Conventional radiotherapy for cervical cancer relies on clinical examination, 3-dimensional conformal radiotherapy (3D-CRT), and 2-dimensional intracavitary brachytherapy. Excellent local control and survival have been obtained for small early stage cervical cancer with definitive radiotherapy. For bulky and locally advanced disease, the addition of chemotherapy has improved the prognosis but toxicity remains significant. New imaging technology such as positron-emission tomography and magnetic resonance imaging has improved tumor delineation for radiotherapy planning. Image-guided radiotherapy (IGRT) may decrease treatment toxicity of whole pelvic radiation because of its potential for bone marrow, bowel, and bladder sparring. Tumor shrinkage during whole pelvic IGRT may optimize image-guided brachytherapy (IGBT), allowing for better local control and reduced toxicity for patients with cervical cancer. IGRT and IGBT should be integrated in future prospective studies for cervical cancer.
Patients with left-sided breast cancer are at risk of cardiac toxicity because of cardiac irradiation during radiotherapy with the conventional 3-dimensional conformal radiotherapy technique. In addition, many patients may receive chemotherapy prior to radiation, which may damage the myocardium and may increase the potential for late cardiac complications. New radiotherapy techniques such as intensity-modulated radiotherapy (IMRT) may decrease the risk of cardiac toxicity because of the steep dose gradient limiting the volume of the heart irradiated to a high dose. Image-guided radiotherapy (IGRT) is a new technique of IMRT delivery with daily imaging, which may further reduce excessive cardiac irradiation. Preliminary results of IGRT for cardiac sparing in patients with left-sided breast cancer are promising and need to be investigated in future prospective clinical studies.
Patients with early stage high-risk prostate cancer (prostate specific antigen > 20, Gleason score > 7) are at high risk of recurrence following prostate cancer irradiation. Radiation dose escalation to the prostate may improve biochemical-free survival for these patients. However, high rectal and bladder dose with conventional three-dimensional conformal radiotherapy may lead to excessive gastrointestinal and genitourinary toxicity. Image-guided radiotherapy (IGRT), by virtue of combining the steep dose gradient of intensity-modulated radiotherapy and daily pretreatment imaging, may allow for radiation dose escalation and decreased treatment morbidity. Reduced treatment time is feasible with hypo-fractionated IGRT and it may improve patient quality of life.
Phytohemagglutinin (PHA) and concanavalin A (Con A) were used as probes to detect changes in the cell surface of Dalton's lymphoma, sarcoma-180 and Ehrlich's carcinoma after short in vitro exposure to acriflavine. Dye-treated cells showed enhancement of agglutination both by PHA and Con A, and such enhancement was found to be dependent on the time of exposure and concentration of acriflavine. However, PHA-induced percent agglutination seemed to be much higher than that of Con A among the 3 cell types. There were also marked differences among the 3 cell types in order of their sensitivity to lectin-mediated agglutination. The strength of the response was greater in lymphoma to both PHA and Con A than that of sarcoma-180 and carcinoma cells, which appeared to be most resistant. Acriflavine, which is known as an intercalative agent with DNA, induces cell surface changes by promoting lectin-mediated cellular agglutination.
The standard of care for metastatic disease is systemic therapy. A unique subset of patients with limited metastatic disease defined as distant involvement of five anatomic sites or less (oligometastases) have a better chance of remission or improved survival and may benefit from local treatments such as surgery or stereotactic body radiotherapy (SBRT). However, to prevent further spread of disease, systemic treatment such as chemotherapy, targeted therapy, and hormonal therapy may be required. Older patients (70 years old or above) or physiologically frail younger patients with multiple co-morbidities may not be able to tolerate the conventional chemotherapy due to its toxicity. In addition, those with a good performance status may not receive optimal chemotherapy due to concern about toxicity. Recently, immunotherapy with checkpoint inhibitors (CPI) has become a promising approach only in the management of program death ligand 1 (PD-L1)-positive tumors. Thus, a treatment method that elicits induction of PD-L1 production by tumor cells may allow all patients with oligometastases to benefit from immunotherapy. In vitro studies have demonstrated that high dose of radiotherapy may induce formation of PD-L1 in various tumors as a defense mechanism against inflammatory T cells. Clinical studies also corroborated those observations. Thus, SBRT, with its high precision to minimize damage to normal organs, may be a potential treatment of choice for older patients with oligometastases due to its synergy with immunotherapy. We propose a protocol combining SBRT to achieve a minimum radiobiologic equivalent dose around 59.5 Gy to all tumor sites if feasible, followed four to six weeks later by CPI for those cancer patients with oligometastases. All patients will be screened with frailty screening questionnaires to identify individuals at high risk for toxicity. The patients will be managed with an interdisciplinary team which includes oncologists, geriatricians, nurses, nutritionists, patient navigators, and social workers to manage all aspects of geriatric patient care. The use of telemedicine by the team may facilitate patient monitoring during treatment and follow-up. Preliminary data on toxicity, local control, survival, and progression-free survival may be obtained and serve as a template for future prospective studies.
Purpose: The objective of this study is to compare dosimetric characteristics of prostate treatments using HDR brachytherapy and IMRT technique. Method and Materials: Five HDR patients were selected for IMRT planning. Patients underwent ultrasound guided catheter placement for HDR. CT images were obtained and imported into the Nucletron PLATO Brachytherapy system. The prostate, urethra, bladder and rectum were contoured on axial slices. The dose was calculated and optimized by graphical optimization. The CT images of these structures were exported from the PLATO to Eclipse workstation for IMRT planning and comparison. For each patient, the DVH of HDR and IMRT plans were generated, drawn on the same scale and compared. Results: In IMRT plans the DVH curves for PTV dropped sharply and reached to zero volume of the prostate at about 6.4 Gy. In HDR plans the DVH curves for PTV showed a long tail up to a very high dose. About 10% of the PTV for prostate received greater than 12 Gy (200%) of the prescribed dose (6 Gy) in HDR plans. In contrast, the same volume in IMRT plans received less than 6 Gy (100%). Average prostate V90 and V100 dose was about 6.3 Gy and 4.12 Gy respectively for HDR, and 6.09 Gy and 5.74 Gy for IMRT plans, respectively. UrethraV90 dose for IMRT plans showed similar levels (93%), whereas in HDR the dose varied widely (60 to 100%). In all plans, the dose to the bladder and rectum was significantly lower in HDR than in IMRT plans. Conclusions: HDR brachytherapy may reduce normal tissue toxicities in prostate boost treatments, even though the dose homogeneity inside the PTV is far worse than in IMRT treatments. Another advantage of HDR over IMRT is that the organ motion is not a significant concern as in IMRT.
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