IIIB Cancer Research Articles

A population-based analysis of the impact of 1 vs. 2 doses of mitomycin on patterns of failure of anal cancer patients treated with concurrent chemoradiotherapy

PurposeWe report the impact of 1 vs. 2 doses of mitomycin-C (MMC) based chemoradiation (CRT) on patterns of treatment failure and long-term patient outcomes in anal squamous cell carcinoma (ASCC) and the predictors for locoregional failure (LRF) and distant metastasis (DM). MethodsIn this population-based study, we identified all patients with anal cancer in our province treated radically with radiation and concurrent 5-Fluorouracil (5FU) and 1 vs. 2 doses of MMC between the years 2000-2019. The primary outcomes analyzed were locoregional recurrence (LRR), disease free survival (DFS), ASCC cancer-specific survival (ASCC-CSS) and overall survival (OS). Results451 patients were identified. 272 (60%) patients received 1 cycle of MMC (MMC1) and 179 (40%) received 2 cycles (MMC2) as part of the CRT regimen. The median follow-up was 57 (36-252) and 97 (38-239) months for MMC1 and MMC2, respectively. Cox Regression analysis showed stage IIIb and IIIc were associated with worse locoregional recurrence free survival (RFS) (HR=2.851, p=<0.001) and distant RFS (HR=3.391, p=<0.001). Similarly, stage IIIb and IIIc patients had poorer DFS (HR 3.439, p=<0.001), ASCC-SS (HR 3.729, p=<0.001) and OS (2.230, p=<0.001). The use of MMC2 showed a positive impact on improved ASCC-SS (HR 0.569, p=0.029) and distant RFS (HR 0.555, p=0.040) in patients with stage IIIb and IIIc. ConclusionsOur analysis showed that 1 vs. 2 cycles of MMC along with 5FU and radiation is associated with comparable treatment outcomes in general. However, in patients with stage IIIb and IIIc cancer, 2 doses of MMC were associated with improved ASCC-SS and distant DFS.

Surgical Outcomes in Non-Small Cell Lung Cancer with Distant Metastasis: The Prognostic Significance of Delayed Metastasis Diagnosis.

The diagnosis of distant metastasis on preoperative examinations for non-small cell lung cancer (NSCLC) can be challenging, leading to surgery for some patients with uncertain metastasis. This study evaluated the prognostic impact of delayed diagnosis of metastasis on patients who underwent upfront surgery. The study enrolled patients who underwent lobectomy or pneumonectomy for NSCLC between June 2010 and December 2017 and evaluated the presence of distant metastasis before surgery. Overall survival (OS) for patients with stage IV cancer was compared with that for patients without metastasis, and the prognostic factors were analyzed. Of 3046 patients (mean age, 63 years; 1770 men), 100 (3.3 %) had distant metastasis, diagnosed preoperatively in 1.4 % (42/3046) and postoperatively in 1.9 % (58/3046) of the patients. The two most common metastasis sites diagnosed after surgery were contralateral lung (22/58, 37.9 %) and ipsilateral pleura (16/58, 27.6 %). The OS (median, 42.7 months) for the patients with stage IV cancer diagnosed postoperatively was comparable with that for the patients with stage IIIB cancer (P = 0.865), whereas the OS (median OS, 91.7 months) for the patients with stage IV cancer diagnosed preoperatively was better than for the patients with stage IIIB cancer (P = 0.001). Among the patients with distant metastasis, squamous cell type (hazard ratio [HR], 3.15; P = 0.002) and systemic treatment for metastasis (HR, 2.42; P = 0.002) were independent predictors of worse OS. Among NSCLC patients undergoing upfront surgery, the OS for the patients with stage IV cancer diagnosed postoperatively was comparable with that for the patients with stage IIIB cancer. For patients with stage IV disease, squamous cell type and systemic treatment for metastasis were prognostic factors for poorer OS.

Efficacy and safety of mFOLFOX6 with apatinib as postoperative adjuvant chemotherapy in stage IIIB or IIIC colorectal cancer.

3613 Background: Antiangiogenic therapy has shown benefit in metastatic colorectal cancer. However, the role of apatinib in adjuvant treatment of stage IIIB and IIIC colorectal cancer remains unclear. Methods: Patients received modified FOLFOX6 once every 2 weeks for a 6-month period (control group) or modified FOLFOX6 for 6 months plus apatinib (500mg) once a day for a 12-month period (experimental group). Progression free survival (PFS), overal survival (OS) and treatment-related adverse events were evaluated in two groups. Results: 63 patients have been enrolled in this study. This trial reported a 3-year PFS of 74.2% for modified FOLFOX6 plus apatinib vs. 61.5% for modified FOLFOX6 ( P&lt; 0.05). 5-year OS was significantly improved in the experimental group compared with the control group (86.3% vs. 72.5%; P&lt; 0.05). The most common grade 3 adverse events were hypertension and hand–foot syndrome. No treatment-related grade 4 adverse events or treatment-related deaths were observed. Conclusions: Apatinib can prolong PFS and OS when added to adjuvant chemotherapy in resected stage IIIB and IIIC colorectal cancer. The toxicities associated with apatinib were generally acceptable. Clinical trial information: NCT03365765 .

Cisplatin-associated ototoxicity amongst cervical cancer patients: A prospective cohort study in south Africa.

Concurrent chemoradiotherapy using weekly cisplatin remains standard of care for locally advanced cervical cancer in Sub-Saharan Africa. While cisplatin remains a popular cancer chemotherapeutic, it has an irreversible ototoxic effect on patients' auditory system. However, there is a paucity of epidemiological information on its extent and severity during cervical cancer treatment. In a region with a high burden of cervical cancer, this has serious consequences for aural intervention and rehabilitation. Using a prospective cohort study design, 82 patients with incident cervical cancer, receiving weekly cisplatin chemotherapy (50 mg/m2 body surface) at a tertiary level hospital in KwaZulu-Natal Province of South Africa, underwent audiological assessments at various intervals. We describe the temporal impact of cisplatin exposure on hearing loss, its combined effect with HIV-infection, and estimate ototoxicity incidence in this cohort. The median age was 52 years with Stages IIB (45%) and IIIB (35.4%) cancers being most common. Complaints of reduced hearing sensitivity increased significantly (p<0.0001). Bilateral, asymmetrical sensorineural hearing loss, with greater effect in the extended high-frequency range, was evident. Cisplatin dosage was significantly associated with ototoxicity severity at one- (p = 0.017), three- (p = 0.010), and six-month (p = 0.015) post-treatment follow-up. HIV-seropositivity (53.7%) was significantly associated with NCI-CTCAE Grading Scale at three- (p = 0.022) and six-months (p = 0.023) post-treatment. Multiple Tobit regression revealed a cumulative dose effect bilaterally, after adjustment for age and HIV status, evident from 9000Hz and above in the right ear, while a plateau effect was observed at 250mg/m2 in the left ear. The incidence was ototoxicity was 98% at a cumulative dose of 150mg/m2. The findings of this epidemiologic study highlight the temporal course and severity of ototoxicity experienced by cervical cancer patients treated with cisplatin, with greater impact in HIV-positive subgroup, thus underscores the need for audiological monitoring and timely interventions in this cohort.

Abstract P4-07-60: Identification of Optimal Carboplatin Containing Regimen for Triple Negative Breast Cancer

Abstract Background: Current management for triple negative breast cancer (TNBC) involves chemotherapy and immunotherapy systemic treatments. TNBC treatment remains a challenge, with up to 40% of those treated using standard methods for stage I to III TNBC experiencing recurrence. Currently, the optimal carboplatin regimen for TNBC is yet to be defined. In our previous study, we identified an optimal carboplatin containing chemotherapy regimen that improved patient outcomes. In this study, we expanded the cohort as an extension of the previous prospective study to further verify these promising results. Patients and Methods: We performed a retrospective review of 37 TNBC patients who had &amp;lt; 10% estrogen and progesterone receptor positivity and were human epidermal growth factor receptor-2 (HER2) negative. This study was originally done in an adjuvant setting, but patients with locally advanced tumors received neoadjuvant chemotherapy. Patients received dose-dense Adriamycin, cyclophosphamide, and paclitaxel every two weeks for sixteen weeks. Adriamycin (60 mg/m^2) and cyclophosphamide (600 mg/m^2) were given intravenously every two weeks for four cycles, followed by paclitaxel (175 mg/m^2) every two weeks for four cycles. Carboplatin with an area under the curve of 6 was added to cycles two and four of paclitaxel. Last, we changed the parameters of continuing chemotherapy to allow platelet counts &amp;gt; 70,000 × 10^9. Only paclitaxel could be modified for neuropathy. Results: Of 37 patients enrolled in this trial, 35 patients survived without recurrence, one required a dose reduction in paclitaxel, and one has incomplete staging as grade is still pending. The two patients that did experience recurrence died. Of these two patients, the first had American Joint Committee on Cancer (AJCC) 7 stage IIIC cancer, and the second had two separate TNBCs at presentation – AJCC-7 IIB cancer of the right breast and AJCC-7 IIA cancer of the left breast. Under the AJCC-8 system, the first patient had AJCC-8 IIIB cancer, while the second patient had AJCC-8 IIIB cancer of the right and left breasts. These data suggest a completion rate of 97%, overall survival (OS) rates of 95% (AJCC-7 &amp; 8), and progression free survival (PFS) rates of 95% and 94% (AJCC-7 &amp; 8, respectively; Table 1). Additional stage-specific survival metrics and patient staging information are available in Table 1. Median follow-up in this study was 3.14 years. This is consistent with data from our previous study with significant PFS benefit over historic chemotherapy. All patients completed this regimen with no dose reductions of carboplatin and a 32% dose reduction in paclitaxel due to neuropathy. Toxicity was established in our previous study. The favourable toxicity profiling of the regimen allowed maximal tolerance for patients. Conclusion: Although administration of carboplatin with chemotherapy for TNBC is known to be beneficial, the ideal carboplatin containing regimen has not been identified because of concerns regarding toxicity and low completion rates. Here, an optimal carboplatin-containing regimen identified in our previous clinical trial led to 95% overall survival rates (AJCC-7 &amp; 8), 95% and 94% progression free survival rates (AJCC-7 &amp; 8, respectively), and a 97% completion rate for 37 TNBC patients. A limitation is that this is a small single center trial, and plans are underway to test this regimen with immunotherapy in a larger randomized control trial. Table 1: Patient Staging and Survival Metrics. Citation Format: Geoffrey J. Rempel, Claire S. Rim, Abdulkadir Hussein, Alina Bocicariu, Swati Kulkarni, Rasna Gupta, John Matthews, Amin Kay, Lisa Porter, Caroline Hamm. Identification of Optimal Carboplatin Containing Regimen for Triple Negative Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-07-60.

Effects of traditional Chinese medicine collaborative model (TCMCM) combined with adjuvant chemotherapy on IIIb and IIIc gastric cancer: a protocol for a randomized controlled trial

BackgroundMetastasis and/or recurrence can decrease the survival time of gastric cancer patients undergoing radical operation. Among them, those with stage IIIb and IIIc are especially at a high risk of metastasis and recurrence. The traditional Chinese medicine collaborative model (TCMCM) has been used in the treatment of cancer; however, its effects have not been systematically evaluated. This study is designed to evaluate whether TCMCM can decrease adverse effects after chemotherapy and reduce the recurrence and metastasis of stage IIIb and IIIc gastric cancer.Methods/designThis prospective, multicenter, randomized, open-label trial will recruit 260 patients with stage IIIb and IIIc gastric cancer who undergo radical surgery for D2 lymphadenectomy. The patients will be randomly assigned to receive usual adjuvant chemotherapy and TCMCM (intervention group) in a 1:1 ratio. Patients in the intervention group will receive an oral traditional Chinese formula, auricular acupressure, and acupoint therapy. All participants will receive usual adjuvant chemotherapy. The primary outcome is a 3-year disease-free survival rate. Secondary outcomes include quality of life, side effects caused by chemotherapy, and safety-related measures. Assessments will be performed during the screening period, at 4 and 8 cycles after adjuvant chemotherapy, and 9, 12, 18, 24, 30, and 36 months after randomization. Adverse events will be recorded. In addition, biological samples will be collected for mechanism analysis.DiscussionThis will be the first clinical trial to evaluate the effects of TCMCM on disease-free survival (DFS) and quality of life in patients with stage IIIb and IIIc gastric cancer. Our results may be used to standardize TCMCM. We will also perform a larger-scale clinical trial in the future.Trial registrationClinicalTrials.govNCT03607656. Registered on 1 July 2018. The final protocol version is V1.1.

Case Report on Complete Response and 5 year Survival of Non-Small Cell Lung Cancer IIIB Patient Treated with Integrative Medicine

Case Report on Complete Response and 5 year Survival of Non-Small Cell Lung Cancer IIIB Patient Treated with Integrative Medicine

Thoracoabdominal flap following modified radical mastectomy for locally advanced breast cancer: A case report

Introduction: For thoracic surgeons, extensive wall reconstruction post-resection in patients with locally advanced breast cancer (LABC) can pose considerable challenges. Targeting high-quality defect closures without significant morbidity, the operation can provide information about the thoracoabdominal flap in such patients after modified radical mastectomy that requires reconstructing the chest wall. Case Report: A 45-year-old woman presented with a lump in her right breast that had persisted for the past 10 months. With reference to her history, physical examination, and histopathological results, the patient was diagnosed with stage IIIB cancer (cT4bN0M0) in the right breast. The patient received 4 cycles of neoadjuvant chemotherapy with partial response before a planned modified radical mastectomy with a thoracoabdominal flap, accompanied by antibiotic therapy and analgesics. When wound care was provided and the thoracoabdominal flap evaluated on Day 2 after the operation, the flap area was warm and the same color as the surrounding skin, the capillary refill time was 3 s, and a blood test revealed red blood cells. Following a re-evaluation of the flap on Day 4 under sound conditions, the patient was discharged without complications on Day 5, and further treatment was planned. Conclusion: Using thoracoabdominal flaps in patients with LABC after modified radical mastectomy can yield good outcomes without complications.

Chemoradiation in Stage IIIB Cancer of the Uterine Cervix: A Review of the Zimbabwean Experience.

PURPOSECervical cancer remains the leading cause of cancer morbidity and mortality among Zimbabwean women. Many patients present with stage IIIB disease. Although definitive concurrent chemoradiation (CCRT) is the standard of care, there is a paucity of data on the effect(s) of this intervention in resource-constrained and high HIV-prevalence settings. We investigated the differences in CCRT initiation practices, tolerability, and outcomes in this group.PATIENTS AND METHODSWe performed a retrospective analysis of data from hospital records for patients with stage IIIB disease who were treated over a 2-year period at Parirenyatwa Group of Hospitals. Outcome measures were documented treatment-related adverse events and early clinical tumor response.RESULTSOne hundred twenty-eight (37%) of 346 patients received CCRT, and 65 (51%) of 128 patients were infected with HIV. CCRT was prescribed mostly in patients with less extensive disease—not involving lower third vaginal walls, minimal pelvic sidewall involvement (P = .002), and higher CD4+ count (P = .02). Eighteen percent of recorded adverse events were high grade (≥ 3). One patient did not complete treatment, and 68.5% achieved complete clinical tumor response at 3 months post-CCRT. A higher proportion of complete clinical tumor response was noted in those patients who were young, HIV uninfected, had less extensive disease, CD4+ of 500 cells/mm3 or greater, received four or more cycles of chemotherapy, received brachytherapy, and had no treatment breaks.CONCLUSIONThe study revealed that the use of CCRT to treat stage IIIB cervical cancer is low in Zimbabwe. Although several factors contribute, low CCRT uptake is mostly attributed to financial barriers. Well-selected patients tolerate the treatment and have good early clinical tumor response as expected. The role of CCRT for this patient group (and methods to make it available in resource-limited settings) must be further evaluated.

Synchronous Upper Intestinal Neurofibromas and Duodenal Periampullary Well-Differentiated Neuroendocrine Tumor Associated With Neurofibromatosis 1

Neurofibromatosis type I (NF1) is an autosomal dominant genetic disorder associated with characteristic skin findings, as well as a fourfold increase in risk of malignancy. NF1 patient malignancies commonly include the central and peripheral nervous system, but these patients are also at high risk of developing gastrointestinal (GI) tumors. While most often these GI tumors are benign upper GI neurofibromas; clinicians should have a high suspicion for malignant tumors, degeneration into a malignant peripheral nerve sheath tumor or less common associated malignancies such as well-differentiated neuroendocrine tumor (formerly carcinoid tumor), when patients present with multiple GI tumors. Our patient underwent a Whipple for symptomatic neurofibromas associated with NF1 and was unexpectedly discovered to have a metastatic duodenal well-differentiated neuroendocrine tumor. The patient is a 66-year-old man with NF1 who presented with hematemesis and was found to have large gastric neurofibromas and an ampullary neurofibroma based on endoscopy and radiological imaging. Another ostensive neurofibroma was noted distally. A pancreatoduodenectomy was performed. Pathological examination identified the neurofibromas but the tumor measuring 1.4cm and arising from the minor duodenal papilla was, in fact, a synchronous well-differentiated neuroendocrine tumor metastatic to regional lymph nodes, consistent with pT2 pN1, Stage IIIB cancer. NF1 patients with multiple GI tumors are at an increased risk for malignancy. Therefore, a high index of suspicion for malignancy in any patient with NF1 presenting with gastrointestinal symptoms has implications for a surgeon, warranting not only a further diagnostic investigation, but also an appropriate surgical intervention and sampling for nodal spread. Because of the possibility of a simultaneous cancer, it is crucial to assess all suspicious tumors even if the masses appear endoscopically benign.

Abstract CT237: A phase I study to assess the safety, tolerability, and immunogenicity of personalized neoantigen/cancer testis antigen nanovaccine (PVAC) for high-risk resected gastric cancer

Abstract Background: 35% of stage IIIB/C Gastric cancer patients will recurrent after D2 gastrectomy within one year. Mutation-derived epitopes (neoantigens) has been demonstrated to induce tumor cell specific immune responses controlling the tumor growth. Nanovaccine can increase antigen presentation efficiency and elicit potent antitumor T cell responses with robust therapeutic efficacy. We hypothesized that vaccination with neoantigens/cancer testis (CT) antigens could expand pre-existing and induce antigen-specific T-cells populations, favouring of tumor control enhancement. Here, we report the first-in-human application of this concept in gastric cancer. Methods: Patient-specific mutation-containing neoantigens were selected on the basis of tumour-specific mutations whole-exome sequencing (WES) and RNA sequencing. Cancer testis antigens were obtained according to immunohistochemical staining and HLA-binding affinity prediction. PVAC is an amphiphiles nanovaccine loaded with multiple personalized neoantigens/cancer testis antigens designed to induce antigen specific T cells and associated antitumor responses. PVAC will be administrated to stage IIIB/IIIC gastric carcinoma after six cycles of adjuvant chemotherapy (S-1/Oxaliplatin or S-1/docetaxel). Each patient received PVAC by subcutaneous injection on Days 1, 4, 8, 15, 22, 43, 64, 85, 169, administrated with the adjuvant montanide ISA 51 VG. Safety, immunogenicity and clinical efficacy will be evaluated. Results: 25 stage IIIB or IIIC gastric cancer patients were enrolled in this study. Mean age was 54.3 years old (range: 34-70), and ECOG performance scores were 0 or 1. Repeated dosing has been well tolerated with mild local discomfort and no DLTs. 10 of the 25 patients developed grade 1 local skin reactions with redness, swelling or subcutaneous indurations in the injection sites. Three patients were observed grade 2 local skin reactions in the injection sites. Four had grade 1 to 2 fever. No SAEs related to PVAC have been observed. Among median follow up time of 11.6 months (range: 7.5-24.0 months), only one patient had local recurrence at 10.5 months after surgery. The rest 24 patients remain disease free on study. Neoantigen specific T cell responses have been detected by IFN-γ Elispot from PBMCs. Conclusions: PVAC is a multiple neoantigens/CT antigens nanovaccine that personalizes tumor specific antigens and the individual patient's capacity to respond. Addition of PVAC may prolong progression-free survival (PFS) after the standard of care chemotherapy. Clinical trial information: ChiCTR1800017319. Citation Format: Qin Liu, Hanqing Qian, Jie Shao, Qiuping Xu, Huizi Sha, Yang Yang, Weifeng Wang, Lixia Yu, Baorui Liu, Jia Wei. A phase I study to assess the safety, tolerability, and immunogenicity of personalized neoantigen/cancer testis antigen nanovaccine (PVAC) for high-risk resected gastric cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT237.

Personalized neoantigen/cancer testis antigen nanovaccine (PVAC) mobilize specific therapeutic immunity for high-risk resected gastric cancer.

4535 Background: 35% of stage IIIB/C Gastric cancer patients will recurrent after D2 gastrectomy within one year. Mutation-derived epitopes (neoantigens) has been demonstrated to induce tumor cell specific immune responses controlling the tumor growth. Nanovaccine can increase antigen presentation efficiency and elicit potent antitumor T cell responses with robust therapeutic efficacy. We hypothesized that vaccination with neoantigens/cancer testis (CT) antigens could expand pre-existing and induce antigen-specific T-cells populations, favouring of tumor control enhancement. Here, we report the first-in-human application of this concept in gastric cancer. Methods: Patient-specific mutation-containing neoantigens were selected on the basis of tumour-specific mutations whole-exome sequencing (WES) and RNA sequencing. Cancer testis antigens were obtained according to immunohistochemical staining and HLA-binding affinity prediction. PVAC is an amphiphiles nanovaccine loaded with multiple personalized neoantigens/cancer testis antigens designed to induce antigen specific T cells and associated antitumor responses. PVAC will be administrated to stage IIIB/IIIC gastric carcinoma after six cycles of adjuvant chemotherapy (S-1/Oxaliplatin or S-1/docetaxel). Each patient received PVAC by subcutaneous injection on Days 1, 4, 8, 15, 22, 43, 64, 85, 169, administrated with the adjuvant montanide ISA 51 VG. Safety, immunogenicity and clinical efficacy will be evaluated. Results: 25 stage IIIB or IIIC gastric cancer patients were enrolled in this study. Mean age was 54.3 years old (range: 34-70), and ECOG performance scores were 0 or 1. Repeated dosing has been well tolerated with mild local discomfort and no DLTs. Three patients were observed grade 2 local skin reactions in the injection sites. No SAEs related to PVAC have been observed. Among median follow up time of 12.6 months (range: 8.5-25.0 months), only two patients had local recurrence at 24.0 months and 10.5 months after surgery, respectivelt. The rest 23 patients remain disease free on study. Neoantigen specific T cell responses have been detected by IFN-γ Elispot from PBMCs. Conclusions: PVAC is a multiple neoantigen/CT antigens nanovaccine that personalizes tumor specific antigens and the individual patient’s capacity to respond. Addition of PVAC may prolong progression-free survival (PFS) after the standard of care chemotherapy. Clinical trial information: ChiCTR1800017319 .

Impact of adjuvant radiotherapy on the survival of women with optimally resected stage III endometrial cancer in the era of modern radiotherapy: a retrospective study

BackgroundThe optimal adjuvant treatment for stage III endometrial cancer in the era of modern radiotherapy remains undefined. We investigated the benefit of adjuvant radiotherapy for women who underwent optimal resection for stage III endometrial cancer in the era of modern radiotherapy.MethodsWe retrospectively reviewed patients with endometrial cancer who were treated between 2010 and 2018. Adjuvant treatment included radiotherapy by modern radiotherapy techniques (intensity-modulated or volumetric modulated arc radiotherapy), chemotherapy, or both. Recurrence-free survival (RFS) and overall survival (OS) were calculated using the Kaplan-Meier method and analyzed via multivariate Cox proportional hazards models.ResultsOne hundred sixty-one patients were initially included (52, 9, and 100 with stages IIIA, IIIB, and IIIC cancer, respectively); 154 patients (96%) received adjuvant therapy. Such adjuvant treatment was associated with improved RFS (p = 0.014) and OS (p = 0.044) over surgery alone. Adjuvant radiotherapy by modern radiotherapy techniques led to low incidence of acute (25%) and chronic (7%) grade ≥ 2 gastrointestinal toxicity. On univariate analysis, non-endometrioid histology and grade 3 status were associated with higher risks of tumor recurrence and death, whereas adjuvant radiotherapy alone or in combination chemotherapy reduced their risks. On multivariate analysis, non-endometrioid histology was associated with increased recurrence (hazard ratio [HR], 2.95; p = 0.009), whereas adjuvant radiotherapy alone or with chemotherapy was associated with lower recurrence (HR, 0.62; p = 0.042). Patients > 60 years of age (p = 0.038) as well as those with endometrioid histology (p = 0.045), lymphovascular space invasion (p = 0.031), and ≥ 2 positive lymph nodes (p = 0.044) benefited most from adjuvant radiotherapy.ConclusionsModern adjuvant radiotherapy (intensity-modulated or volumetric modulated arc radiotherapy) alone or with chemotherapy should be considered for women with optimally resected stage III endometrial cancer.Trial registrationClinicalTrials.gov, NCT04251676. Registered 24 January 2020. Retrospectively registered.

Association Between Immune-Related Adverse Events and Recurrence-Free Survival Among Patients With Stage III Melanoma Randomized to Receive Pembrolizumab or Placebo

Whether immune-related adverse events (irAEs) indicate drug activity in patients treated with immune checkpoint inhibitors remains unknown. To investigate the association between irAEs and recurrence-free survival (RFS) in the double-blind EORTC 1325/KEYNOTE-054 clinical trial comparing pembrolizumab therapy and placebo for the treatment of patients with high-risk stage III melanoma. A total of 1019 adults with stage III melanoma were randomly assigned on a 1:1 ratio to receive treatment with pembrolizumab therapy or placebo. Eligible patients were adults 18 years and older with complete resection of cutaneous melanoma metastatic to lymph nodes, classified with stage IIIA (at least 1 micrometastasis measuring >1 mm in greatest diameter), IIIB, or IIIC (without in-transit metastasis) cancer. Patients were randomized from August 26, 2015, to November 14, 2016. The clinical cutoff for the data set was October 2, 2017. Analyses were then performed on the database, which was locked on November 28, 2017. Participants were scheduled to receive 200 mg of pembrolizumab or placebo every 3 weeks for a total of 18 doses for approximately 1 year or until disease recurrence, unacceptable toxic effects, major protocol violation, or withdrawal of consent. The association between irAEs and RFS was estimated using a Cox model adjusted for sex, age, and AJCC-7 stage, with a time-varying covariate that had a value of 0 before irAE onset and 1 after irAE onset. Of 1011 patients who began treatment with pembrolizumab therapy or placebo, 622 (61.5%) were men and 389 (38.5%) were women; 386 patients (38.2%) were aged 50 to 64 years, 377 (37.3%) were younger than 50 years, and 248 (24.5%) were 65 years and older. Consistent with the reported main analysis in the intent-to-treat population, RFS was longer in the pembrolizumab arm compared with the placebo arm (hazard ratio [HR], 0.56; 98.4% CI, 0.43-0.74) among patients who started treatment. The incidence of irAEs was 190 (37.4%) in the pembrolizumab arm (n = 509) and 45 (9.0%) in the placebo arm (n = 502); in each treatment group, the incidence was similar for men and women. The occurrence of an irAE was associated with a longer RFS in the pembrolizumab arm (HR, 0.61; 95% CI, 0.39-0.95; P = .03) in both men and women. However, in the placebo arm, this association was not significant. Compared with the placebo arm, the reduction in the hazard of recurrence or death in the pembrolizumab arm was greater after the onset of an irAE than without or before an irAE (HR, 0.37; 95% CI, 0.24-0.57 vs HR, 0.61; 95% CI, 0.49-0.77, respectively; P = .03). In this study, the occurrence of an irAE was associated with a longer RFS in the pembrolizumab arm. ClinicalTrials.gov identifier: NCT02362594; EudraCT identifier: 2014-004944-37.

High Doses to the Heart Are Associated with Reduced Overall Survival in Stage III Non-Small Cell Lung Cancer Patients Undergoing Radiation Therapy

To determine if radiation induced cardiac toxicity influences overall survival (OS) in stage III non-small cell lung cancer (NSCLC) patients undergoing radiation therapy (RT). A single institution database of 134 stage III NSCLC patients, treated with conventionally fractionated radiation therapy, was retrospectively analyzed in this study. The heart structure was contoured for each patient within a treatment planning system. Dose Volume Histogram (DVH) indices were computed from the cumulative whole heart DVH and were used together with patient specific characteristics in Multivariate Cox Regression model. A family of models, each using a single DVH index and prescription dose, patient age, mean lung dose, lungV20, tumor site, tumor laterality and disease stage were examined to find dosimetric indices which were most predictive for OS. Akaike Information Criterion was used in each model to find significant predictors for the OS. Subsequently, each heart was digitally subdivided into four parts along sup-inf and left-right axes. The same analysis was repeated using cumulative DVHs in each sub-part separately. 60% of patients presented with stage IIIA and 40% with stage IIIB cancer. Doses prescribed were 61.9±6.8Gy in 2Gy fractions, and 77% of patients also received chemotherapy. The mean time to the last follow-up was 1.5 years, with a range of 0.13 to 6.8 years. The mean age was 70.5 years with a range of 42 to 91 years. High doses to the heart were found to be significant predictors for OS, specifically: V%_55Gy (p=0.01) and V%_60Gy (p=0.04), where V%_D is the percentage of the volume which received dose D, or greater. The hazard ratio (HR) associated with heart irradiation was approximately 1.05 per 1% of whole heart volume irradiated to the dose 55Gy, or greater. Three patient characteristics were also found to be predictive for OS in all models: cancer stage (IIIA/IIIB, HR=1.7, p=0.02), chemotherapy (HR=0.34, p<0.01) and age before RT (HR=1.03/year, p=0.02). The analysis of digitally subdivided heart structures showed that V%_55Gy (p=0.01) and V%_60Gy (p=0.02) in the right-superior portion of the heart were significant predictors for the OS, while doses to the remaining three segments of the heart were not predictive. High doses to the heart reduce overall survival in stage III NSCLC patients treated with radiation therapy. High doses to the right-superior portion of the heart appear to be primarily responsible for the decrease in OS.

Activity of manganese superoxide dismutase (MnSOD) as a predictor of radiation therapy outcome in patients with stage IIIB squamous cell carcinoma cervical cancer

BACKGROUND Radiation is a standard therapy for cervical cancer. Unfortunately, not all patients undergoing radiation achieve a complete response. Previous studies have shown that manganese superoxide dismutase (MnSOD) acts against free radicals generated by radiation in cancer cells thus predicting worse outcome in radiation therapy. This study was aimed to assess and evaluate whether MnSOD activity can be used as a predictor of radiation therapy responses in patients with stage IIIB squamous cell carcinoma (SCC).&#x0D; METHODS A comparative cross-sectional study was conducted in the Gynecology Oncology Division, Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo Hospital, Jakarta. The database from previous research was analyzed to identify positive and negative response samples. Measurement of MnSOD activity was done using spectrophotometry based on the McCord and Fridovich method using RanSOD® kit. The comparative data were obtained and then analyzed.&#x0D; RESULTS Among 76 samples, 49 (61.8%) patients had positive responses and 27 (38.2%) had negative responses. It is shown in this study that higher MnSOD activity is related to worse radiotherapy outcome in stage IIIB cancer patients. The relative risk value of having a worse outcome with high MnSOD activity is 1.849 (1.075–3.178, 95% CI).&#x0D; CONCLUSIONS Stage IIIB squamous cell carcinoma patients with high MnSOD activity are at higher risk of having a negative radiation therapy response compared with patients without high MnSOD activity.

Feasibility of an eight-week outpatient-based pulmonary rehabilitation program for advanced lung cancer patients undergoing cytotoxic chemotherapy in Korea.

The scientific evidence supporting pulmonary rehabilitation (PR) for lung cancer patients undergoing cytotoxic chemotherapy is accumulating; however, the feasibility of outpatient‐based PR in these patients has not yet been evaluated in Korea. We conducted an eight‐week outpatient‐based PR feasibility study in a tertiary referral hospital setting. Patients with advanced lung cancer (non‐small cell lung cancer IIIB–IV and small‐cell lung cancer extensive disease) scheduled to undergo first‐line cytotoxic chemotherapy underwent PR consisting of 60‐minute sessions twice a week under the guidance and supervision of a physical therapist, for a total of eight weeks. Feasibility was assessed based on completion of the PR program. In total, 12 patients (median age 68 years) were enrolled; 11 (91.7%) were male with a history of smoking. Among these 12 patients, 9 (75%) completed the eight‐week outpatient‐based PR program. Three patients could not complete the PR program: two were unwilling and one died from complications of lung cancer. This study showed a 75% completion rate of an eight‐week outpatient‐based PR program for advanced lung cancer patients undergoing cytotoxic chemotherapy, which supports its feasibility.

Measurement of Nucleic Acid Metabolizing Enzymes in Stage III Colorectal Cancer Adds Precision to Adjuvant Fluorouracil and Leucovorin Therapy

1. Abstract 1.1. <span style=font-size:10.0pt;mso-fareast-font-family: ms= mincho=>Background <span style=font-size:10.0pt;mso-fareast-font-family: ms= mincho=>: Recurrence of colorectal cancer has been shown to be inhibited by adjuvant chemotherapy. To achieve effective adjuvant chemotherapy, a target molecule is necessary . Therefore, we performed a prospective clinical trial to determine the relationship between adjuvant chemotherapy outcomes and prognostic factors in colorectal cancer based on nucleic acid metabolizing enzyme levels. 1.2. Methods: A total of 147 patients with stage IIIA, IIIB, and IIIC cancer were selected for adjuvant chemotherapy. We analyzed Disease-Free Survival (DFS) as the primary endpoint and Overall Survival (OS) as the secondary endpoint in relation to the Thymidylate Synthase (TS) and Dihydropyrimidine Dehydrogenase (DPD) levels as measured by enzyme-linked immunosorbent assay. According <span style=letter-spacing: -.15pt>to the levels of the mean preliminary TS of 21.0 ng/mg protein and DPD of 115 ng/mg protein, the patients were divided into 4 groups. They were then administered postoperative adjuvant chemotherapy that primarily included fluorouracil and Leucovorin (FL) or Uracil/Tegafur (UFT) and Leucovorin (UZEL) for 6 months. 1.3. Results: The 5-year DFS in advanced stage III cancer was 63.9%. A significant difference was observed between the LL (low TS and low DPD levels) and HL (high TS and low DPD levels) groups and the LH (low TS and high DPD levels) and HH (high TS and high DPD levels) groups. Multivariate<span style=letter-spacing: -.5pt> analysis revealed a significant difference<span style=letter-spacing: -.1pt> in stage, TS level, and TS and DPD levels. The OS was 79.6% for all the groups. A significant difference was observed between the LL, LH, and HL groups and the HH groups. Multivariate analysis revealed a significant difference<span style=letter-spacing: -.5pt> in the stage, age, TS level, and<span style=letter-spacing: -.55pt> TS and DPD levels. <span style=font-size:10.0pt;letter-spacing: -.15pt>1.4. Conclusions: Measurement of the TS and DPD levels of a primary colorectal cancer lesion as target molecules may be helpful for achieving an effective postoperative adjuvant chemotherapy. TS and DPD can potentially serve as more accurate predictors of OS than age and cancer stage. 2. Keywords: Adjuvant Chemotherapy; Colorectal Cancer; Metabolizing <span style=font-size: 10.0pt;mso-fareast-font-family: ms= mincho=> <span style=font-size: 10.0pt>Enzyme; Precision Medicine

Can low‐dose radiotherapy volumes be one of the contributing factors to early relapses in lung cancer patients?

AbstractObjectiveSeveral studies have shown that low‐dose radiotherapy (RT) might increase tumor invasion and metastases. Whereas multiple RT fields that increase low‐dose RT areas are often used to prevent damage to organs at risk. We carried out a clinical trial with the concern that low‐dose RT sites could increase invasions or metastases when multiple sites were used.MethodsA clinical retrospective study was carried out on 50 lung cancer patients with stage II–IIIB cancer, who underwent RT and/or chemotherapy, had Eastern Cooperative Oncology Group performances 1–3, were aged 45–87 years, and without metastases. RT was carried out for 5 days with 180–200 cGy fractions per day with a total dose of 54–66 Gy. The radiation dose volume areas V5, V10, V20, V40, V50, and V60 of lung were calculated and analyzed by Mann–Whitney U‐test and L par test on disease‐free and overall survival statistically.ResultsIt was determined that V5, V10, and V20, which constitute the low RT dose areas of the lung, positively affected the recurrence‐free and overall survival minimally according to r correlation values.ConclusionLow‐dose RT volumes were positively affected minimally by recurrence‐free survival and overall survival in the present study. The effects of low‐dose radiation must be evaluated more clearly in studies.

Computed Tomography Liver Spleen Ratio as Predictive Marker of Liver Injury among Adult Filipina Early Breast Cancer Receiving Neoadjuvant Therapy from 2010-2016: A Six-Year Retrospective Study

There is no way to predict development of liver injury in early breast cancer patients during neoadjuvant treatment. It is our aim to determine such by determining Computed tomography liver spleen ratio (LS ratio) and comparing it to liver function test. Methods: Retrospective review for Stage I-III invasive breast cancer. Computed tomography LS ratio was reviewed by one radiologist. LS ratio cut off values were tested of their accuracy wherein computed AUC of &gt; 0.70 is considered valid predictive markers. Results: Thirty-five patients were seen with median age of 54, 57% had stage IIIB cancer. Patients’ average LS ratio 1.10±0.30 at the start, thenit slightly increased towards the end of the treatment (1.13±0.32). SGPT (37.43 to 35.09, p=0.479) changed from start to end. Liver spleen ratio significantly correlated with SGPT (r= -0.541, p=0.001). At end of treatment, LS ratio is correlated with SGPT (r = -0.464, p=0.005). It has higher sensitivity at start of treatment 100%, cut off 0.52, while end of treatment cut off was 0.87 has higher sensitivity (100%) in predicting liver injury. Liver Spleen ratio at end of treatment showed higher accuracy (AUC =0.597) indicating the LS ratio can be utilized as marker for predicting liver injury. Conclusion: End of treatment, liver injury was seen in those receiving anthracycline- based regimen. Liver spleen ratio is significantly correlated with SGPT. Liver spleen ratio at end of treatment showed higher accuracy indicating the LS ratio be utilized as marker for predicting liver injury