Concomitant Chemoradiation Therapy Research Articles

Is the gemcitabin cisplatin doublet the optimal induction chemotherapy for non-Asian patients with NPC? Insights from a northeastern Moroccan cohort.

e18057 Background: According to the latest guidelines for NPC, induction chemotherapy followed by concomitant chemoradiation therapy (CCRT) is recommended as the preferred standard of care for patients with locally advanced nasopharyngeal carcinoma (stage III-Iva). However, the optimal regimen for induction chemotherapy (IC) in patients with locally advanced NPC remains uncertain. Methods: We conducted a retrospective study between January 2016 and October 2022 at the "CHU Hassan II" Oncology Hospital in Fes, Morocco, to compare the efficacy and tolerability of two platinum-based induction therapy regimens: cisplatin gemcitabine (GC) and cisplatin doxorubicin (DP), in the treatment of newly diagnosed locally advanced NPC. The main objectives of this study were to compare the efficacy including objective response rates (ORR), PFS ,OS and safety. Results: After eligibility assessment, we included 105 cases (62 patients in the DP group and 43 in the GC group), including 65 men and 40 women, with a mean age of 49.5 years (range = 19-79years) and a Karnofsky score ranging from 87% to 100%. 34% of patients were diagnosed at stage IVA. In the DP group, 3% of patients (2 out of 62) achieved a complete response CR, 60% achieved a partial response PR,25% remained stable SD and 19% experienced progression. In the GC group, 2% of patients (1 out of 43) achieved a CR, 39.5% achieved a PR, 39.5% remained stable, and 19% experienced progression. A statistically significant difference in PR was observed between the two groups (p = 0.028) ,and the difference in terms of progression is approaching the limit of significance (p=0,06) after a median follow-up of 27 months (5,3 -82). The 2-year progression-free survival (PFS) was 70% in the DP group compared to 80% in the GC group; the 2-year overall survival (OS) was 75% in the DP group and 90% in the GC group. No significant survival difference was observed between the two groups Patients in the DP group exhibited less grade 3-4 thrombocytopenia but more grade 3-4 leukopenia and neutropenia compared to the GC group. Conclusions: In patients with locally advanced nasopharyngeal carcinoma, GC-based induction chemotherapy demonstrated superior ORR over the DP regimen with acceptable toxicities. Further studies are needed to validate these results.

Comparative analysis of simultaneous integrated boost and sequential boost radiotherapy in node-positive cervical cancer: dosimetric and radiobiological considerations.

For locally advanced cervical cancer, the standard therapeutic approach involves concomitant chemoradiation therapy, supplemented by a brachytherapy boost. Moreover, an external beam radiotherapy (RT) boost should be considered for treating gross lymph node (LN) volumes. Two boost approaches exist with Volumetric Intensity Modulated Arc Therapy (VMAT): Sequential (SEQ) and Simultaneous Integrated Boost (SIB). This study undertakes a comprehensive dosimetric and radiobiological comparison between these two boost strategies. The study encompassed ten patients who underwent RT for cervical cancer with node-positive disease. Two sets of treatment plans were generated for each patient: SIB-VMAT and SEQ-VMAT. Dosimetric as well as radiobiological parameters including tumour control probability (TCP) and normal tissue complication probability (NTCP) were compared. Both techniques were analyzed for two different levels of LN involvement - only pelvic LNs and pelvic with para-aortic LNs. Statistical analysis was performed using SPSS software version 25.0. SIB-VMAT exhibited superior target coverage, yielding improved doses to the planning target volume (PTV) and gross tumour volume (GTV). Notably, SIB-VMAT plans displayed markedly superior dose conformity. While SEQ-VMAT displayed favorable organ sparing for femoral heads, SIB-VMAT appeared as the more efficient approach for mitigating bladder and bowel doses. TCP was significantly higher with SIB-VMAT, suggesting a higher likelihood of successful tumour control. Conversely, no statistically significant difference in NTCP was observed between the two techniques. This study's findings underscore the advantages of SIB-VMAT over SEQ-VMAT in terms of improved target coverage, dose conformity, and tumour control probability. In particular, SIB-VMAT demonstrated potential benefits for cases involving para-aortic nodes. It is concluded that SIB-VMAT should be the preferred approach in all cases of locally advanced cervical cancer.

Interaction of low-energy electrons with radiosensitizers.

We provide an experimentalist's perspective on the present state-of-the-art in the studies of low-energy electron interactions with common radiosensitizers, including compounds used in combined chemo-radiation therapy and their model systems. Low-energy electrons are important secondary species formed during the interaction of ionizing radiation with matter. Their role in the radiation chemistry of living organisms has become an important topic for more than 20 years. With the increasing number of works and reviews in the field, we would like to focus here on a very narrow area of compounds that have been shown to have radio-sensitizing properties on the one hand, and high reactivity towards low-energy electrons on the other hand. Gas phase experiments studying electron attachment to isolated molecules and environmental effects on reaction dynamics are reviewed for modified DNA components, nitroimidazoles, and organometallics. In the end, we provide a perspective on the future directions that may be important for transferring the fundamental knowledge about the processes induced by low-energy electrons into practice in the field of rational design of agents for concomitant chemo-radiation therapy.

A random graph-based neural network approach to assess glioblastoma progression from perfusion MRI

The identification of glioblastoma progression from the non-contrast enhancing areas is critically challenging to clinicians. This leads to poor prognosis and a very high local progression rate even after surgical resection and chemo-radiotherapy. Deep learning methods have been aiding in tracking tumor segmentation and progression. However, feature-based learning from these methods requires large datasets, multiple annotations, and measurements, resulting in complex, time-consuming networks. This work introduces a random Graph Neural Network (GNN) approach using two 16 × 16 random graph convolution layers to perform pixel-wise classification and predict glioblastoma progression from advanced perfusion MRI. A total of 17 patients, newly diagnosed with glioblastoma and treated with surgery and standard concomitant chemo-radiation therapy (CRT), were examined from The Cancer Imaging Archive Brain-Tumor-Progression dataset. Dynamic susceptibility contrast (DSC) MRI exams generated within 90 days following CRT completion and at clinically determined progression were evaluated for each patient. Three DSC modalities, such as normalized cerebral blood flow, normalized relative cerebral blood volume, and standardized relative cerebral blood volume were considered for the study. The proposed model provided an overall competitive accuracy of 99.76% with a training time of 6 minutes and a test time of 7.36 seconds. The proposed random GNN model demonstrates promising potential to predict final ground-truth maps accurately.

Dysregulation of SOX17/NRF2 axis confers chemoradiotherapy resistance and emerges as a novel therapeutic target in esophageal squamous cell carcinoma

BackgroundEsophageal squamous cell carcinoma (ESCC) is the sixth leading cause of cancer-associated death worldwide with a dismal overall 5-year survival rate of less than 20%. The standard first-line therapy for advanced ESCC is concomitant chemo-radiation therapy (CCRT); however, patients usually develop resistance, resulting in unfavorable outcomes. Therefore, it is urgent to identify the mechanisms underlying CCRT resistance and develop effective treatment strategies.MethodsPatients’ endoscopic biopsy tumor tissues obtained before CCRT treatment were used to perform RNA-seq and GSEA analysis. Immunohistochemical (IHC) staining, chromatin immunoprecipitation (ChIP), and promoter reporter analyses were conducted to investigate the relationship between SOX17 and NRF2. Xenograft mouse models were used to study the role of SOX17/NRF2 axis in tumor growth and the efficacy of carboxymethyl cellulose-coated zero-valent-iron (ZVI@CMC).ResultsIn this study, a notable gene expression signature associated with NRF2 activation was observed in the poor CCRT responders. Further, IHC staining of endoscopic biopsy of 164 ESCC patients revealed an inverse correlation between NRF2 and SOX17, a tumor-suppressive transcription factor with low expression in ESCC due to promoter hypermethylation. Using ChIP and promoter reporter analyses, we demonstrated that SOX17 was a novel upstream transcriptional suppressor of NRF2. In particular, SOX17low/NRF2high nuclear level significantly correlated with poor CCRT response and poor survival, indicating that the dysregulation of SOX17/NRF2 axis played a pivotal role in CCRT resistance and tumor progression. Notably, the in-house developed nanoparticle ZVI@CMC functioned as an inhibitor of DNA methyltransferases to restore expression of SOX17 that downregulated NRF2, thereby overcoming the resistance in ESCC. Additionally, the combination of ZVI@CMC with radiation treatment significantly augmented anticancer efficacy to inhibit tumor growth in CCRT resistant cancer.ConclusionThis study identifies a novel SOX17low/NRF2high signature in ESCC patients with poor prognosis, recognizes SOX17 as a transcriptional repressor of NRF2, and provides a promising strategy targeting SOX17/NRF2 axis to overcome resistance.

A Case Report of Traditional Korean Medicine-Based Integrative Oncology of Recurrent Cervical Cancer

Objective: To show a decrease in tumor recurrence and improvement in quality of life in patients with recurrent cervical cancer.Method: A 58-year-old female patient diagnosed with recurrent cervical cancer in February 2021 was treated for 14 months with integrative cancer treatment (ICT) to decrease the tumor size and improve chemotherapy-induced peripheral neuropathy (CIPN) and nausea. The patient underwent chemotherapy or concomitant chemoradiation therapy (CCRT) with ICT. Radiologic outcomes were assessed by abdomen & pelvis computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography-computed tomography (PET-CT) based on the Response Evaluation Criteria in Solid Tumors (RECIST) protocol. Clinical outcomes were assessed by the National Cancer Institute Common Terminology Criteria for Adverse Event (NCI-CTCAE), Eastern Cooperative Oncology Group (ECOG), and a numeric rating scale (NRS).Result: During the 14 months of treatment, the size and metabolic activity of the recurrent tumor decreased and underwent partial remission based on RECIST. The NRS scores for CIPN and nausea were improved, and the ECOG score improved from grade 2 to 1. No serious side effects of grade 3 or higher were noted on the NCI-CTCAE test.Conclusion: This case suggests that ICT may have a synergetic effect with chemotherapy or radiotherapy for recurrent cervical cancer.

Non-brachytherapy approach to treatment of locally advanced cervical cancer

Objective: Concomitant chemoradiation therapy (CRT) that includes both external beam radiotherapy (EBRT) and brachytherapy (BT) is the current standard of care in treatment of locally advanced cervical cancer (LACC). Volumetric modulated arc technology provides potential benefits allowing for dose escalation and decreased toxicities. This non-BT approach offers improved accuracy and no geographical miss due to adaptive radiotherapy, but oncologic outcomes still need to be evaluated.

Concomitant Chemoradiation Therapy with Gold Nanoparticles and Platinum Drugs Co-Encapsulated in Liposomes.

A liposomal formulation of gold nanoparticles (GNPs) and carboplatin, named LipoGold, was produced with the staggered herringbone microfluidic method. The radiosensitizing potential of LipoGold and similar concentrations of non-liposomal GNPs, carboplatin and oxaliplatin was evaluated in vitro with the human colorectal cancer cell line HCT116 in a clonogenic assay. Progression of HCT116 tumor implanted subcutaneously in NU/NU mice was monitored after an irradiation of 10 Gy combined with either LipoGold, GNPs or carboplatin injected directly into the tumor by convection-enhanced delivery. Radiosensitization by GNPs alone or carboplatin alone was observed only at high concentrations of these compounds. Furthermore, low doses of carboplatin alone or a combination of carboplatin and GNPs did not engender radiosensitization. However, the same low doses of carboplatin and GNPs administered simultaneously by encapsulation in liposomal nanocarriers (LipoGold) led to radiosensitization and efficient control of cell proliferation. Our study shows that the radiosensitizing effect of a combination of carboplatin and GNPs is remarkably more efficient when both compounds are simultaneously delivered to the tumor cells using a liposomal carrier.

Non-brachytherapy approach for locally advanced cervical cancer treatment.

e18023 Background: Concomitant chemoradiation therapy (CRT) that includes both external beam radiotherapy (EBRT) and brachytherapy (BT) is the current standard of care in treatment of locally advanced cervical cancer (LACC). Adaptive EBRT using volumetric modulated arc technology without BT allows dose escalation and decreases toxicities. Non-brachytherapy treatment is an evolving alternative approach provides geographical radiation accuracy but the oncological outcomes still to be evaluated. Methods: Patients with LACC (stages 1B3–IVA) who underwent non-brachytherapy CRT using adaptive EBRT with simultaneous integrated boost at our institution were evaluated prospectively from May 2015 to December 2019. All patients were initially assessed by a gynecologic oncologist, pelvic MRI and 18FDG-PET/CT scan were conducted. Follow-up pelvic examinations with cytology every 3 months and PET/CT at 3 and 12 months after completion of treatment were performed. Oncological outcomes and toxicities were assessed. Results: Twenty-one patients were analyzed: median age was 54 years (30–76 years); 19 patients had squamous cell histology and 2 had adenocarcinoma. Median follow-up was 32 months (8–56). The average dose administered to the gross tumor volume was 90.2 Gy (79.5–96.6), 79.8 Gy to all PET/MRI positive lymph nodes (63.0–89.7). No patents received BT; all but 3 received chemotherapy. Three-year local control was 100% (PFS = 90.4% and OS = 100%). There were 2 recurrences: a solitary skull lesion 18 months following CRT in a patient with mesonephric adenocarcinoma and a metastasis to a transposed ovary 15 months after CRT. No grade 3–4 toxicities were seen. Only 1 patient (4.7%) had late rectal grade II toxicity. Conclusions: Non-brachytherapy adaptive CRT for LACC is feasible. It allows for a significant dose escalation, thus providing better local control and likely increases PFS and OS at no cost of serious toxicity. Randomized studies comparing this approach to the current standard of care are needed.

Role of Transient Anions in Chemoradiation Therapy: Base Modifications, Cross-Links, and Cluster Damages Induced to Cisplatin-DNA Complexes by 1-20 eV Electrons.

The molecular mechanism of platinum-based drugs in concomitant chemoradiation therapy relies on enhancement of DNA damage in cancer cells, particularly that of detrimental clustered lesions and cross-links induced by the abundant low-energy electrons (LEEs) generated by ionizing radiation. We provide the complete 1-20 eV electron-energy dependence of the yields of all conformational LEE-induced lesions to biological DNA, when it binds to five molecules of the chemotherapeutic drug cisplatin. Recording at 1 eV intervals clearly show that the enhancement of all lesions is particularly intense at the energies of core-excited transient molecular anions (i.e., TMAs at 5, 6, and 10 eV). New TMAs are observed at 14 and 18 eV, only in yield functions of cisplatin-DNA complexes. Enhancements of all lesions by cisplatin are quantified over the 1-20 eV range, where maxima appear at 14 and 18 eV. The most detrimental lesions to cell survival exhibit the highest enhancements by factors of 2-3. Whereas no cluster lesions are induced by electrons of energy <5 eV in DNA, LEEs of any energy cause clustered damages in the complex. These results confirm the current notion that LEEs and TMAs play a dominant role in the molecular mechanism of platinum-drug chemoradiation therapy.

Effects of Exercise Training during Concomitant Chemoradiation Therapy in Head-and-Neck Cancer Patients: A Systematic Review.

Existing literature suggests that cancer survivors present with high rates of morbidity due to various treatment and disease-induced factors. Research has shown exercise to be beneficial in improving treatment outcomes and quality of life (QOL). This review was done to collect the current state of exercise-based interventions for cancer survivors in India. From the summarized data, exercise interventions were categorized into resistance training, aerobic training, and home-based walking program in head-and-neck cancers. A broad range of outcomes showed improvement in muscle strength, functional capacity, and QOL and hence supported the benefits of exercise-based interventions in this population. All the data retrieved, therefore, conclude that exercise-based interventions are safe, feasible, and beneficial in patients with head and neck cancer receiving chemoradiation therapy.

Impact of antineoplastic drugs on the nutritional status of older patients with cancer. Can the medical oncologist minimize the impact of these drugs on the nutrirional status of these patients?

Aging is associated, per se, with the loss of functional reserve of different organs and systems, a greater risk of vulnerability and frailty, sarcopenia and malnutrition, a reality that is extended to cancer patients. There are several factors that are associated with malnutrition in the elderly individual, such as the difficulty in regulating food intake, loss of appetite and anorexia associated with age, alteration of the senses of taste and smell, dysgeusia or economic problems. In the case of the cancer patient, other factors are added to these factors, such as: type of tumor; tumor stage; evolutionary moment of the disease; and baseline situation. Many therapeutic strategies used against the tumor, such as surgery, treatment with radiotherapy (concomitant or not with chemotherapy) and treatment with antitumor drugs influence also the risk of malnutrition. Thus, for example, concomitant chemo-radiation therapy in head and neck tumors, in lung cancer or in pelvic tumors represents a high nutritional risk antitumor therapy. Some of the repercussions of malnutrition in the oncological elderly are severe. Thus, for example, malnutrition in these individuals is associated with: worse survival; increased risk of early discontinuation of chemotherapy treatment; increased risk of chemotherapy toxicity; increased toxicity from other antitumor drugs; and increased risk of mortality during chemotherapy treatment. Taking this information into account, it is essential: to optimize the nutritional status in older patients with cancer prior to starting a systemic antitumor treatment; to carry out a nutritional follow-up throughout the treatment; and to offer early and intense management of malnutrition once it appears, with the purpose of minimizing the impact of antitumor drugs in older patients with cancer. Early management of malnutrition could improve drugs tolerance and increase the health-related quality of life in these patients.

Comparing efficacy of high-dose rate brachytherapy versus helical tomotherapy in the treatment of cervical cancer.

ObjectiveBoost radiation using brachytherapy (BT) is a standard treatment for local disease control in concomitant chemoradiation therapy (CCRT) for advanced cervical cancer. However, it is associated with gastrointestinal and genitourinary complications. Hence, this study investigates the feasibility of helical tomotherapy (HT) as an alternative to BT.MethodsMedical records of patients who underwent CCRT between 2000 and 2017 at a single institution were retrospectively reviewed. Patients with stage IIB–IVA cancers were selected based on the 2009 criteria of The International Federation of Gynaecology and Obstetrics. External beam radiation combined with chemotherapy was followed by either BT or HT. The propensity score matching of both groups was calculated using logistic regression analysis. Disease outcomes and treatment-related adverse events were compared between the 2 groups.ResultsThe matched population included 70 BT patients and 35 HT patients. The 5-year progression-free survival rates for BT and HT were 72.6% and 72.5%, respectively (p=0.721). There was no difference in the overall survival rate between the two groups (p=0.203). The presence of acute and chronic gastrointestinal complications was also similar between the groups (p=0.460 and p=0.563, respectively). The chronic genitourinary toxicities were also comparable (p=0.105).ConclusionsHT boost treatment showed comparable disease outcomes with those observed with conventional BT in patients with advanced cervical cancer. HT could be a complementary boost protocol as a single modality or hybrid with BT in selected patients. Further studies with longer follow-up periods are warranted to confirm long-term outcomes.

ACT-10 TREATMENT FOR GLIOBLASTOMA RECURRED AFTER CONCOMITANT CHEMORADIATION THERAPY WITH TEMOZOLOMIDE AND THEIR PROGNOSIS

There are few data about treatment for glioblastoma recurred after concomitant chemoradiation therapy with temozolomide (TMZ). We retrospectively examined treatment and prognosis of recurred glioblastoma patients who registered Kansai molecular diagnosis network for central nervous system tumors, and whose clinical information were available. One hundred and fifty-seven patients that were clinically diagnosed as recurrence between November 2007 and April 2019 were included. Their median age at primary diagnosis was 52 years old and median KPS was 80%. Proportion of methylated MGMT promoter was 43.3% (65 patients), and mutated IDH was 5.4% (8 patients). Median overall survival after recurrence (mSAR) was 8.2 months. One hundred and sixteen patients (73.9%) were received any anticancer treatment and their mSAR was 10.5m. Combination of TMZ and bevacizumab (Bev) were most frequently used for 33 patients, followed by Bev monotherapy for 17 patients, surgery + TMZ + Bev for 15 patients, surgery + TMZ for 12 patients, and TMZ monotherapy for ten. Their mSAR were 8.0m, 7.5m, 10.5m, 13.0m, and 8.0m, respectively. Using univariate analysis, MGMT promoter methylation (p=0.0007), TMZ (p=0.00933), surgery (p=0.0126), re-radiation (p=0.0367), and surgery+TMZ+Bev (p=0.0493) significantly affected prognosis. By multivariate analysis, MGMT promoter methylation, TMZ, and re-radiation were statistically significant (p=0.000138, 0.00161, 0.00403, respectively). These data showed that relatively young patients with good performance status would receive anti-cancer treatment beyond progression and MGMT promoter methylation might be one of prognostic factor for longer survival. In this cohort, re-radiation was performed for few patients and nitrosourea such as nimustine was almost not used. Further study would be needed whether these treatments have any positive effect or not.

Randomized Phase 2 Trial of a Novel Clonidine Mucoadhesive Buccal Tablet for the Amelioration of Oral Mucositis in Patients Treated With Concomitant Chemoradiation Therapy for Head and Neck Cancer

Oral mucositis (OM) is a frequent and painful sequela of concomitant chemoradiation (CRT) used for the treatment of head and neck cancer (HNC) for which there is no effective intervention. This randomized, placebo-controlled study evaluated the efficacy of a novel, mucoadhesive topical tablet formulation of clonidine in mitigating CRT-induced OM in patients with HNC. Patients with HNC undergoing adjuvant radiation therapy (60-66 Gy; 5 × 1.8-2.2 Gy/wk) with concomitant platinum-based chemotherapy received daily local clonidine at 50 μg (n = 56), 100 μg (n = 65), or placebo (n = 62) via a topical mucobuccal tablet starting 1 to 3 days before and continuing during treatment. The primary endpoint was the incidence of severe OM (severe OM [SOM], World Health Organization grade 3/4). SOM developed in 45% versus 60% (P = .06) of patients treated with clonidine compared with placebo and occurred for the first time at 60 Gy as opposed to 48 Gy (median; hazard ratio, 0.75 [95% confidence interval, 0.484-1.175], P = .21); median time to onset was 45 versus 36 days. Opioid analgesic use, mean patient-reported mouth and throat soreness, and CRT compliance were not significantly different between treatment arms. Adverse events were reported in 90.8% versus 98.4%, nausea in 49.6% versus 71.0%, dysphagia in 32.8% versus 48.4%, and reversible hypotension in 6.7% versus 1.6% of patients on clonidine versus placebo, respectively. Although the primary endpoint was not met, the positive trends of OM-associated outcomes suggest that the novel mucoadhesive tablet delivery of clonidine might favorably affect the course and severity of CRT-induced SOM and support further evaluation.

Prognostic value of post-induction chemotherapy 18F-FDG PET-CT in stage II/III non-small cell lung cancer before (chemo-) radiation.

IntroductionThe purpose of our present study was to assess the prognostic impact of FDG PET-CT after induction chemotherapy for patients with inoperable non-small-cell lung cancer (NSCLC).Material and methodsThis retrospective study included 50 patients with inoperable stage II/III NSCLC from January 2012 to July 2015. They were treated for curative intent with induction chemotherapy, followed by concomitant chemoradiation therapy or sequential radiation therapy. FDG PET-CT scans were acquired at initial staging (PET1) and after the last cycle of induction therapy (PET2). Five parameters were evaluated on both scans: SUVmax, SUVpeak, SUVmean, TLG, MTV, and their respective deltas. The prognostic value of each parameter for overall survival (OS) and progression-free survival (PFS) was evaluated with Cox proportional-hazards regression models.ResultsMedian follow-up was 19 months. PET1 parameters, clinical and histopathological data were not predictive of the outcome. TLG2 and ΔTLG were prognostic factors for OS. TLG2 was the only prognostic factor for PFS. For OS, log-rank test showed that there was a better prognosis for patients with TLG2< 69g (HR = 7.1, 95%CI 2.8–18, p = 0.002) and for patients with ΔTLG< -81% after induction therapy (HR = 3.8, 95%CI 1.5–9.6, p = 0.02). After 2 years, the survival rate was 89% for the patients with low TLG2 vs 52% for the others. We also evaluated a composite parameter considering both MTV2 and ΔSUVmax. Patients with MTV2> 23cc and ΔSUVmax> -55% had significantly shorter OS than the other patients (HR = 5.7, 95%CI 2.1–15.4, p< 0.01).ConclusionPost-induction FDG PET might be an added value to assess the patients’ prognosis in inoperable stage II/III NSCLC. TLG, ΔTLG as well as the association of MTV and ΔSUVmax seemed to be valuable parameters, more accurate than clinical, pathological or pretherapeutic imaging data.

Absolute cross sections for chemoradiation therapy: Damages to cisplatin-DNA complexes induced by 10 eV electrons.

In chemoradiation therapy, the synergy between the radiation and the chemotherapeutic agent (CA) can result in a super-additive treatment. A priori, this increased effectiveness could be estimated from model calculations, if absolute cross sections (ACSs) involved in cellular damage are substantially higher, when the CA binds to DNA. We measure ACSs for damages induced by 10 eV electrons, when DNA binds to the CA cisplatin as in chemotherapy. At this energy, DNA is damaged essentially by the decay of core-excited transient anions into bond-breaking channels. Films of cisplatin-DNA complexes of ratio 5:1 with thicknesses 10, 15, and 20 nm were irradiated in vacuum during 5-30 s. Conformation changes were quantified by electrophoresis and yields extrapolated from exposure-response curves. Base damages (BDs) were revealed and quantified by enzymatic treatment. The ACSs were generated from these yields by two mathematical models. For 3197 base-pair plasmid DNA, ACS for single strand breaks, double strand breaks (DSBs), crosslinks, non-DSB cluster damages, and total BDs is 71 ± 2, 9.3 ± 0.4, 10.1 ± 0.3, 8.2 ± 0.3, and 115 ± 2 ×10-15 cm2, respectively. These ACSs are higher than those of nonmodified DNA by factors of 1.6 ± 0.1, 2.2 ± 0.1, 1.3 ± 0.1, 1.3 ± 0.3, and 2.1 ± 0.4, respectively. Since LEEs are produced in large quantities by radiolysis and strongly interact with biomolecules, we expect such enhancements to produce substantial additional damages in the DNA of the nucleus of cancer cells during concomitant chemoradiation therapy. The increase damage appears sufficiently large to justify more elaborate simulations, which could provide a quantitative evaluation of molecular sensitization by Pt-CAs.

Subsequent thyroid disorders associated with treatment strategy in head and neck cancer patients: a nationwide cohort study

BackgroundWe investigated the risk of thyroid disorders, namely hypothyroidism, thyrotoxicosis and thyroiditis, in head and neck cancer patients undergoing multimodal treatment.MethodsA cohort study design using Taiwan’s National Health Insurance Research Database was used to assess head and neck cancer patients over 20 years old. The cohort was divided into one group who underwent primary tumor excision only (PTE) and another with additional neck dissection (PTE + ND). The tumor sites were stratified to estimate the tumor-site-specific risk of thyroid disorders. The effect of subsequent resurgery, radiotherapy (RT), chemotherapy (CT), and concomitant (CCRT) or sequential chemoradiation therapy (sequential CT+ RT) on the risk of thyroid disorders was explored.ResultsFor 1999–2012, 7460 patients who underwent PTE + ND and 3730 who underwent PTE were enrolled and followed-up until the end of 2013. There were 122 and 50 patients in the two groups, respectively, who developed thyroid disorders, with no statistical difference between the groups. Patients with hypopharyngeal, oropharyngeal, or laryngeal cancer in the PTE + ND group had a higher risk of thyroid disorders (adjusted HR: 1.50, 95% CI: 0.67–3.38) than those in the PTE group when adjusted for covariates and mortality. Patients who underwent subsequent RT (adjusted HR: 3.64, 95% CI: 1.05–2.77) and CCRT (adjusted HR: 1.70, 95% CI: 1.05–2.77) after PTE + ND had a significantly higher risk of thyroid disorders.ConclusionRT results in a major risk of subsequent thyroid disorders, and ND may exacerbate this effect. Physicians should monitor thyroid function from two years after treatment initiation, especially in patients who undergo ND and subsequent RT.

Contribution of Base Damages to the Molecular Radiosensitization Mechanism of Platinum Chemotherapeutic Drugs

AbstractThe measurement of clustered damages in Pt‐chemotherapeutic‐drugs‐DNA complexes induced by low‐energy (0‐30 eV) electrons (LEEs) may provide further understanding of the synergy mechanism in cancer treatment with concomitant chemoradiation therapy (CRT). Five‐monolayer films of Pt‐DNA complexes, containing cisplatin, carboplatin and oxaliplatin with ratio 5:1 were irradiated with mono‐energetic electrons of 10 eV, the most prominent energy for bond dissociation by LEE impact. Damages to plasmid DNA including crosslinks, SSBs, DSBs and the loss of the supercoiled configuration were analyzed by the electrophoresis. Base damages (BDs) occurring within two turns of DNA helix were detected by the treatment of E. coli base excision repair endonuclease (Nth and Fpg). The total DNA damages to Pt‐DNA complexes was found to be 350 ± 42, 296 ± 45 and 434 ± 46 ×10−15 electron−1molecule−1, respectively, while the percentages of BDs in this total were 56%, 54% and 60%, respectively. Compared to unmodified DNA, binding of Pt‐drugs to DNA increased BDs by factors of 1.9, 1.6 and 2.6, respectively, which partly resulted in significant enhancements of potentially lethal lesions (i. e., crosslinks, double strand breaks (DSBs) and non‐DSB cluster damages). These results reveal the significant role that LEEs play in the formation of clustered DNA damages related to BDs, which are expected to contribute to the higher efficacy of cancer treatment by CRT with the Pt‐drugs investigated.

Comparison of the prognostic value of F-18 FDG PET/CT metabolic parameters of primary tumors and MRI findings in patients with locally advanced cervical cancer treated with concurrent chemoradiotherapy

PurposeTo evaluate the effect of metabolic parameters of pretreatment primary tumor and regional lymph nodes with F-18-FDG PET/CT compared with MRI findings for the prognostic value and disease-free survival (DFS) in locally advanced cervical cancer. Material and MethodsFrom 2011 to 2016, 112 patients with a diagnosis of cervical cancer stages IB2-IVA treated with concomitant chemoradiation therapy with 3D intracavitary brachytherapy were analyzed. From this group, 50 patients who underwent pretreatment and posttreatment FDG PET/CT and MRI were enrolled. LRFFS, DFS, and overall survival were analyzed in comparison with FDG PET/CT and MRI data. Relationship between SUVmax data and DFS was also assessed. ResultsThe median followup was 21 months, and median age was 54 years. The estimated 5-year locoregional failure-free survival, DFS, and overall survival rates were 87.4%, 70%, and 81%, respectively. DFS was 59.5% in patients with nodal metastases in FDG PET/CT and 100% in node negative patients (p:0,017). DFS was 50% and 79.4% in MRI node-positive and in node-negative patients, respectively (p:0,260). In addition, the nodal SUVmax (p: 0.005) and posttreatment response in FDG PET-CT (p < 0.001) were significant prognostic factors for DFS. Furthermore, primary tumor volume in MRI (p:0,982), node positivity in MRI (p:0,301), and response in posttreatment MRI (p:0,26) are not significant prognostic factors for DFS. ConclusionAs a result, FDG PET/CT has higher accuracy than MRI in detecting lymph node metastasis, and tumor volume reduction on FDG PET/CT images was greater than that on MRI images after CCRT.