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Biomedical subjects

S Nag

Publications and source records attributed to S Nag.

At least 37 records · Page 2Linked to original sources

Brachytherapy in the treatment of breast cancer.

Whole-breast external-beam radiation therapy (EBRT) involves a 6-week course of fractionated treatments. In contrast, brachytherapy can be completed in a 4- to 5-day treatment course. Because of this shortened time frame, there has been interest in breast brachytherapy as a sole modality after lumpectomy. The American Brachytherapy Society (ABS) has issued guidelines specifically for the use of brachytherapy in breast carcinoma. In these guidelines, the ABS addresses important areas of controversy related to the indications, execution, and evaluation of breast implants when utilized in the following settings: as the sole treatment modality following lumpectomy, as an alternative to a 6-week course of EBRT following lumpectomy, as a boost following whole-breast irradiation, and for the treatment of local recurrences following breast-conservation treatment. The ABS recommends a precise definition and meticulous delineation of the clinical target volume. In addition, the Society recommends the routine use of dose-volume histograms and a dose-homogeneity index as tools to ensure reproducible brachytherapy and to allow interinstitutional comparisons. Brachytherapy as a sole modality is currently considered investigational and should be performed in the context of a controlled clinical trial. Practitioners and cooperative groups are encouraged to use these guidelines to formulate treatment and dose-reporting policies, but responsibility for medical decisions ultimately rests with the treating radiation oncologist.

Brachytherapy↗

Expression of nitric oxide synthases and nitrotyrosine during blood-brain barrier breakdown and repair after cold injury.

This study was undertaken to determine whether the blood-brain barrier (BBB) breakdown and cerebral edema occurring post-trauma are associated with overexpression of the endothelial (e) and inducible (i) nitric oxide synthases (NOS), enzymes responsible for nitric oxide (NO) biosynthesis. These enzymes were determined quantitatively at the mRNA level and qualitatively at the protein level in the rat cerebral cortical cold injury model, during a period up to 6 days post-injury. In addition, peroxynitrite generation at the lesion site was detected by immunolocalization of nitrotyrosine as a marker of NO-superoxide interactions. These studies were correlated with the permeability status of the BBB by immunohistochemical detection of endogenous fibronectin extravasation in the same brains. BBB breakdown was immediate in lesion vessels, it was present as early as 10 minutes post-lesion and delayed in perilesional vessels that showed maximal BBB breakdown between 2-4 days. The BBB was restored to normal at 6 days post-lesion. An increase in both eNOS and iNOS mRNA was observed at the lesion site as compared with the contralateral hemisphere at 12 hours, 2 days, and 4 days. The mRNA returned to resting levels by 6 days. Increased eNOS protein was observed in the endothelium of permeable perilesional vessels and neovessels and in the endothelium of the hyperplastic pial vessels overlying the lesion site. iNOS protein was observed initially in polymorphonuclear leukocytes at the lesion site and later in macrophages, endothelial cells, and the smooth muscle cells of the overlying pial vessels. Furthermore, nitrotyrosine was demonstrated at the lesion site up to 5 days. Up-regulation of the NO synthases at both the mRNA and protein level accompanied by presence of nitrotyrosine during BBB breakdown and angiogenesis suggests that NO has a role in the pathogenesis of these processes.

Animals↗

Audit of influenza and pneumococcal vaccination uptake in diabetic patients attending secondary care in the Northern Region.

AIMS: To document uptake of influenza and pneumococcal vaccination in diabetic patients attending secondary care in the Northern Region, and to explore influencing factors. METHODS: Diabetic patients attending out-patients in Middlesbrough, Gateshead and Newcastle were questioned from October 1999 to March 2000. Physicians inquired about influenza and pneumococcal vaccination status using a standardized questionnaire. Data collected included age, year of diagnosis, duration of diabetes, type of diabetes, and the presence of other recognized indications for vaccination. RESULTS: Two hundred and sixty-eight diabetic patients, 42% (113/268) with Type 1 diabetes, 34% (91/268) with ischaemic heart disease, 10% (26/268) with chronic pulmonary disease (CPD) and 10% (27/268) with chronic renal disease, were questioned. Thirty-five percent (93/268) of patients received both influenza and pneumococcal vaccines, 24% (64/268) received only influenza vaccine, and none received pneumococcus vaccine alone. Most vaccinees received advice about influenza and pneumococcal vaccination from their general practitioner (90% (142/157) and 87% (81/93), respectively). A large number of non-vaccinees were unaware of the need for influenza and pneumococcal vaccination (69% (76/111) and 91% (159/175), respectively). Using multiple logistic regression co-existing CPD increased the odds of receiving influenza (odds ratio (OR) (95% confidence interval (CI)) = 1.99 (1.07-14.12)) or pneumococcal (OR = 3.77 (1.69-21.76)) vaccination. Furthermore, each 1-year increase in age increased the chance of receiving influenza or pneumococcal vaccination by 22% (OR = 1.22 (1.09-1.67) and 29% (OR = 1.29 (1.07-1.72)), respectively. CONCLUSIONS: Vaccination rates in these diabetic patients are unsatisfactory. Secondary care health professionals might increase rates by raising the topic in consultations. Diabet. Med. 18, 599-603 (2001)

Adolescent↗

Long-term follow-up on an intensified treatment regimen for advanced resectable head and neck squamous cell carcinomas.

From February 1993 through July 1994, 37 patients with stage III-IV squamous cell carcinomas of the oral cavity, oropharynx, or hypopharynx (stage II-IV) were registered to a treatment regimen consisting of preoperative continuous infusion cisplatin (80 mg/m2/80 hours) with hyperfractionated external beam radiotherapy (9.1 Gy/7 fractions of 1.3 Gy BID), surgical resection, intraoperative radiotherapy (7.5 Gy), and postoperative radiotherapy (40 Gy) with concurrent cisplatin (100 mg/m2 x 2 courses). The objectives of the regimen were to improve patient compliance while also increasing treatment intensity. The purpose of this article is to report the local, regional (nodal), and distant disease control of these patients after an extended time at risk (median 40 months). Overall compliance (73%), local control at primary site (97%), and regional nodal control (95%) were excellent. The rate of distant metastasis was 19%. Absolute survival at 48 months was 45.9%.

Carcinoma, Squamous Cell↗

Differential response of sensory and motor axons in nerve allografts after withdrawal of immunosuppressive therapy.

OBJECT: Rejection of nerve allografts and loss of regenerated host axons after withdrawal of immunosuppressive therapy poses an ongoing challenge in peripheral nerve repair. The present report is of a blinded prospective controlled study in which an established rat model of nerve allotransplantation is used to examine the effect of fiber type on survival and degeneration of nerve allografts after discontinuation of immunosuppression. The authors hypothesized that sensory axons will selectively resist a rejection response, whereas motor axons will degenerate. METHODS: Four-centimeter nerve segments from ACI rats were grafted into peroneal and sural (mixed) or saphenous (sensory) nerve gaps in Lewis rats. In some rats, L4-6 dorsal root ganglia were ablated before grafting, creating pure motor sural and peroneal nerves. All rats received 12 weeks of immunosuppressive therapy to support nerve regeneration into allografts. Immunosuppression with cyclosporin was then withdrawn. At planned death (12-18 weeks postsurgery), graft tissue was subjected to histomorphometric analysis for evaluation of axon survival and loss. Graft rejection led to loss of all axons in approximately 60% of the allograft segments. The mixed nerve group was most prone to complete rejection, with significantly lowered axon counts at Weeks 16 and 18 compared with the Week 12 baseline. Axons from the sensory nerve were least likely to degenerate. The pure motor nerve group axons demonstrated intermediate sensitivity, with a selective loss of larger axons at Week 16 and a significant decrease in axon counts from the Week 12 baseline at Week 18. CONCLUSIONS: Whereas the majority of axons are lost after withdrawal of immunosuppressive therapy from nerve allografts, there is a selective survival of axons from cutaneous sensory nerves and smaller-diameter motor fibers. The biological and molecular mechanisms that make some axons impervious to injury remain to be determined.

Animals↗

Glioblastoma multiforme occurring in a patient treated with gamma knife surgery. Case report and review of the literature.

Stereotactic radiosurgery is being increasingly advocated as the primary modality for treatment of vestibular schwannomas (VS). This modality has been shown to arrest tumor growth, with few associated short-term morbidities, and with possibly better hearing and facial nerve preservation rates than microsurgery. Radiation-induced oncogenesis has long been recognized, although stereotactic radiosurgery de novo induction of a secondary tumor has never been clearly described. The authors report on a patient with a VS who did not have neurofibromatosis Type 2 and who underwent gamma knife surgery (GKS). This patient required microsurgical removal of the VS within 8 months because of development of a tumor cyst with associated brainstem compression and progressive hydrocephalus. The operation resulted in clinical stabilization and freedom from tumor recurrence. Seven and a half years after undergoing GKS, the patient presented with symptoms of raised intracranial pressure. Magnetic resonance imaging demonstrated a new ring-enhancing lesion in the inferior temporal lobe adjacent to the area of radiosurgery, which on craniotomy was confirmed to be a glioblastoma multiforme (GBM). Despite additional conventional external-beam radiation to the temporal lobe, the GBM has progressed. Whereas this first reported case of a GBM within the scatter field of GKS does not conclusively prove a direct causal link, it does fulfill all of Cahan's criteria for radiation-induced neoplasia, and demands increased vigilance for the potential long-term complications of stereotactic radiosurgery, and reporting of any similar cases.

Brain Neoplasms↗

Early voiding dysfunction associated with prostate brachytherapy.

Introduction: Transperineal prostate brachytherapy is gaining popularity as a treatment for clinically localized carcinoma of the prostate. Very little prospective data exists addressing the issue of complications associated with this procedure. We present an analysis of the early voiding dysfunction associated with prostate brachytherapy. Materials and Methods: Forty-six consecutive patients who underwent Palladium-103 (Pd-103) seed placement for clinically localized prostate carcinoma were evaluated prospectively for any morbidity associated with the procedure. Twenty-three patients completed an International Prostate Symptom Score (IPSS) questionnaire preoperatively, at their first postoperative visit, and at their second postoperative visit. The total IPSS, each of the seven individual components, and the "bother" score were evaluated separately for each visit, and statistical significance was determined. Results: Urinary retention occurred in 7/46 patients (15%). Of these, 5 were able to void spontaneously after catheter removal. One patient is maintained with a suprapubic tube, and one patient is currently on continuous intermittent catheterization. Baseline IPSS was 7.1 and this went to 20.0 at the first postoperative visit (p<0.001). By the second postoperative visit, the IPSS was 8.0. Conclusions: In our experience, prostate brachytherapy for localized carcinoma of the prostate is associated with a 15% catheterization rate and a significant increase in the IPSS (7.1 to 20.0). This increase in the IPSS seems to be self-limited. Patients need to be educated on these issues prior to prostate brachytherapy.

Journal Article↗

The American Brachytherapy Society recommendations for high-dose-rate brachytherapy for carcinoma of the endometrium.

PURPOSE: To develop recommendations for use of high-dose-rate (HDR) brachytherapy in patients with endometrial cancer. METHODS: A panel of members of the American Brachytherapy Society (ABS) performed a literature review, supplemented their clinical experience, and formulated recommendations for endometrial HDR brachytherapy. RESULTS: The ABS endorses the National Comprehensive Cancer Network (NCCN) guidelines for indications for radiation therapy for patients with endometrial cancer and the guidelines on HDR quality assurance of the American Association on Physicists in Medicine (AAPM). The ABS made specific recommendations for HDR applicator selection, insertion techniques, target volume definition, dose fractionation, and specifications for postoperative adjuvant vaginal cuff therapy, for vaginal recurrences, and for medically inoperable primary endometrial cancer patients. The ABS recommends that applicator selection should be based on patient and target volume geometry. The dose prescription point should be clearly specified. The treatment plan should be optimized to conform to the target volume whenever possible while recognizing the limitations of computer optimization. Suggested doses were tabulated for treatment with HDR alone, and in combination with external beam radiation therapy (EBRT), when applicable. For intravaginal brachytherapy, the largest diameter applicator should be selected to ensure close mucosal apposition. Doses should be reported both at the vaginal surface and at 0.5-cm depth irrespective of the dose prescription point. For vaginal recurrences, intracavitary brachytherapy should be restricted to patients with nonbulky (< 0.5-cm thick) disease. Patients with bulky (> 0.5-cm thick) recurrences should be treated with interstitial techniques. For medically inoperable patients, an appropriate applicator that will allow adequate irradiation of the entire uterus should be selected. CONCLUSION: Recommendations are made for HDR brachytherapy for endometrial cancer. Practitioners and cooperative groups are encouraged to use these recommendations to formulate their treatment and dose reporting policies. This will lead to meaningful comparisons of reports from different institutions and lead to advances and appropriate use of HDR.

Brachytherapy↗

A rapid and sensitive assay method for measuring amine oxidase based on hydrogen peroxide-titanium complex formation.

Hydrogenperoxide (H(2)O(2)) is an end product of diamine and polyamine oxidation by their respective oxidase enzymes. A new sensitive assay method is based on a H(2)O(2)-titanium (Ti) complex formation as an indicator of H(2)O(2) production due to polyamine oxidation. The orange-yellow coloured H(2)O(2)-Ti complex was measured at 410 nm in a Shimadzu spectrophotometer. The assay conditions for maximum diamine oxidase (DAO) and polyamine oxidase (PAO) as standardized here using the hypocotyl tissues of Vigna catjang Endl. cv Pusa Barsati consisted of pH 7.4 (40 mM potassium phosphate buffer), 3 mM substrate (putrescine or spermine), 37 degrees C incubation temperature and 30 min incubation time in the presence of catechol (10(-2) M) used as an inhibitor of both peroxidase and catalase activity. The method described here was significantly more sensitive than the starch-iodide method [T.A. Smith, Biochem. Biophys. Res. Commun. 41 (1970) 1452-1456], which could be improved further if measured under the same assay conditions as described for the H(2)O(2)-Ti method. Sensitivity of the present method was tested by assaying DAO/PAO activity in auxin treated hypocotyls of Vigna and comparing it with the starch-iodide method in two other plant samples.

Journal Article↗

The American Brachytherapy Society recommendations for high-dose-rate brachytherapy for carcinoma of the cervix.

PURPOSE: This report presents guidelines for using high-dose-rate (HDR) brachytherapy in the management of patients with cervical cancer, taking into consideration the current availability of resources in most institutions. METHODS: Members of the American Brachytherapy Society (ABS) with expertise in HDR brachytherapy for cervical cancer performed a literature review, supplemented their clinical experience to formulate guidelines for HDR brachytherapy of cervical cancer. RESULTS: The ABS strongly recommends that definitive irradiation for cervical carcinoma must include brachytherapy as a component. Each institution should follow a consistent treatment policy when performing HDR brachytherapy, including complete documentation of treatment parameters and correlation with clinical outcome, such as pelvic control, survival, and complications. The goals are to treat Point A to at least a total low-dose-rate (LDR) equivalent of 80-85 Gy for early stage disease and 85-90 Gy for advanced stage. The pelvic sidewall dose recommendations are 50-55 Gy for early lesions and 55-65 Gy for advanced ones. The relative doses given by external beam radiation therapy (EBRT) vs. brachytherapy depend upon the initial volume of disease, the ability to displace the bladder and rectum, the degree of tumor regression during pelvic irradiation, and institutional preference. As with LDR brachytherapy, every attempt should be made to keep the bladder and rectal doses below 80 Gy and 75 Gy LDR equivalent doses, respectively. Interstitial brachytherapy should be considered for patients with disease that cannot be optimally encompassed by intracavitary brachytherapy. While recognizing that many efficacious HDR fractionation schedules exist, some suggested dose and fractionation schemes for combining the EBRT with HDR brachytherapy for each stage of disease are presented. These recommendations are intended only as guidelines, and the suggested fractionation schemes have not been thoroughly tested. The responsibility for the medical decisions ultimately rests with the treating radiation oncologist. CONCLUSION: Guidelines are established for HDR brachytherapy for cervical cancer. Practitioners and cooperative groups are encouraged to use these guidelines to formulate their treatment and dose-reporting policies. These guidelines will be modified, as image-based treatment becomes more widely available.

Antineoplastic Agents↗

DNA-cleavage studies on N-substituted monocyclic enediynes: enhancement of potency by incorporation of intercalating or electron poor aromatic ring and subsequent design of a novel phototriggerable acyclic enediyne.

A number of novel N-substituted enediynes (azaenediynes) 1-4 were synthesized as DNA cleaving agents. Enhancement of DNA cleavage potency was observed with those compounds which could interact with DNA through intercalation of the extended aromatic ring or through electrostatic attraction with electron poor aromatic ring. An acyclic enediyne 5 with a novel phototriggerable device was also synthesized and its DNA-cleaving activity was established.

DNA↗

American brachytherapy society recommendations for clinical implementation of NIST-1999 standards for (103)palladium brachytherapy. The clinical research committee of the American Brachytherapy Society.

PURPOSE: Recent important developments in palladium-103 ((103)Pd) dosimetry mandate a reevaluation of (103)Pd brachytherapy prescribing practices. METHODS AND MATERIALS: The clinical research committee of the American Brachytherapy Society (ABS) convened a consensus session of brachytherapists and physicists to develop recommendations regarding future dose prescribing guidelines for National Institute of Standards and Technology (NIST-1999) calibrated (103)Pd sources. RESULTS: The ABS recommends that clinicians attempt to reproduce the implant doses delivered and reported in the literature through the past decade. CONCLUSIONS: The following should be immediately implemented for (103)Pd dosimetry: 1) All practicing physicians, physicists, dosimetrists, and suppliers implement NIST-1999 air-kerma strength standard for (103)Pd brachytherapy. 2) All treatment planning systems and dose calculation algorithms must be updated to reflect new dose rate constants. The AAPM-recommended validated value for Theraseed model 200 is 0.665 cGy h(-1) U(-1). The dose rate constant for the Mentor MED3633 seed is currently reported as 0.68 cGy h(-1) U(-1). This latter value and the values for seeds from other manufacturers are awaiting independent confirmation. 3) Physicians who previously prescribed 115 Gy for (103)Pd monotherapy prostate implants should now prescribe 125 Gy. When using (103)Pd as a boost following 45 Gy of external beam irradiation, 100 Gy should be prescribed instead of the previous 90 Gy. It is critical that all three changes be implemented concurrently, because they are interdependent.

Brachytherapy↗

A simple method of obtaining equivalent doses for use in HDR brachytherapy.

PURPOSE: To develop a simple program that can be easily used by clinicians to calculate the tumor and late tissue equivalent doses (as if given in 2 Gy/day fractions) for different high-dose-rate (HDR) brachytherapy regimens. The program should take into account the normal tissue sparing effect of brachytherapy. METHODS AND MATERIALS: Using Microsoft Excel, a program was developed incorporating the linear-quadratic (LQ) formula to calculate the biologically equivalent dose (BED). To express the BED in terms more familiar to all clinicians, it was reconverted to equivalent doses as if given as fractionated irradiation at 2 Gy/fraction. Since doses given to normal tissues in HDR brachytherapy treatments are different from those given to tumor, a normal tissue dose modifying factor (DMF) was applied in this spreadsheet (depending on the anticipated dose to normal tissue) to obtain more realistic equivalent normal tissue effects. RESULTS: The spreadsheet program created requires the clinician to enter only the external beam total dose and dose/fraction, HDR dose, and the number of HDR fractions. It automatically calculates the equivalent doses for tumor and normal tissue effects, respectively. Generally, the DMF applied is < 1 since the doses to normal tissues are less than the doses to the tumor. However, in certain circumstances, a DMF of > 1 may need to be applied if the dose to critical normal tissues is higher than the dose to tumor. Additionally, the alpha/beta ratios for tumor and normal tissues can be changed from their default values of 10 Gy and 3 Gy, respectively. This program has been used to determine HDR doses needed for treatment of cancers of the cervix, prostate, and other organs. It can also been used to predict the late normal tissue effects, alerting the clinician to the possibility of undue morbidity of a new HDR regimen. CONCLUSION: A simple Excel spreadsheet program has been developed to assist clinicians to easily calculate equivalent doses to be used in HDR brachytherapy regimens. The novelty of this program is that the equivalent doses are expressed as if given at 2 Gy per fraction rather than as BED values and a more realistic equivalent normal tissue effect is obtained by applying a DMF. Its ease of use should promote the use of LQ radiobiological modeling to determine doses to be used for HDR brachytherapy. The program is to be used judiciously as a guide only and should be correlated with clinical outcome.

Algorithms↗

The American Brachytherapy Society recommendations for permanent prostate brachytherapy postimplant dosimetric analysis.

PURPOSE: The purpose of this report is to establish guidelines for postimplant dosimetric analysis of permanent prostate brachytherapy. METHODS: Members of the American Brachytherapy Society (ABS) with expertise in prostate dosimetry evaluation performed a literature review and supplemented with their clinical experience formulated guidelines for performing and analyzing postimplant dosimetry of permanent prostate brachytherapy. RESULTS: The ABS recommends that postimplant dosimetry should be performed on all patients undergoing permanent prostate brachytherapy for optimal patient care. At present, computed tomography (CT)-based dosimetry is recommended, based on availability cost and the ability to image the prostate as well as the seeds. Additional plane radiographs should be obtained to verify the seed count. Until the ideal postoperative interval for CT scanning has been determined, each center should perform dosimetric evaluation of prostate implants at a consistent postoperative interval. This interval should be reported. Isodose displays should be obtained at 50%, 80%, 90%, 100%, 150%, and 200% of the prescription dose and displayed on multiple cross-sectional images of the prostate. A dose-volume histogram (DVH) of the prostate should be performed and the D90 (dose to 90% of the prostate gland) reported by all centers. Additionally, the D80, D100, the fractional V80, V90, V100, V150 and V200 (i.e., the percentage of prostate volume receiving 80%, 90%, 100%, 150%, and 200% of the prescribed dose, respectively), the rectal, and urethral doses should be reported and ultimately correlated with clinical outcome in the research environment. On-line real-time dosimetry, the effects of dose heterogeneity, and the effects of tissue heterogeneity need further investigation. CONCLUSION: It is essential that postimplant dosimetry should be performed on all patients undergoing permanent prostate brachytherapy. Guidelines were established for the performance and analysis of such dosimetry.

Brachytherapy↗

Increased immunolocalization of nitric oxide synthases during blood-brain barrier breakdown and cerebral edema.

The role of nitric oxide (NO) in blood-brain barrier (BBB) breakdown and edema formation was investigated in the rat cortical cold injury model over a period of 10 min to 6 days post cold-injury by immunolocalization of fibronectin as a marker of BBB permeability alterations and endothelial (e) and inducible (i) nitric oxide synthases (NOS), which are markers of NO biosynthetic activity. BBB breakdown to fibronectin in lesion vessels was observed at 10 minutes post-injury, was maximal between 60 minutes and 3 hours and declined gradually thereafter, while perilesional vessels remained permeable up to 5 days. Increased eNOS immunoreactivity was observed in endothelium of perilesional permeable vessels starting at 12 hrs and was maximal between 4-6 days, after which immunoreactivity decreased reaching basal levels by 5-6 days. Immunoreactivity for iNOS was absent in normal brain and was first observed in polymorphonuclear leukocytes and endothelium of lesion vessels at 3 hrs. Maximal iNOS immunoreactivity was observed in endothelial cells and macrophages during the period of angiogenesis. Smooth muscle cells of overlying hyperplastic pial vessels showed iNOS immunoreactivity up to 6 days. The demonstration of increased NO synthases at the lesion site during BBB breakdown and edema formation and angiogenesis suggests that NO plays a role in these processes.

Animals↗

Brain necrosis after permanent low-activity iodine-125 implants: case report and review of toxicity from focal radiation.

Focal irradiation has emerged as a useful modality in the management of malignant brain tumors. Its main limitation is radiation necrosis. We report on the radiation dose distribution in the cerebellum of a patient who developed imaging and autopsy diagnosis of radiation necrosis after permanent iodine-125 implants for a solitary osseous plasmacytoma of her left occipital condyle. A 55-year-old woman initially presented with neck and occipital pain and a lytic lesion of her left occipital condyle. A cytological diagnosis of solitary osseous plasmacytoma was made by transpharyngeal needle biopsy. After an initial course of external beam radiation, the patient required further treatment with systemic chemotherapy 21 months later for clinical and radiographic progression of her disease. She ultimately required subtotal surgical resection of an anaplastic plasmacytoma with intracranial extension. Permanent low-activity iodine-125 seeds were implanted in the tumor cavity. Satisfactory local control was achieved. However, clinical and imaging signs of radiation damage appeared 28 months after iodine-125 seed implantation. Progressive systemic myeloma led to her death 11 years after presentation and 9 years after seed implantation. Radiation dose distribution is described, with a discussion of toxicity from focal radiation dose escalation.

Algorithms↗