUSIONHigh dose rate brachytherapy of 21 Gy in three divided weekly treatments, plus 45 Gy of external beam radiation is well tolerated. A dose response is shown with significant increase of PR and CR rate for dose >59 Gy. This modality of treatment appears to be safe and effective for inoperable extrahepatic biliary duct carcinoma.

Prognostic factors and survival in patients with spinal cord gliomas after radiation therapy.

The purpose of this study was to determine the impact of various prognostic factors on survival in spinal cord gliomas treated with radiation. Fifty-three patients with spinal cord gliomas irradiated at three major institutions were studied. Fifty-one patients were classified as having ependymoma, astrocytoma, or both. Two patients were classified as having gliomas (otherwise unspecified). Eleven patients had complete resection of their tumor. Biopsy or partial resection was done in the remaining patients. All patients received external beam radiation. Information on these patients was placed in a central database file and analyzed for the effect of several prognostic factors on survival. Overall survival of the entire group was 76.9% and 61.5% at 5 and 10 years, respectively. Pathologic status significantly affected survival (p = 0.03). Patients with ependymomas had a 5-year survival of 93.8% and a 10-year survival of 67.5%. Patients with astrocytoma had a 5-year survival of 64.2% and a 10-year survival of 54%. Univariate analysis showed pathology and the presence of cysts (p = 0.038) to significantly affect survival. Age, sex, location of the primary, extent of surgery radiation dose, and number of involved segments did not affect survival. On multivariate analysis, astrocytic pathology, involvement of more than five segments, male sex, and the absence of cysts (in or adjacent to the tumor) were associated with a significantly inferior survival. This study confirms the importance of pathology and number of segments involved in determining outcome or survival. The presence of cysts adjacent to or within the tumor was found to be associated with an improvement in survival.

Safety in radiation oncology: the role of international initiatives by the International Atomic Energy Agency.

The International Atomic Energy Agency (IAEA) has a wide range of initiatives that address the issue of safety. Quality assurance initiatives and comprehensive audits of radiotherapy services, such as the Quality Assurance Team for Radiation Oncology, are available through the IAEA. Furthermore, the experience of the IAEA in thermoluminescence dosimetric audits has been transferred to the national level in various countries and has contributed to improvements in the quality and safety of radiotherapy. The IAEA is also involved in the development of a safety reporting and analysis system (Safety in Radiation Oncology). In addition, IAEA publications describe and analyze factors contributing to safety-related incidents around the world. The lack of sufficient trained, qualified staff members is addressed through IAEA programs. Initiatives include national, regional, and interregional technical cooperation projects, educational workshops, and fellowship training for radiation oncology professionals, as well as technical assistance in developing and initiating local radiation therapy, safety education, and training programs. The agency is also active in developing staffing guidelines and encourages advanced planning at a national level, aided by information collection systems such as the Directory of Radiotherapy Centers and technical cooperation project personnel planning, to prevent shortages of staff. The IAEA also promotes the safe procurement of equipment for radiation therapy centers within a comprehensive technical cooperation program that includes clinical, medical physics, and radiation safety aspects and review of local infrastructure (room layout, shielding, utilities, and radiation safety), the availability of qualified staff members (radiation oncologists, medical physicists, and radiation technologists and therapists), as well as relevant imaging, treatment planning, dosimetry, and quality control items. The IAEA has taken the lead in developing a comprehensive program that addresses all of these areas of concern and is actively contributing to the national and international efforts to make radiation therapy safer in all settings, including resource-limited settings.

Quality-of-life assessment after hyperfractionated radiation therapy and 5-fluorouracil, cisplatin, and paclitaxel (Taxol) in inoperable and/or unresectable head and neck squamous cell carcinoma

Purpose:To determine quality of life (QOL) after hyperfractionated radiation and chemotherapy. Materials and Methods:Functional Assessment of Cancer Therapy (FACT) and the Functional Assessment of Cancer Therapy–Head and Neck (FACT H-N) questionnaires were administered to protocol patients at baseline study entry, during and at the completion of therapy, and during subsequent follow-up. Results:Twenty-four patients completed baseline QOL questionnaires. Six subsequent assessments were given to patients who were available for follow-up. Social/family well-being and relationship with doctor subscores were not significantly different from baseline. Emotional well-being was not different from baseline initially, but actually showed a significant increase 6 months after completion of radiation, seen on assessments 5 and 6 (P < 0.01). Physical and functional well-being subscores, total FACT-G score, head and neck subscores, and total FACT H-N score all showed initial decreases during, at the completion of radiation, or, in some subscores, up to 3 months postradiation. However, all these scores recovered to baseline levels. These scores subsequently showed a significant increase after 6 months to 1 year in all but the physical well-being and head and neck subscores, which remained at baseline. Conclusion:QOL scores returned to baseline levels or increased at 6 to 12 months postradiation in long-term survivors who completed QOL questionnaires.

Influence of number of CAG repeats on local control in the RTOG 86-10 protocol.

Objectives:The number of CAG repeats on the androgen receptor (AR) gene is inversely proportional to transcriptional activity. The purpose of this study was to determine if short-term androgen deprivation therapy (RT + HT) can improve outcome in patients with tumors with short CAG repeats (<19). Materials and Methods:Prostate cancer patients were randomized to receive either radiotherapy (RT) alone or (RT + HT) in the RTOG 86-10 study. CAG repeats were measured in 94 tumor specimens (21%; test cohort) of the 456 (parent cohort) analyzable cases. AR flow cytometry measurements were done on 13 patients. The effect on local failure (LF), distant metastases (DM), prostate cancer survival (PSS), and overall survival (OS) was studied. Results:Pretreatment characteristics and assigned treatment arm were not significantly different between the parent and test groups except for a significantly higher risk of death (P = 0.049) in the test group. The median CAG repeat was 19. There were no significant differences in stage, or Gleason score between high (19 or greater) and low CAG (<19) patients within each treatment group. Number of CAG repeats alone did not significantly influence LF, DM, PSS, and OS. However, when the CAG repeat outcome was studied in conjunction with androgen deprivation therapy, patients with CAG <19 who received H + RT had improved local control as compared with patients who received RT alone (P = 0.026, 5-year rates 4.6% versus 36.4%) and improved local control over patients with CAG ≥19 that received H + RT (P = 0.028). Conclusions:Patients with short CAG repeats show a local control benefit with short-term androgen deprivation therapy, but no improvement in survival.