[Radiotherapy--nonsurgical oncology--development, organization model and need in Norway, Medical oncology with radiotherapy. Development of the field in Norway].
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Humans↗
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[The effect of radiotherapy for glioblastoma: a review of 516 cases (author's transl)].
516 cases of supratentorial glioblastoma, treated in the Department of Surgical Neurology, University of Edinburgh from 1950 through 1970, were analysed with a particular attention to the effect of radiotherapy and the factors contributing to better prognosis. The length of postoperative survival was known in 349 cases and it was more than one month in 238 cases. A megavoltage linear accelerator was introduced in 1955 for radiotherapy of glioblastoma and steroids were started to be used almost routinely in 1966 for pre- and postoperative peritumoral cerebral edema. The policies of the treatment of glioblastoma in this series were; 1) to establish the histological diagnosis and 2) to prolong "useful" postoperative survival of the patient. Among the 516 cases, 271 cases (52.5%) were treated by biopsy alone. More radical procedures and/or radiotherapy were indicated only when survival of the patient was expected to be "useful" for himself and his family. "Useful" life was defined as the condition where the patient was conscious and orientated, and would, on the whole, be glad that he was still alive. Patients with disturbed consciousness, profound aphasia, bedridden or mentally disorganized, were regarded as having useless life. Radiotherapy, if indicated, was given by a 4-megavoltage linear accelerator to the whole brain with a total dose of 4500 rads in a period of 4 weeks. In order to evaluate the effect of radiotherapy, 238 cases who survived more than one month postoperatively were selected, because it took at least one month to complete the course of radiotherapy, because most cases with a biopsy alone survived less than one month, and because unexpected early death due to postoperative complications occurred in one month. The average survival for the irradiated 138 cases was 13.8 months, as compared to 5.2 months for the non-irradiated 100 cases. This difference of 8.6 months was highly significant as confirmed statistically by U-test. Although patients with profound aphasia or severe dimentia were not irradiated, aphasia and dimentia would not affect the length of biological survival of the patient. Therefore, the difference of 8.6 months could be considered as the biological effect of radiotherapy. Among the factors considered, young age, early epilepsy and relatively benign histology (astrocytoma, grade 3) appeared to be related to better prognosis. There was no evidence that a macroscopic circumscribed appearance would contribute to better prognosis. In conclusion, radiotherapy should be indicated for the cases whose survival is expected to be "useful", although its effect is limited.
Adolescent↗
Association of Therapeutic Mammoplasty and Radiotherapy Side-effects.
INTRODUCTION: Patients with larger breast size and volume are at increased risk of side-effects (toxicity) from radiotherapy. Therapeutic mammoplasty (TM) extends breast-conserving surgery by combining wide local excision of the cancer with breast reduction and mastopexy techniques. The aim of this study was to determine the effect of TM using level 2 oncoplastic techniques on the incidence of early and long-term radiotherapy side-effects. PATIENTS AND METHODS: Breast cancer patients recruited prospectively into the multicenter REQUITE cohort study (www.requite.eu) at a single institution (n = 346) were included. Radiotherapy side-effects (CTCAE v4.0) were scored at baseline, following radiotherapy, and at 2-year follow-up. The association of TM and specimen resection weight were investigated in multivariable regression models. RESULTS: At 2 years, 20.1 % of patients had grade ≥ 2 atrophy, 23.2% grade ≥ 1 tumor bed induration (fibrosis), 12.6% grade ≥ 1 breast induration, and 12.1% grade ≥ 1 telangiectasia. 22.5 % of patients (n = 78) underwent TM. TM patients had larger tumors (P = .006) and specimen resection weights (P < .001). TM but not specimen resection weight was associated with reduced tumor bed induration (Odds ratio = 0.12, 95% confidence interval [CI] 0.035-0.395, P = .001), breast induration (OR 0.19, CI 0.043-0.852, P = .03) and telangiectasia (OR 0.12, CI 0.020-0.736, P = .02). Neither TM nor specimen weight had any effect on atrophy or early radiotherapy side-effects. CONCLUSION: TM but not resected specimen weight was associated with fewer long-term radiotherapy side-effects. This implies that the incidence of side-effects is affected not by reducing the overall radiotherapy target volume but by re-shaping the breast, which is likely to reduce dose inhomogeneity.
Humans↗
Screening and identification of key genes related to the immune microenvironment of rectal cancer influenced by radiotherapy based on bioinformatics methods.
OBJECTIVE: Radiotherapy (RT) plays a crucial role in the comprehensive treatment of rectal cancer. However, the impact of radiotherapy on the tumor microenvironment (TME), especially its effect on immune cell infiltration and immune-related gene expression, has not been fully studied. This study aims to screen and analyze key genes related to the immune microenvironment of rectal cancer influenced by radiotherapy based on bioinformatics methods for the purpose of identifying potential biomarkers and providing new insights for the personalized therapy of rectal cancer. METHODS: Using data from the Public Gene Expression Database (GEO) and the Cancer Genomics Database (TCGA), the impact of radiotherapy on the immune microenvironment of rectal cancer was explored using bioinformatics tools. Through screening differentially expressed genes (DEGs), correlation analysis, TIMER database analysis, immune infiltration score, and correlation analysis between key genes and prognosis, the effects of radiotherapy on the immune microenvironment of rectal cancer were investigated. RESULTS: Totally 7 upregulated and 4 downregulated differentially expressed genes were identified, among which MASP1, LTK, SLC9A3R2 were negatively correlated with myeloid suppressor cell infiltration (MDSCs), while ZP2 was positively correlated. The expression of MASP1 and SLC9A3R2 was closely related to the level of immune cell infiltration and played significant roles in the immune microenvironment. High expression of MASP1 was significantly correlated with survival benefits from immune checkpoint inhibitor therapy, while SLC9A3R2 was closely related to the efficacy of PD-L1 inhibitors and CTLA4 inhibitors. CONCLUSIONS: MASP1 and SLC9A3R2, as two key genes that may be related to the immune microenvironment of rectal cancer radiotherapy, deserve further exploration of their roles in the mechanism. The combination of radiotherapy and immunotherapy holds promising prospects in the treatment of rectal cancer, and exploration of related mechanisms will provide new strategies and targets for the treatment of various tumors and rectal cancer.
Bioinformatics↗
Tumor Loss of the Y Chromosome Defines a Biological Phenotype Associated with Resistance to Radiotherapy Across Cancer Types.
PURPOSE: Sex-linked determinants of radiotherapy response remain poorly understood. We investigated whether tumor loss of the Y chromosome (LOY) is associated with biological and clinical features of radiotherapy resistance across cancer types. MATERIALS AND METHODS: We integrated publicly available cancer cell-line experimental datasets and clinical data to evaluate the impact of LOY on radiotherapy response. The radiosensitivity of 125 cancer cell lines, stratified by Y chromosome status, was analyzed. Gene expression analyses were performed to identify biological pathways associated with LOY. Clinical associations were examined in 537 male patients treated with radiotherapy across multiple tumor types in The Cancer Genome Atlas. RESULTS: LOY was associated with increased post-radiotherapy survival in cancer cell lines (p < 0.001). Transcriptomic analyses demonstrated LOY-associated alterations in DNA damage response, senescence, longevity, and proliferation pathways. In TCGA tumors, LOY was associated with remodeling of the tumor microenvironment, including altered immune and stromal signatures. Clinically, LOY was associated with inferior survival in common-support overlap-weighted analyses adjusted for age, tumor stage, and TCGA-defined tumor type. CONCLUSION: These findings suggest that tumor LOY is associated with a distinct biological profile characterized by features of radioresistance and adverse clinical outcomes following radiotherapy. Further studies are warranted to determine whether LOY represents a clinically relevant sex-linked determinant of radiotherapy response.
loss of Y chromosome↗
High-dose radiotherapy in patients with high-risk prostate cancers treated with long-term androgen deprivation therapy (GETUG AFU 18): a randomised, phase 3 trial.
BACKGROUND: For patients with high-risk prostate cancer, the role of dose-escalated radiotherapy in combination with long-term androgen deprivation treatment (ADT) is controversial, without any demonstrated benefit on cancer-specific or overall survival. We aimed to evaluate the effect of a 10 Gy dose increase, from 70 Gy to 80 Gy, on progression-free survival in men with high-risk prostate cancer. METHODS: In this multicentre, open-label, randomised, phase 3 trial, we enrolled patients with high-risk prostate cancer, defined as prostate-specific antigen of 20 ng/mL or more, Gleason score of at least 8, or clinical stage T3-T4, from 25 centres in France. Participants were randomly assigned (1:1) by minimisation, stratified by centre and previous pelvic lymph node dissection, to receive prostate-targeted dose-escalated external beam radiotherapy (80 Gy; 2 Gy per fraction for 8 weeks) or standard-dose external beam radiotherapy (70 Gy; 2 Gy per fraction for 7 weeks), combined with long-term ADT. Neither the participants nor the investigators were masked to the allocated treatment. The primary endpoint was 5-year progression-free survival defined as the time from randomisation to first biochemical (defined as prostate-specific antigen >nadir plus 2 ng/mL) or clinical (ie, local, regional, or metastatic) disease progression, analysed in the intention-to-treat population, with 197 events required. 5-year progression-free survival was the prespecified endpoint, and 10-year progression-free survival was additionally reported (post hoc) in view of the low number of events at 5 years. The trial is registered at ClinicalTrials.gov, NCT00967863, and is complete. FINDINGS: Between April 6, 2009, and Jan 24, 2013, 505 patients with high-risk prostate cancer were enrolled; 250 were assigned to receive dose-escalated radiotherapy (80 Gy) and 255 to receive standard dose radiotherapy (70 Gy). All participants were male and ethnicity data were not collected. At a median follow-up of 9·5 years (IQR 8·5-10·3), 5-year progression-free survival was 91·4% (95% CI 87·0-94·4) in the dose-escalation group versus 88·1% (83·2-91·6) in the control group, and 10-year progression-free survival was 83·6% (77·8-88·0) versus 72·2% (65·3-78·0; stratified HR 0·56, 95% CI 0·40-0·78, p<0·0001). Grade 3 or worse adverse events assessed at 6 months (acute toxicity) were observed in 60 (24%) of patients in the dose-escalation group and 62 (25%) in the control group. The most frequent grade 3 or worse adverse events were sexual disorders (28 [11%] in the dose-escalation group vs 20 [8%] in the control group) and bladder or urethra disorders (12 [5%] vs 19 [8%]). Adverse events assessed at 5 years (late toxicity) occurred in 118 (70%) of 168 in the dose-escalation group and 122 (73%) of 168 in the control group; grade 3 or worse late toxicities occurred in 19 (8%) participants in the dose-escalated radiotherapy group versus 17 (7%) participants in the control group. The most common late grade 3 adverse event was bladder or urethra disorders (seven [4%] vs three [2%], respectively). Serious adverse events occurred in nine (4%) patients in the dose escalation group and nine (4%) in the control group; none were considered to be treatment related. There were no treatment-related deaths. INTERPRETATION: For patients with high-risk prostate cancer, radiotherapy at a total dose of 80 Gy, in combination with long-term ADT, improved progression-free survival and could be a potential option in this situation. However, given the low number of events, further research is needed to consolidate and confirm the benefit in dose-escalation in prostate cancer-specific survival and overall survival. FUNDING: French National Cancer Institute and AstraZeneca.
Aged↗
Evaluation of the clinical and mechanistic role of MCM2 expression in the prediction of meningioma recurrence after radiotherapy.
OBJECTIVE: Postoperative radiotherapy is an effective treatment for meningiomas; however, treatment response varies among patients. In addition, practical methods for predicting tumor recurrence after radiotherapy have not been well established. Minichromosome maintenance protein 2 (MCM2), a key regulator of DNA replication licensing, was recently implicated in highly proliferative molecular subtypes of meningioma. In this study, the authors evaluated whether MCM2 immunohistochemical expression predicts response to radiotherapy in patients with meningiomas. METHODS: The authors retrospectively analyzed the records of patients with WHO grade 1-3 meningiomas treated with resection followed by radiotherapy at a single institution between July 2003 and November 2023. The MCM2 labeling index was assessed immunohistochemically, and patients were stratified into MCM2-high and -low groups using a cutoff of 35%. Progression-free survival (PFS) was defined as the interval from the completion of radiation therapy to postoperative radiological tumor recurrence or regrowth. Patients who showed no progression were censored at their last follow-up. PFS was estimated using Kaplan-Meier analysis and subsequently evaluated with Cox proportional hazards models. To further investigate the biological mechanisms associated with MCM2 expression, comprehensive transcriptomic analyses, including gene set enrichment analysis, was performed to elucidate the molecular processes that occur within MCM2-high tumors. RESULTS: The study population included 15 men (42%) and 21 women (58%), with a mean age of 63 years. Ten tumors (28%) were classified as MCM2-high meningiomas and 26 (72%) as MCM2-low meningiomas. High MCM2 expression was significantly associated with WHO grades 2-3 histology and higher Ki-67 labeling indices. During a median follow-up of 2.52 years, tumor progression after radiotherapy occurred in 47% of the patients. High MCM2 expression (HR 8.34, p = 0.03) was significantly associated with shorter PFS and remained an independent predictor of recurrence after adjustment for WHO grade, tumor size, and Ki-67 labeling index. Transcriptomic analyses of MCM2-high tumors revealed upregulation of cell proliferation-related pathways, accompanied by increased signaling through the E2F8-CHEK1 axis associated with radiation resistance and suppression of the TNF-α signaling pathway implicated in radiosensitivity. CONCLUSIONS: In meningiomas, high MCM2 expression is associated with early recurrence following radiotherapy. The study findings suggest that this association is driven by diverse biological mechanisms related to cell cycle regulation and radioresistance. Immunohistochemical assessment of MCM2 expression may serve as a practical and accessible biomarker for risk stratification and may support the future development of individualized postoperative radiotherapy strategies.
Humans↗
Evaluation of BCNU and/or radiotherapy in the treatment of anaplastic gliomas. A cooperative clinical trial.
A controlled, prospective, randomized study evaluated the use of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and/or radiotherapy in the treatment of patients who were operated on and had histological confirmation of anaplastic glioma. A total of 303 patients were randomized into this study, of whom 222 (73%) were within the Valid Study Group (VSG), having met the protocol criteria of neuropathology, corticosteroid control, and therapeutic approach. Patients were divided into four random groups, and received BCNU (80 mg/sq m/day on 3 successive days every 6 to 8 weeks), and/or radiotherapy (5000 to 6000 rads to the whole brain through bilateral opposing ports), or best conventional care but no chemotherapy or radiotherapy. Analysis was performed on all patients who received any amount of therapy (VSG) and on the Adequately Treated Group (ATG), who had received 5000 or more rads radiotherapy, two or more courses of chemotherapy, and had a minimum survival of 8 or more weeks (the interval that would have been required to have received either the radiotherapy or chemotherapy). Median survival of patients in the VSG was, best conventional care: 14 weeks (ATG: 17.0 weeks); BCNU: 18.5 weeks (ATG: 25.0 weeks); radiotherapy: 35 weeks (ATG: 37.5 weeks); and BCNU plus radiotherapy: 34.5 weeks (ATG: 40.5 weeks). All therapeutic modalities showed some statistical superiority compared to best conventional care. There was no significant difference between the four groups in relation to age distribution, sex, location of tumor, diagnosis, tumor characteristics, signs or symptoms, or the amount of corticosteroid used. An analysis of prognostic factors indicates that the initial performance status (Karnofsky rating), age, the use of only a surgical biopsy, parietal location, the presence of seizures, or the involvement of cranial nerves II, III, IV, and VI are all of significance. Toxicity included acceptable, reversible thrombocytopenia and leukopenia.
Adolescent↗
[Radiotherapy of inflammatory diseases -- indicated still today? (author's transl)].
The good response of inflammatory diseases to a low dose radiotherapy is well known. Mainly, this fact is based on experiences made in the time before antibacterial chemotherapy area. In this study our results are presented which were obtained by treating 90 patients with radiotherapy in the last years, exlusively. With respect to the end of the treatment a success rate of more than 90% was achieved. This result was compared with literature and with own findings from radiotherapy of patients with degenerative joint diseases. From the viewpoint of radio-protection the radiotherapy should be initiated as early as possible because in these cases better results could be attained at low doses. Especially, the radiotherapy of the following diseases seems to be favourable: parotitis, mastitis, abscess, furuncle, paronychia and panaritium. Besides the complications and risks of the chemotherapy the somatic and genetic radiation injuries are discussed. When radiation therapy is applied skilfully the side effects of a locally and regionally limited therapy may be neglected. It is recommended to extend the indication for radiotherapy of inflammatory diseases.
Abscess↗
[Contribution of radiotherapy in the local-regional treatment of breast cancer].
The role of radiotherapy in the treatment of mammary carcinoma is reviewed. The indication for postoperative radiotherapy in cases of primary tumors T2 and T3, particularly in the presence of metastatic lymph nodes (N1), is still given. For stage 1 (T1/T2 N0), postoperative radiotherapy may be omitted or can be limited to the lymphatic area which has not been surgically explored. Pre-operative radiotherapy for the more advanced stage (T3/T4 and N2) has proven more effective than postoperative irradiation. Radiotherapy as an exclusive procedure in the sense of a curative, non-mutilating treatment for small breast cancers(T1/T2 NO) provides, if correctly administered, the same 5- and 10-year survival rate at surgical amputation. The arguments against the use of radiotherapy (lymphopenia, diminished immunological reactions, frequency of hematogenic metastases) are discussed.
Aged↗
[Results of radiotherapy of bronchial carcinoma (author's transl)].
In a joint retrospective study by 17 radiotherapy clinics in German-speaking countries the results of treatment of bronchial carcinoma after radiotherapy were analysed in 7503 cases. The age peak was between the 60th and 70th year. Squamous-cell carcinoma was the most frequent histological type, followed by anaplastic carcinoma, with adenocarcinoma being rare. There was a high proportion of histologically not clearly identified cases (27% in central and 35% in peripheral carcinomas). Survival rate at one year was 31% for central (3662 patients) and peripheral (961 patients) tumours, but only 2% at five years. Prognostically there was no difference between histological types and kind of radiotherapy or technique, but total dose affected survival rate. At a total dose of less than 5000 rd the survival rate at five years was minimal. The prognosis of combined surgical and radiotherapeutic measures was slightly better than with a radiotherapy alone, but results were unpredictable for the individual case. It is concluded that radiotherapy aiming at cure should be used in imoperable bronchial carcinoma if the tumour state and general condition of the patient appear to make a cure possible. But if this is not the case, radiotherapy should be used only palliatively, i.e. only to ameliorate symptoms.
Adenocarcinoma↗
Synchronous VBM and radiotherapy in the treatment of squamous cell carcinoma of the head and neck.
Since April 1974, 60 patients with squamous cell carcinoma of the head and neck region, of poor prognosis and generally in advanced stages, were treated with the combination of a cytotoxic regimen--VBM (Vincristine, Bleomycin and Methotrexate) and radical radiotherapy. The essential feature of the combination is the administration of pulses of VBM synchronous with a course of fractionated external radiotherapy in order to achieve potentiation of radiotherapy. On average 4-5 pulses of VBM were given during treatment, combined with radiotherapy on a Cobalt unit. The selection, preparation and management of the patients are described. Intense mucositis and intercurrent infection provide the main problems during treatment and close management is essential. Late complications have not been a serious problem. The crude actuarial survival rate at 24 months is 61%. The probability of survival without any recurrence to 24 months following initial treatment is 46%. Local control was achieved by the initial treatment in 43 patients. These results suggest that potentiation of radiotherapy and an increased therapeutic ratio has been obtained by the addition of VBM to radiotherapy and there is a possibility that the occurrence of distant metastases has been reduced or postponed.
Bleomycin↗
Radiotherapy of Kaposi's sarcoma.
Between 1958 and 1976, 34 patients with Kaposi's sarcoma were seen. Two patients were kidney transplant recipients. Co-existing malignancies were seen in 22% of patients. From 1958 to 1965, cutaneous lesions were treated solely with local radiotherapy techniques, single doses of 800 rads being found adequate to produce a complete response. In 1965, because of the multicentric occurrence of the disease and frequent recurrences after local radiotherapy techniques, extended field radiotherapy was begun. Ten of twelve patients thus treated responded completely. It is concluded that extended field radiotherapy using a single dose of 800 rads offers complete relief of symptoms and better control of the disease when compared to local radiotherapy. There was very little morbidity, with the extended field technique.
Adult↗
The conservative management of anorectal cancer by radiotherapy.
Thirteen patients with an anal or rectal carcinoma were given curative radiotherapy. Four had medically inoperable tumors, one had a surgically inoperable tumor and eight refused abdominoperineal resection. Six patients received external radiotherapy only. Seven patients received external radiotherapy and an interstitial implant. Nine of thirteen patients (60 per cent) are alive without evidence of disease from fifteen to fifty-five months (average, 30 months). Six of seven patients who received external radiotherapy combined with an interstitial implant were controlled locally, whereas three of six patients who received external radiotherapy only were controlled. Patients who underwent total excision and/or fulguration prior to irradiation had better local control than those who underwent either biopsy only or a subtotal excision. This treatment method may be offered as an alternative to abdominoperineal resection in patients who are medically unfit or who refuse surgery.
Adenocarcinoma↗
[Semi-deep radiotherapy under high-kilovoltage conditions].
The semi-deep radiotherapy, performed by high-kilovoltage technique, fills a gap between superficial and megavolttherapy, as it renders possible an irradiation in focal depth of 2--4 cm, while largely preserving the deep underlying tissue. Besides which, every form of radiotherapy can be used, as under conventinal conditions. A further advantage exists in the markedly greater skin tolerance and in the low bone absorption of high-kilovoltage radiation, so that much higher focal doses can be achieved. This means that--in superficial processes--the high-voltage technique can replace the much more expensive therapy with accelerated electrons. The RT 305 equipment for high-voltage technique can be especially recommended for the following indications: 1. Skin and limph node metastases as well as tumors and metastases which are not situated deeper than 5 cm below the skin surface. Hereby, thean be exposed up to 8000 R, by small or medium cone. At the same time, in comparison to conventional X-ray therapy, the deep tissue is largely preserved. 2. Postoperative radiotherapy of tumors situated right under the skin. 3. Radiotherapy of inoperable breast cancer. 4. Irradiation of relapses on pre-exposed skin. 5. We assume that the high-voltage technique is also suitable for primary radiotherapy of larynx carcinomas, although we have no personal experience of this. 6. The palliative irradiation of deep tumors with the RT 305, due to its preservation of the skin and the relatively low bone absorption, can be performed more easily than with conventional X-ray therapy. The method of choice, however, is the megavolt-therapy. 7. Degenerative diseases and arthroses.
Adult↗
Preoperative radiotherapy in operable breast cancer: results in the Stockholm Breast Cancer Trial.
A randomized trial of preoperative radiotherapy in operable breast cancer was conducted from 1971 to 1976. The diagnosis was established by fine-needle aspiration biopsy. A dose of 4500 rad over five weeks was given to the chest wall, the breast and the lymph nodes of the axilla, the supraclavicular fossa and the internal mammary chain. Modified radical mastectomy was performed six weeks or more after completed radiotherapy. In control patients the same operation was performed without prior radiotherapy. By random allocation, one control group received no further treatment and postoperative irradiation was given to the other controls. Preoperative radiotherapy reduced the incidence of local and regional recurrence and of distant metastases, and also the mortality, as compared with the surgery only group. Postoperative radiotherapy as given in this trial gave almost equal reduction of local and regional recurrence but did not diminish the frequency of distant metastases or the mortality.
Adult↗
The clinical value of adding immune checkpoint inhibitors to radiotherapy for cancer: a systematic review and meta-analysis.
BACKGROUND: While several randomized clinical trials (RCTs) have explored the addition of immune checkpoint inhibitor (ICI) treatment for patients undergoing radiotherapy, studies systematically assessing the clinical value of such interventions are lacking. METHODS: PubMed, Embase, and Cochrane Library databases were searched for relevant RCTs of cancers that received ICIs plus radiotherapy or radiotherapy. Eligible studies were those published in English as of 14 April 2024. Two independent reviewers screened the included studies and extracted relevant data, then selected the random or fixed-effects model based on the I2 statistic. The main outcomes were hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival (OS) and progression-free survival (PFS); Odds ratios (ORs) with 95% CIs for objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). Stratified analysis was performed based on cancer type, ICI type, and the timing of ICI addition. The study was registered on PROSPERO (CRD42024551008). RESULTS: 15 RCTs with 7947 patients were included. Pooled HRs were 0.865 (95% CI, 0.730-1.000; I2 = 72.1%) for OS and 0.799 (0.677-0.922; I2 = 82.0%) for PFS in cancer patients. In cancer types, adding immunotherapy to radiotherapy significantly improved patients with non-small-cell lung cancer (OS: 0.544 [0.371-0.717]; PFS: 0.527 [0.438-0.617]) and cervical cancer (OS: 0.722 [0.578-0.867] and PFS: 0.754 [95%CI, 0.621-0.887]). Regarding the ICIs schedule, adjuvant ICI therapy with pooled HRs was 0.742 (0.649-0.834) for OS and 0.638 (0.579-0.697) for PFS. In addition, the pooled ORs for the incidence of grade 3 or higher treatment-related and immune-related adverse events were 1.227 (1.059-1.421; I2 = 71.9%) and 2.217 (1.743-2.821; I2 = 74.0%), respectively. CONCLUSION: Adding immunotherapy to radiotherapy can provide significant clinical benefits for patients with NSCLC and cervical cancer, and the addition of these ICIs in the adjuvant stage is supported.
Humans↗
Combined-modality oncotherapy with cyclophosphamide (NSC-26271) and radiotherapy: control of murine mastocytoma.
We investigated the effects of cyclophosphamide, alone and in combination with a 1,000-R/week radiotherapy schedule, on the growth of solid P815X2 tumors in 12-week-old male DBA/2 mice. Single-dose treatments of 150 mg cyclophosphamide/kg were given to animals bearing tumors of different ages. Such treatment of young tumors resulted in proportionately greater degrees of regression and steeper regrowth curves than did treatment of older tumors. Although slopes of regrowth curves differed greatly, time to regrowth (to pretreatment size) was the same for all age classes of tumors. Graded weekly exposures of 50-250 mg/kg for 4 weeks resulted in dose-dependent increases in incidence of complete remission, duration of remission (time to regrowth), and mean animal life-spans. The combination of radiotherapy to the tumor and 75, 150, or 225 mg cyclophosphamide/kg/week resulted in better local tumor control than occurred with radiotherapy or the drug alone. However, a dose-dependent increase in radiosensitivity of the gastrointestinal mucosa included in radiotherapy fields was observed. A 3-week course of radiotherapy plus 75 mg cyclophosphamide/kg/week (which is tolerated by the mucosa) increased animal lifespans to 165% of those of controls.
Animals↗