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PubMed2026

The role of particle therapy in the treatment of locally recurrent rectal cancer: a systematic review.

BACKGROUND: Colorectal cancer is a common malignancy. Advancements in multimodality treatment have improved outcomes. About 2-10% of patients will have a local recurrence even after optimal treatment. Salvage surgical treatment is the treatment of choice, however, in posterior and lateral recurrences, surgery is linked to a high rate of treatment-related morbidity. Some recurrences remain unresectable even after neoadjuvant treatment. MATERIALS AND METHODS: A systematic literature review was performed to search for studies on curative-intent radiation therapy (RT) with photons, stereotactic body radiation therapy (SBRT) and particle beam therapy. The aim of the literature search was to define the role of particle therapy in the treatment of patients with unresectable or inoperable local recurrences of rectal cancer where neoadjuvant treatment is unlikely to result in downstaging, leaving patients with RT as the only curative treatment option. RESULTS: 32 studies which fulfil the criteria were identified. In general, SBRT and particle beam therapy permitted the application of significantly higher doses to the target without a concomitant increase in treatment-related toxicities. CONCLUSIONS: For unresectable and inoperable locally recurrent rectal cancer ablative radiotherapy techniques such as SBRT and particle beam therapy offer a curative treatment approach as an alternative to surgery. SBRT can be offered for small local and nodal recurrences, while particle beam therapy can be offered for larger recurrences and complex shapes spanning several anatomical compartments as well. Further research is needed to stratify patients according to their need and eligibility for the different possible modalities of curative-intent RT.

Humans↗

PubMed1992

Salvage radiotherapy in recurrent Hodgkin's disease.

Forty-four patients with Hodgkin's disease (HD) which relapsed after chemotherapy were treated with salvage radiotherapy (S-RT) with curative intent. Patients were aged 7 to 80 years (median 32 years) at the time of S-RT and the median follow-up from S-RT was 5 years (1-15). Nine patients had recurrent HD following first-line chemotherapy and thirty five patients had refractory HD. Salvage therapy consisted of radiotherapy alone in 25 and combined chemotherapy and radiotherapy in 19 patients. The overall CR rate of salvage therapy was 66%. The overall median survival of 44 patients was 4.6 years from S-RT with 46% 5 year and 40% 10 year survivals. Age (greater than 40 years) and progression free interval (less than or equal to 1 year) were adverse independent prognostic factors for survival on multivariate analysis. The 5 and 10 year progression free survivals were 38% and 23% respectively. Adverse independent prognostic factors for progression-free survival were extranodal site of recurrence and short progression free interval (less than or equal to 1 year). We conclude that radiotherapy with or without chemotherapy has a role in the salvage of patients failing chemotherapy, particularly in those with nodal disease and progression-free interval greater than 1 year.

Adolescent↗

PubMed1991

Larynx preservation using induction chemotherapy plus radiation therapy as an alternative to laryngectomy in advanced head and neck cancer. A long-term follow-up report.

Since 1977, we have used induction chemotherapy (CT) plus radiation therapy (RT) with curative intent in 35 advanced head and neck cancer (Ca) patients who otherwise would have required total laryngectomy. Fourteen patients had advanced Ca of the larynx or supraglottic larynx (SGL); 21 patients had Ca of the hypopharynx. In six patients the Ca was Stage III; in 26 patients it was Stage IV. Three patients had Stage II disease--2 with cancer of the pyriform sinus and one patient with Stage II SGL Ca who refused surgery. Chemotherapy consisted of platinum (P) + bleomycin in 18 patients until 1982, then P + fluorouracil in the next 17 patients. Total response rate was 77%--complete (CR) in 26% and partial (PR) in 51%. There were two toxic deaths. Surgery was limited to tracheostomy in 4 patients prior to CT and to radical neck dissection after CT in 4 others. Two patients required salvage laryngectomy at 11 and 31 months, respectively. One patient underwent partial laryngectomy with voice preservation. Thirty-two patients were evaluable for overall response after RT. Final disease-free status was achieved in 20/34. One long-term survivor was lost to follow-up (44 months) and 8 patients remained alive at 13+ to 109+ months. Median failure-free survival for all patients was no less than 24 months. Not counting 4 early deaths free of disease, 2-year local control using only chemotherapy plus radiation was 52% (16:31). Overall, 33 of 35 patients retained their voices. Sixteen patients (46%) have survived 2 years or longer. Survival of patients who achieved CR after induction chemotherapy was 48 months versus 14 months for those with less than a CR (p = 0.001). Patients with a hypopharyngeal primary had only a 33% 2-year local control rate with chemotherapy and radiation and a median survival of only 12 months versus 77% control and a minimum 39-month survival for those whose tumor arose in the larynx (p = 0.009). Induction chemotherapy plus radiation therapy is an effective strategy which can produce a high rate of larynx preservation, local control, and long-term survival in patients with advanced cancer of the larynx. Patients with hypopharyngeal primaries have a lesser rate of long-term survival and local control, despite similar overall response rates.

Aged↗

PubMed1979

Sterilization of cerebral metastases by radiation therapy.

It is generally acknowledged that radiation therapy (RT) provides effective palliative treatment for the majority of patients with brain metastases. It is less well known that RT can be "curative." In 10 years, we examined five patients with brain metastases treated with whole-brain radiotherapy and with no residual tumor in the brain at autopsy. These five patients represented about 3 percent (5 of 187) of patients treated for brain metastases and later examined at autopsy. Some metastatic brain tumors are eradicated by RT, and all nonterminal patients should be offered such treatment.

Adenocarcinoma↗

PubMed1991

Curative radiotherapy following chemotherapy for invasive bladder carcinoma (a preliminary report).

Twenty-five patients with invasive transitional cell carcinoma of the bladder (Stage T2, T3, T4) received combined modality therapy using four cycles of methotrexate, vinblastine, adriamycin, and cisplatin (MVAC) chemotherapy followed by surgery or radiation therapy (RT). Sixteen patients had complete (N = 8) or partial (N = 8) response to MVAC. Curative RT was delivered to 11 responders with T2 or T3 disease and to 2 patients with T4 disease. All 11 with T2 and T3 disease are currently alive, 7 with normal bladder function. The two with T4 disease are dead of disease. Three patients required salvage cystectomy for local recurrence and one patient had cystectomy for bladder stones. Follow-up ranged from 11 to 50 months with a median of 31 months. No late chemo-radiotherapy treatment-related complications to the intestines or in bladder function (other than one bladder stone formation) occurred. These preliminary results are encouraging and warrant further evaluation of this innovative approach in treating invasive carcinoma of the bladder. T2 and T3 patients with a complete or partial response to MVAC may be excellent candidates for a bladder-sparing treatment.

Adult↗

PubMed1992

Influence of age, prior abdominal surgery, fraction size, and dose on complications after radiation therapy for squamous cell cancer of the uterine cervix. A patterns of care study.

The 1973 and 1978 national surveys conducted by the Patterns of Care Study (PCS) for squamous cell cancer of the uterine cervix were combined to analyze factors associated with complications after radiation therapy (RT). Overall, 1558 patients were reviewed, with a median follow-up of 43 months. Major complications (defined as necessitating hospitalization for management) were seen in 152 of 1558 (9.8%) patients, with a 5-year actuarial rate of 14%. A number of pretreatment and treatment factors were analyzed with respect to complications. In univariate analysis, significant pretreatment and treatment factors associated with an increase in complications included young age, prior laparotomy for staging, history of prior abdominal surgery, increasing stage, use of external RT, high fraction size, cesium source, and high paracentral (PCS point A) and lateral (PCS point P) doses. Multivariate analysis showed a history of prior abdominal surgery, paracentral dose greater than 7500 cGy, use of cesium, daily fraction size greater than 200 cGy, and age younger than 40 years to be associated independently with complications. A detailed analysis of the type of and time to complications is presented. The knowledge and skillful management of these pretreatment and treatment factors may improve the therapeutic ratio for RT, which is the most active curative modality against cervical cancer.

Adult↗

PubMed1992

Bulky endocervical carcinoma: a 23-year experience.

Between 1962 and 1985, 371 patients had initial treatment for bulky endocervical carcinomas of the uterine cervix at The University of Texas M.D. Anderson Cancer Center. All patients had concentric expansion of the cervix by tumors that measured at least 6 cm in greatest transverse diameter. Of the 361 patients treated with curative intent, 211 (57%) had FIGO Stage I disease that was believed to be confined to the uterus, 59 (16%) had FIGO Stage IIA disease, and 101 patients (27%) had FIGO Stage IIB disease. Median follow-up time of surviving patients was 130 months. Actuarial survival rates of 361 patients treated with curative intent were 54% and 48% at 5 and 10 years, respectively. The actuarial pelvic disease control rate was 76% at 10 years. Patients whose tumors were less than 8 cm in maximum diameter (279 patients) had a better survival rate than those with tumors greater than or equal to 8 cm in diameter (92 patients) (p less than 0.01). Of the 282 patients who underwent lymphangiography, survival rate was significantly better for those with negative studies than it was for the 113 patients (40%) with positive or suspicious studies (p less than 0.01). There was no correlation between FIGO stage and survival rate (p = 0.64) or pelvic control rate (p = 0.59). Of patients treated with curative intent, treatment was by radiation alone (RT) in 244 (68%) or by radiation followed by hysterectomy (RT+S) in 117 (32%). Although there has been an overall shift in policy away from the use of adjuvant hysterectomy during the past decade, many patient selection factors also influenced the choice of treatment during the study years, resulting in a significantly higher proportion of patients with adverse prognostic features in the RT group. Patients chosen for treatment with RT alone had a greater likelihood of having tumors greater than or equal to 8 cm (p = 0.03), FIGO stage IIB (p less than 0.01), positive lymphangiogram (p = 0.02), and persistent palpable parametrial disease after external radiotherapy (p less than 0.01). Patients treated with RT alone also had a lower overall survival rate at 10 years than patients treated with RT+S (45% vs 64%, p less than 0.01). Although multivariate analysis suggested that treatment had an independent influence upon survival rate, it was difficult to draw firm conclusions about the value of adjuvant surgery because of the numerous biases in patient selection, some of which may have been difficult to quantify.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

PubMed1991

Adjuvant post-operative radiotherapy in rectal cancer: results from the ANZ Bowel Cancer Trial (Protocol 8202).

In July 1982 the Gastrointestinal Section of The Clinical Oncological Society of Australia began a multicentre randomized trial to assess the value of post-operative pelvic radiotherapy in the local control of stage B and C carcinoma of the rectum. Patients who had undergone a potentially curative resection were randomized either to no further treatment (NO RT) or to pelvic radiotherapy (RT), 45 Gy in 25 fractions (plus a perineal boost of 5 Gy in 2 fractions after abdomino-perineal resection). The trial was prematurely terminated in December 1985 owing to slow accrual after 70 patients had been randomized: 36 patients to RT and 34 patients to NO RT. Two patients in each group were found to be ineligible after randomization and, for a variety of reasons, thirteen patients who were randomized to RT did not receive that treatment. The incidence of post-operative complications were comparable in both groups, indicating that radiotherapy produced no additional problems. Radiotherapy-related morbidity comprised mainly diarrhoea (grade 1 = 2/21; grade 2 = 5/21; grade 3 = 0/21; grade 4 = 1/21). There were no deaths due to radiotherapy and only one patient, with grade 4 diarrhoea, failed to complete the prescribed course of radiotherapy. After an average follow-up period of 52 months there were 15 local recurrences, 8 in the RT group and 7 in the NO RT group, giving an actuarial 2 year local recurrence rate of 16%. There was no difference in the time to local recurrence, either by randomization group (p = 0.50) or by actual treatment received (p = 0.91).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

PubMed1978

Limited epithelial carcinoma of the ovary treated with curative intent by the intraperitoneal installation of radiocolloids.

Between January 1960 and September 1972, 104 patients with limited epithelial carcinoma of the ovary received intraperitoneal radiocolloid. Fifty-six of these patients also received external beam radiation therapy to the pelvis (pelvic RT). Five-year actuarial no-evidence-of-disease survival rates were 95% for stage Iai, 82% for Iaii, 73% for Ib, 67% for Ic, 67% for IIa, 67% for IIb without gross residual tumor (GRT), 25% for IIb with GRT, and 50% for III with minimal or no GRT. The addition of pelvic RT following radiocolloid could not be shown to affect survival of patients with Stage I and IIa tumors. Small bowel complications were related to the use of pelvic RT, however, occurring in 2.2% of patients treated with radiocolloid alone and 24% of patients treated with colloid and pelvic RT (p less than 0.005). In patients who underwent abdominal surgery following treatment of ovarian cancer, no excessive complication rate was observed. We conclude that for patients with stages Iaii through IIa, postoperative radiocolloid appears to provide the greatest chance of survival with the least chance of complication. For patients with Stage IIb and III lesions in whom there is minimal or no GRT, radiocolloid followed by pelvic RT produced survival rates comparable or superior to any other form of postoperative therapy.

Adult↗

PubMed2026

Landscape of retron diversity across the SPIRE microbial metagenome resource reveals candidate novel type XI-like lineages.

Retrons are bacterial genetic elements encoding a specialized reverse transcriptase (RT) that synthesizes multicopy single-stranded DNA and are increasingly recognized as components of bacterial anti-phage defense systems. However, their diversity and ecological distribution across large-scale genomic resources remain poorly characterized. Here, we surveyed retron RTs across the SPIRE representative metagenome collection, a non-redundant, species-level data set spanning diverse microbial habitats. Using a curated panel of type-specific hidden Markov models, we identified retrons representing all canonical types together with additional divergent lineages. Retron distribution showed strong taxonomic and ecological structuring, with some groups restricted to specific bacterial phyla, whereas others were broadly distributed across environmental categories. Systematic novelty assessment identified two candidate type XI-like lineages, TXI_C2like and TXI_noncan_h, characterized by protease-independent architectures and distinct accessory modules associated with WYL- and DnaB_C-containing proteins, respectively. De novo covariance-based analyses further identified candidate msr/msd-like non-coding RNA structures in both lineages, supporting conservation of the canonical RT-ncRNA organizational framework despite extensive sequence divergence. Together, these findings expand the known diversity of retron systems and identify type XI-like retrons as a dynamic and previously underexplored evolutionary group.IMPORTANCERetrons are bacterial genetic elements that are increasingly exploited as programmable tools for genome editing, molecular recording, and biosensing in addition to their natural role in anti-phage defense. Despite this growing biotechnological interest, the true diversity of retrons across the bacterial world has remained largely unmapped. By mining a resource of over 100,000 processed microbial metagenomes, we uncovered thousands of retron sequences spanning known types as well as previously unrecognized lineages and found that their distribution is strongly shaped by both bacterial taxonomy and ecological niche. Among these, we identified two candidate new lineages related to type XI retrons that lack the protease domain typical of this group but instead carry distinct accessory proteins, expanding the known architectural diversity of these systems. These findings broaden the catalog of retron diversity available for functional characterization and biotechnological engineering and provide a framework for prioritizing candidate lineages for future experimental validation.

effectors↗

PubMed1992

Relaxation therapy as an adjunct in radiation oncology.

Stress, anxiety, and depression in patients who are undergoing treatment of cancer significantly compromise the quality of their lives. The impact of stress reduction by relaxation training and imagery was studied in 82 out-patients who were undergoing curative (73 patients) or palliative (9 patients) radiotherapy. Fifty-two females and 30 males were assigned randomly to a relaxation training condition (34 patients) as an adjunct to radiation or a control condition (29 patients), which entailed education and counseling along with the RT. Using pre- and posttests of the Profile of Mood States, significant (p less than .01) reductions were noted in the treatment group in tension, depression, anger, and fatigue. The results suggest that relaxation training substantially improves several psychological parameters associated with quality of life in ambulatory patients who are undergoing radiation therapy.

Adult↗

PubMed1992

[Anaplastic carcinoma of the thyroid. Our experience].

Nineteen patients, 12 females and 7 males, with mean age of 66 years, with anaplastic carcinoma of the thyroid, were treated between 1976 and 1990. At diagnosis, in 4 patients disease presented as intraglandular mass, in 11 as infiltration of the adjacent structures and as distant metastases in 4 cases. A preceding history of goiter was found in 7 patients. Total thyroidectomy was performed in 9 patients, subtotal thyroidectomy in 1 and a diagnostic biopsy only in 4 cases. All patients received external radiotherapy (4000-6000 rads). Median global survival was 6 months with no difference between patients receiving thyroidectomy plus RT or biopsy plus RT. All patients died of tumor except 1 who is alive and free of disease at 120 months. Combination modality treatment of anaplastic carcinoma of the thyroid represent, at times, a rational palliative therapeutic approach, even if, in selected patients with early intraglandular disease, total surgery may represent a curative therapy.

Adult↗

PubMed1992

Consolidation hemibody radiotherapy following induction combination chemotherapy in high-tumor-burden multiple myeloma.

PURPOSE: Curative therapy for multiple myeloma continues to be an elusive goal. This report discusses the Northern California Oncology Group (NCOG) phase I and II trial in high-tumor-burden disease that used a strategy that consisted of induction chemotherapy (vincristine, melphalan, cyclophosphamide, and prednisone [VMCP]) for eight cycles followed by sequential hemibody radiation therapy (RT) and subsequent chemotherapy for an additional eight cycles. PATIENTS AND METHODS: Seventy-two previously untreated stage III myeloma patients were entered onto the study. Sixty-nine received induction chemotherapy, 40 received induction chemotherapy and hemibody RT, and 23 received induction chemotherapy, hemibody RT, and consolidative chemotherapy. RESULTS: Twenty-two complete responses (CRs) were obtained by induction chemotherapy, with four additional CRs after RT and consolidative chemotherapy. Nineteen patients developed grade 4 hematologic toxicity primarily after upper hemibody RT. Eight of these developed long-standing neutropenia or thrombocytopenia. Median survival of the group was 134 weeks, which was not significantly different from other approaches. CONCLUSIONS: Hemibody RT can be combined with chemotherapy as induction therapy and can be safely administered in a community setting. However, as administered here no survival advantage was demonstrated.

Adult↗

PubMed1992

Initial combined cryotherapy and irradiation for unresectable non-small cell lung cancer. Preliminary results.

In unresectable non-small cell lung cancer (NSCLC) with a patent mainstem bronchus, some studies of obstructive tumors, showed (1) a poor role for irradiation in obtaining efficient debulking and (2) an interest in preliminary laser treatment in these patients. Cryotherapy is another method to obtain debulking. Moreover, several studies showed that cryotherapy would increase the radiosensitivity of a tumor. We performed a preliminary protocol combining successively initial cryotherapy followed by irradiation in inoperable NSCLC (either for local or functional contraindications). Thirty-eight patients were included and treated first by cryotherapy performed under general anesthesia and then with external irradiation in a curative intent. The efficiency of cryotherapy assessed on bronchoscopy was found to be volume-efficient (VE) in 26 of the 38 patients and non-volume-efficient (NVE) in the other 12 patients. After irradiation in the VE group, 17 of the 26 patients had no bronchial residual tumor (NRT). In contrast, all of the patients in the NVE group had a bronchial residual tumor (RT). Survival in the VE group (median, 397 days) was significantly higher than the survival of the NVE group (median, 144 days). Survival was found to be independent of the surgical contraindication (local or functional). The best survival was associated both with the efficiency of the initial debulking (VE) by cryotherapy and with the local control (NRT) induced by the irradiation (median, 560 days). Local control was obtained in 65 percent (17/26) of the cases in the VE group and was never observed in the NVE group. In our study the VE group's local control is better than the 35 percent usually reported after irradiation alone. These results argue for the efficient potentiation of irradiation by cryotherapy.

Adult↗

PubMed2026

RNA splicing evidence enables robust classification of BRCA1 exon 18 variants: Results from the ENIGMA consortium.

The Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) research consortium conducted a comprehensive study to characterize spliceogenic variants in BRCA1 exon 18. The absence of systematic RNA-based assessment for these variants has led to inconsistent interpretation, limiting accurate classification and management of individuals and their families. The splicing profile of 166 variants was assessed using minigene assays; 32 were additionally analyzed in blood-derived RNA from 51 individuals and 18 in mouse embryonic stem cell (mESC)-based assays to evaluate homology-directed repair (HDR) capacity. mRNA assessment by RT-PCR in blood samples and minigene assays showed a significant positive correlation, with splicing analysis in mESCs displaying highly concordant results. The mESC-based HDR assay showed that the in-frame exon 18 skipping (Δ18) transcript encodes a non-functional protein lacking rescue activity. Linear regression analysis using mESC splicing and functional data indicated that ≥59% of full-length (FL) levels and <34% of Δ18 were associated with benign HDR activity. These thresholds differ from those recommended by the ClinGen ENIGMA BRCA1 and BRCA2 Variant Curation Expert Panel American College of Medical Genetics and Genomics (ACMG)/Association for Molecular Pathology (AMP) specifications for applying BP7_strong(RNA): >30% functional transcripts or <70% non-functional transcripts. Incorporation of RNA splicing evidence into variant interpretation increased pathogenic (28.6%-31.7%) and benign (3.7%-24.4%) classifications while reducing likely pathogenic (19.5%-17.7%), uncertain (18.9%-8.5%), and likely benign (29.3%-17.7%) categories. Experimental mRNA profiling impacted the interpretation of 34% of variants and resolved uncertainty in approximately 10% of cases. Exon 18 skipping was less tolerated, indicating that the degree of splice perturbation required to impair BRCA1 function may depend on the nature of the resulting non-functional transcript.

Humans↗

PubMed2026

Lipid Metabolism-related lncRNA Model Identifies AC026412.3 as a Driver of Fatty Acid β-oxidation in Hepatocellular Carcinoma.

BACKGROUND AND AIMS: Dysregulated lipid metabolism contributes to hepatocellular carcinoma (HCC) progression, but the prognostic value and mechanistic roles of lipid metabolism-related long noncoding RNAs (LRLs) remain insufficiently characterized. This study aimed to construct and validate an LRL-based prognostic model and to investigate the biological function and metabolic mechanism of AC026412.3 in HCC. METHODS: Transcriptomic and clinical data from the The Cancer Genome Atlas Liver Hepatocellular Carcinoma cohort were analyzed to identify LRLs based on their correlation with curated lipid metabolism genes. Differential expression, univariate Cox, least absolute shrinkage and selection operator (LASSO), and multivariate Cox analyses were performed to construct a prognostic signature, which was evaluated using Kaplan-Meier survival and time-dependent receiver operating characteristic (ROC) analyses. Functional enrichment analyses Gene Ontology [GO], Kyoto Encyclopedia of Genes and Genomes [KEGG] and gene set enrichment analysis [GSEA], mutation profiling, tumor mutational burden, immune infiltration estimation, and consensus clustering were applied to characterize associated features. A key LRL was identified through integrated bioinformatic screening and prioritization. Its biological role was assessed by quantitative reverse transcription polymerase chain reactionq (RT-PCR), western blotting, BODIPY staining, colony formation, Transwell assays, and xenograft models. RNA sequencing followed by pathway enrichment analysis was conducted to explore underlying mechanisms. RESULTS: A three-LRL signature (AL031985.3, NRAV, and AC026412.3) stratified HCC patients into distinct risk groups with significantly different survival outcomes and demonstrated independent prognostic value. AC026412.3 was markedly upregulated in HCC and associated with poor prognosis. Functional assays demonstrated that AC026412.3 promoted proliferation, invasion, and tumor growth while reducing lipid accumulation. Mechanistically, AC026412.3 upregulated solute carrier family 22 member 5 (SLC22A5), enhanced fatty acid β-oxidation, and increased adenosine triphosphate (ATP) production, thereby driving metabolic reprogramming. CONCLUSIONS: This study establishes a robust LRL-based prognostic model and identifies AC026412.3 as a key regulator of lipid metabolic reprogramming via the SLC22A5-fatty acid β-oxidation axis, highlighting its potential as a biomarker and therapeutic target in HCC.

HCC↗