T1 N0 M0 Research Articles

Association Between Perioperative Chemotherapy and Survival in Men Undergoing Radical Resection for Primary Urethral Urothelial Carcinoma: An Analysis of the National Cancer Database.

The treatment landscape in invasive primary carcinoma of the urethra of urothelial histology closely aligns that of locally advanced urothelial carcinoma of the bladder. The survival benefit of perioperative chemotherapy for men undergoing radical surgery for primary urethral urothelial carcinoma (UUC) has not yet been well-elucidated. Using the National Cancer Database (NCDB), we identified men diagnosed with non-metastatic invasive UUC (T2-4 N0-2 M0) from 2004 to 2016 treated with radical extirpative surgery. We compared OS between patients who had received peri-operative neoadjuvant (NAC) or adjuvant (AC) chemotherapy and those who had not using Kaplan-Meier curves and multivariable Cox proportional hazards regression model. A total of 191 patients met inclusion criteria. 113 patients (59.2%) did not receive chemotherapy, while 39 (20.4%) and 39 (20.4%) received NAC and AC, respectively. Median follow-up was 28.0 months. Upon multivariable analysis, receipt of NAC (HR 0.50, 95% CI 0.28-0.91, P=.02) decreased the risk of all-cause mortality, while receipt of AC (HR 0.76, 95% CI 0.41-1.41) was not significantly associated with an OS benefit, as compared to no chemotherapy. Our study is the first to evaluate treatment specific outcomes in male patients with primary carcinoma of the urethra. We observed that neoadjuvant chemotherapy in men with UUC was associated with OS benefit. The utilization of NAC may improve survival, consistent with urothelial carcinoma of the bladder.

Prognostic value of matrix metalloproteinases and transforming growth factor – β in kidney cancer

Purpose of the study. The study's objective is to investigate the expression level of tissue and serum markers of oncogenesis and nephrofibrosis transforming growth factor beta (TGF‑β) and matrix metalloproteinase‑9 (MMP‑9) in patients operated for various stages of renal cell carcinoma.Materials and methods. The study prospectively included medical data of 60 patients with kidney cancer with T1–3N0M0 who received surgical treatment in the Clinic of Urologynamed after S. R. Mirotvortsev of the State Medical University from 2016 to 2019. The patients were divided into 3 groups: Group 1 included 20 patients who underwent laparoscopic kidney resection; Group 2–20 patients who underwent laparoscopic nephrectomy; Group 3–20 patients who underwent open nephrectomy. The control group consisted of 15 healthy volunteers without chronic kidney diseases. All patients signed an informed consent to participate in the study. All patients at the preoperative stage, in the early (7–10 days) and remote postoperative periods (after 1 and 2 years) were tested by solid‑phase ELISA on a StatFax 4200 analyzer using eBiosence and Cloud‑Clone Corp reagent kits for the serum concentration of oncogenesis markers MMP‑9 and TGF‑β1.Results. Initial increase of MMP‑9 concentration was detected in all groups of PCC patients compared to the control group (p ≤ 0.05). According to the results of ROC analysis, this indicator has high specificity and sensitivity for prognosis of preoperative stage of renal cell carcinoma. The sensitivity and specificity of MMP‑9 were 87.5 % and 62 %, respectively, and the diagnostically significant level of MMP‑9 was 958 ng/ml. A comprehensive analysis of the content of MMP‑9 and TGF‑β1 oncogenesis markers in serum and tumor cells revealed the correlation of these indicators in various biological objects.Conclusion. Markers of oncogenesis and nephrofibrosis TGF‑β1 and MMP‑9 provide an opportunity for non‑invasive monitoring of tumor progression and probability of metastasis in the clinical setting. Serum MMP‑9 are a reliable predictor of tumor growth. Serum TGF‑β1 concentration isn't a sufficiently reliable marker of tumor progression.

Lobectomy offers improved survival outcomes relative to segmentectomy for >2 but ≤4 cm non–small cell lung cancer tumors

ObjectiveThe objective was to compare overall survival (OS) between lobectomy and segmentectomy for patients with non–small cell lung cancers (NSCLCs) > 2 but ≤4 cm. MethodsThe National Cancer Database was queried to identify treatment-naïve patients with NSCLC tumors >2 but ≤4 cm. Eligible patients were diagnosed with pT1 or T2 N0 M0 disease, underwent lobectomy or segmentectomy, and received no adjuvant therapy. OS was compared using the Kaplan-Meier method, and the Cox proportional-hazards model was used to identify prognostic factors for death. Propensity score matching was performed to minimize the effects of potential confounders. ResultsIncluded were 32,792 patients: lobectomy (n = 31,353) and segmentectomy (n = 1439). Five-year OS was improved following lobectomy over segmentectomy for patients with >2 but ≤4 cm NSCLCs (62.3% vs 52.6%; P < .0001). Further stratification demonstrated improved 5-year OS following lobectomy over segmentectomy: >2 but ≤3 cm (64.9% vs 54.3%; P < .0001) and >3 but ≤4 cm (56.9% vs 47.6%; P = .0003). In patients with a Charlson-Deyo comorbidity index of 0, 5-year OS was greater following lobectomy for >2 but ≤4 cm tumors (67.1% vs 62.1%; P = .03). Further stratification demonstrated improved 5-year OS following lobectomy for patients with Charlson-Deyo comorbidity index of 0 and > 3 but ≤4 cm tumors (61.8% vs 54.6%; P = .02). Segmentectomy was prognostic for increased risk of death in the year 1 through 5 postoperative period (hazard ratio, 1.35; P < .0001). Five-year OS remained greater following lobectomy after propensity score matching (59.6% vs 52.7%; P = .02). ConclusionsLobectomy is associated with superior 5-year OS compared with segmentectomy and may be preferred for NSCLC tumors >2 but ≤4 cm when feasible.

“Watch and wait” strategy (active dynamic follow-up) in the management of rectal cancer patients with a complete clinical response

Background. Currently available chemoradiotherapy regimens for distal rectal cancer often ensure complete regression of the tumor and lymph node lesions. Therefore, patients with a complete clinical response can be managed with a “watch and wait” (ww) strategy.Objective: to evaluate 2-year overall and progression-free survival in patients with local and locally advanced rectal cancer with a complete clinical response who were managed with the ww strategy.Materials and methods. we performed retrospective analysis of treatment outcomes in patients with newly diagnosed, histologically verified, stage II–III, mrT1–2n1–2m0, T3–4n0–2m0 (within 0–10 cm of the anal verge), and mrT2n0m0 (within 0–5 cm of the anal verge) rectal cancer who had demonstrated complete clinical response to chemoradiotherapy. mandard tumor regression grade (TRg1–2) (assessed using magnetic resonance imaging of the pelvis) and palpatory/visual signs of residual tumor (assessed by digital examination and colonoscopy) were the main parameters evaluated. Overall and disease-free survival was analyzed using the Kaplan–meier method.Results. Twenty-seven patients with a complete clinical response were assigned to the ww group. mRI scans of the pelvis demonstrated that 5 patients (18.5 %) had TRg1, whereas 22 patients (81.5 %) had TRg2. T-downstaging after therapy was observed in 21 participants (77.7 %). n-downstaging was registered in all 14 patients (100 %) with regional lymph nodes affected. median follow-up time was 41 months (range: 25–114 months). Two individuals (7.4 %) developed progressive disease. Both of them had lengthy tumors as demonstrated by digital examination, colonoscopy, and magnetic resonance imaging; they immediately underwent radical surgery. The two-year overall and disease-free survival rates were 100 % and 92.6 %, respectively. Conclusion. The ww strategy with active dynamic follow-up is safe for the management of patients with local and locally advanced middle and lower rectal cancer, provided that inclusion/exclusion criteria are adhered to and patients are carefully followed-up in specialized centers.

Improved diagnostics of “concealed” metastases in patients with сТ1–2N0М0 oral squamous cell carcinoma

Introduction. Oral squamous cell carcinoma is associated with a high risk of regional metastasis even in early stages (T1–2N0M0). Morphological examination reveals concealed metastases in 20 % of removed clinically unaffected lymph nodes.Objective – to evaluate the effectiveness of flow cytometry for detection of concealed metastases in sentinel lymph nodes as an indication for cervical lymph node dissection in patients with stage сT1–2N0M0 oral squamous cell carcinoma.Materials and methods. This study included 27 patients, including 13 patients (48.1 %) with stage T1N0M0 cancer and 14 patients with stage T2N0M0 cancer (51.9 %). At the first stage, all participants underwent primary tumor removal and cervical lymph node dissection with sentinel lymph node examination. After mobilization, half of these lymph nodes was used for routine morphological examination followed by immunohistochemical examination, while the second half of them was analyzed using flow cytometry. Then we compared the results obtained.Results. We examined 46 removed sentinel lymph nodes from 27 patients. Conventional histological examination revealed 4 concealed metastases (8.7 %). Polymerase chain reaction allowed us to detect another 16 metastases (37.8 %). Levels I, II, and III lymph nodes were most frequently affected. Flow cytometry demonstrated that 20 % of patients with a &lt;4 mm invasion had concealed metastases, whereas patients with a 4 to 8 mm invasion had concealed metastases in 60 % of cases. Median follow-up time was 20.4 ± 11.7 months (range: 2.2 to 42.5 months; median 19.5 months). All participants were alive during this time. Seventeen out of 27 patients with stage T1–2N0M0 disease (63 %) were found to have concealed metastases, while the remaining ten patients (37 %) had no metastasis. One patient with stage T1N0M0 oral floor squamous cell carcinoma underwent the removal of the primary tumor and sentinel lymph node. Morphological examination and flow cytometry showed no metastatic lesions. After 14.8 months, the patient developed ipsilateral regional CN3 metastasis. The three-year progression-free survival rate was 94.7 ± 5.1 %.Conclusion. Highly sensible and rapid flow cytometry can become the method of choice in the diagnosis of metastases and deciding on cervical lymph node dissection in patients with cN0 disease. The study is still ongoing.

Treatment response in prostatic neoplastic lesions using CyberKnife (stereotactic body radiation therapy)

Objective: To evaluate the treatment response of CyberKnife stereotactic radiotherapy in patients with prostatic neoplastic lesions.Patients and methods: This prospective observational study was conducted at Radiology and Cyberknife Robotic Radiosurgery Department of Jinnah Post Graduate Medical Centre (JPMC), Karachi from 22nd June 2019 to 21st June 2020. Males with biopsy-proven prostatic adenocarcinoma with age 55 years or more having Gleason's score of 6 to 8, clinical stage of T1 to T2C, and prostate-specific antigen (PSA) of ≤30 ng/ml were consecutively enrolled. Detailed information regarding PSA concentration, Gleason score, T stage, risk group and ADT (Androgen Deprivation Therapy) usage were noted which were given to high risk patients only for 9 months. Drop in the PSA (biochemical marker) was assessed at baseline, at 3 months and 6 months follow-up.Results: The median age of the patients was 65 years. The overall median PSA level was 2.7 (0.86-7.3) ng/ml. Majority 49 (90.7%) patients presented with T2 N0 M0 TNM status while only 5 (9.3%) patients presented with T1 N0 M0 TNM status. There were 5 (9.3%) patients with high risk, 26 (48.1%) with intermediate risk, and 23 (42.6%) with low risk. ADT was received by 5 (9.3%) patients. The median PSA at baseline was 10.1 (6.9-18.1) ng/ml which significantly drops to 1.6 (0.8-3.6) ng/ml at 3rd months, and 0.4 (0.2-1.2) at 6th months (p-value &lt;0.01).Conclusion: The findings showed an adequate treatment response of CyberKnife stereotactic radiotherapy of patients with prostatic neoplastic lesions.

Relationship between the transcriptional activity of СT-genes and survival in colorectal cancer patients

Introduction. High incidence and mortality rates of colorectal cancer indicate an urgent need for the use of new highly specific diagnostic and prognostic molecular markers. In this aspect, cancer testis antigens (CTA s) are of particular interest.The aim of the study was to analyze the relationship between the transcriptional activity of CTA s and survival in colorectal cancer patients with metastases (T1–4N1–2M1–2) and without metastases (T1–3N0M0).Results. The relative expression of 16 genetic loci (MAGE-A1, MAGE-A2, MAGE-A3, MAGE-A4, MAGE-B1, MAGE-B2, GAGE-1, GAGE-3, GAGE-4, MAGE-C1, BAGE, XAGE3, NYESO1, SSX2, SCP1 and PRAME1) was determined by real-time PC R. In colorectal cancer patients having no metastases, the expression of SSX2 and PRAME1 genes was significantly higher and the expression of BAGE was significantly lower in colon tumor tissue than in normal tissue (p&lt;0.05). In colorectal cancer patient with metastases, the expression of GAGE1, SCP1 and PRAME1 genes was significantly higher and the expression of MAGEA2, MAGEB1, MAGEB2, GAGE4 and NY-ESO1 genes was significantly lower in colon tumor tissue than in normal tissue (p&lt;0.05). The expression of the GAGE1, BAGE, SSX2, MAGEA2, SCP1 and MAGEB1 genes was found to have a significant impact on the overall survival and the development of distant metastasis (p&lt;0.05).Conclusion. The data obtained are the basis for the formation of a panel of effective immunotherapeutic targets and prognostic markers for colorectal cancer patients with and without metastases.

Short-term efficacy and toxicity of total neoadjuvant chemotherapy in patients with resectable gastric cancer

Background. Currently, perioperative chemotherapy is the standard treatment option for resectable gastric cancer (GC ) at stages higher than T1. Preoperative chemotherapy was shown do not adversely affect the course of the postoperative period in gastric cancer patients. However, approximately 60 % of radically operated patients complete adjuvant chemotherapy. In this regard, the problem arises of postponing all courses of chemotherapy for operable gastric cancer to the preoperative period.The purpose of the study was to analyze short-term efficacy and toxicity of total neoadjuvant chemotherapy with FLOT regimen in patients with resectable gastric cancer.Material and Methods. Since 2020, the Research Cancer Institute of Tomsk National Research Medical Center has been conducting a pilot study, which included 25 patients with resectable gastric cancer (T2–4N0–2M0) who received 8 cycles of neoadjuvant chemotherapy with FLOT regimen followed by radical surgery (gastrectomy or distal subtotal resection of the stomach).Results. Preoperative chemotherapy was completed in 25 (100 %) patients. Side effects that occurred during chemotherapy did not require cancellation or interruption of treatment and reduction in the initial dose of drugs. The most common adverse events were emetogenic reactions (92 %), peripheral neuropathy (60 %), and neutropenia (48 %). All patients had no greater than grade II toxicity, which was reversed with standard maintenance therapy. Radical surgeries were performed 6 weeks after completion of chemotherapy cycle 8. There were no significant postoperative complications (grade III or higher according to the Clavien–Dindo scale) and deaths. The histological examination revealed pathological response of TG R2–3 grade in 21 (84%) patients. Downstaging in both T and N categories was found in 13 (52%) patients.Conclusion. Eight cycles of total neoadjuvant chemotherapy for resectable gastric cancer demonstrates high efficacy, moderate toxicity, and do not adversely affect the course of the perioperative period.

Comparative analysis of the use of technetium-99m labeled recombinant target molecules at doses of 1000 and 2000 μg for radionuclide diagnostics of HER2-positive breast cancer

Materials and methods. The study included 18 patients with breast cancer (T1–4N0–2M0) before systemic treatment: 10 — with HER2/neu overexpression; 8 — HER2/neu negative. In all cases, morphological, immunohistochemical studies, as well as FISH analysis of the primary tumor were performed. All patients underwent radionuclide studies (planar scintigraphy and SPECT of the chest) at 2, 4, 6 and 24 hours after injection of the «99mTc-DARPinG3» in dosages of 1000 and 2000 μg. Results. The half-life of the labeled protein from the blood was 3.5 hours for a dosage of 1000 μg; 3.8 h — for 2000 mcg. The organ with the highest absorption of «99mTc-DARPinG3» was the kidneys, regardless of the protein dose (0.10±0.02 and 0.10±0.03 mGy, respectively). The effective dose for 1000 μg was 0.011±0.001 mGy; for 2000 μg — 0.012±0.006. The liver absorption dose was significantly higher with 1000 μg of protein compared to 2000 μg (p&lt;0.005, Mann–Whitney U test). The tumor/background ratio was significantly higher at 2 and 4 hours after administration of the «99mTc-DARPinG3» in patients with HER2-positive tumors in 1000 and 2000 μg doses of protein (p&lt;0.005, Mann–Whitney U test). Conclusion. Clinical studies of the «99mTc-DARPinG3» in dosages of 1000 and 2000 μg demonstrated rapid elimination from the bloodstream and effective doses comparable to those obtained in the study with others alternative scaffold proteins labeled with various isotopes. An essential point of this work is the positive correlation of the protein dose with the accumulation of the compound in the liver, which is important component in diagnostic and allows to detect tumor sites in liver.

CLINICAL AND BIOLOGICAL CHARACTERISTICS OF T3N0M0 AND T4N0M0 BREAST CANCER

T3–4N0M0 breast cancer is rather rare among all breast cancers. The clinical features of these tumors and their biological nature are poorly studied in the scientific literature. In this study we showed that patients with T3N0M0 and T4N0M0 tumors revealed a number of common clinical features, comorbidities and biological characteristics of the tumor. At the same time carcinomas differed in their aggressiveness and the course of the disease. The history was shorter and the average tumor size was larger among patients from T3N0M0 group than in the T4N0M0 group, which indicates a higher tumor growth rate. Also, mean proliferation index ki-67 was higher in the T3N0M0 group than in the T4N0M0 group. The proportion of triple-negative and luminal B Her2‑negative biological subtypes was the largest in both the T3N0M0 and T4N0M0 groups. More than 50 % of women with T3–4N0M0 tumors had carcinomas with zero or low expression of hormonal receptors. Thus, such tumors were more aggressive and potentially highly sensitive to systemic chemotherapy in a significant proportion of patients with T3–4N0M0 breast cancer in our study.

Results of sole postoperative interstitial, high-dose-rate brachytherapy of T1–2 tongue tumours

PurposeTo describe the results of treating tongue cancer patients with single postoperative interstitial, high-dose-rate (HDR) brachytherapy (BT) after resection.MethodsBetween January 1998 and April 2019, 45 patients with squamous cell histology, stage T1–2N0–1M0 tongue tumours were treated by surgery followed by a single HDR BT in case of negative prognostic factors (close or positive surgical margin, lymphovascular and/or perineural invasion). The average dose was 29 Gy (range: 10–45 Gy) and rigid metal needles were used in 11 (24%) and flexible plastic catheters in 34 cases (76%). Survival parameters, toxicities and the prognostic factors influencing survival were analysed.ResultsDuring a mean follow-up of 103 months (range: 16–260 months) for surviving patients, the 10-year local and regional control (LC, RC), overall survival (OS), and disease-specific survival (DSS) probabilities were 85, 73, 34 and 63%, respectively. The incidence of local grade 1, 2 and 3 mucositis was 23, 73 and 4%, respectively. As a serious (grade 4), late side effect, soft tissue necrosis developed in 3 cases (7%). In a univariate analysis, there was a significant correlation between lymphovascular invasion and RC (p = 0.0118) as well as cervical recurrence and DSS (p < 0.0001).ConclusionSole postoperative HDR brachytherapy can be an effective method in case of negative prognostic factors in the treatment of early, resectable tongue tumours. Comparing the results of patients treated with postoperative BT to those who were managed with surgery or BT alone known from the literature, a slightly more favourable LC can be achieved with the combination therapy, demonstrating the potential compensating effect of BT on adverse prognostic factors, while the developing severe, grade 4 toxicity rate remains low.

Early-Stage Non-Small Cell Lung Cancer Stereotactic Body Radiation Therapy Outcomes in a Single Institution.

IntroductionThe gold standard treatment of stage I non-small cell lung cancer (NSCLC) is surgical resection. For medically inoperable patients, stereotactic body radiation therapy (SBRT) can provide comparable local control (LC) and overall survival (OS). The objectives of this study are to determine the three-year LC and OS for SBRT compared to early-stage NSCLC patients treated with alternative radiation modalities at our institution.Materials and methodsThis retrospective study included a total of 139 consecutive patients who were diagnosed with stage I (T1-2 N0 M0) NSCLC and treated with radiation therapy at our institution between 2015 and 2020. Patient demographics and clinical data were obtained from chart reviews. Treatment subgroups were: SBRT (48Gy/4 or 60Gy/8), hypofractionation (60Gy/15), conventional fractionation (60Gy/30 or 50Gy/20), and palliative radiation (20Gy/5, 30Gy/10, or 40Gy/15). Kaplan-Meier curves were plotted for LC and OS. We also performed Cox’s proportional hazard regression analysis.ResultsThe median patient age was 74 (range 52-91). The numbers of patients in each treatment subgroup were: SBRT (44), hypofractionation (78), conventional fractionation (8), and palliative (9). Differences in age, gender, and histopathological cell type between subgroups were not statistically significant. Metastatic progression was the most common outcome amongst treatment failures, followed by local recurrence and regional spread. Median post-treatment follow-up in months for each subgroup was: SBRT (20.2), hypofractionated (20.7), conventional fractionation (13.9), and palliative (14.4). Post-treatment three-year LC was found to be significantly better with SBRT (94%) versus hypofractionation (71%), conventional fractionation (80%), and palliative (71%). OS at three years were SBRT (67%), hypofractionation (59%), conventional fractionation (66%), and palliative (44%). As a whole, 72% (100/139) of patients had biopsy-proven NSCLC. Analysis showed biopsy status had no statistical significance with regards to LC or OS. Every 20 years of age had a 3.2x risk of death (95% CI: 1.425-7.268). Concerning the treatment modalities, there were significant differences for the hazard of death compared to SBRT: hypofractionation had 2.58x increased risk while palliative had 5.83x increased risk.The proportion of patients who experienced post-treatment radiation pneumonitis or dermatitis were: SBRT (7%, 2%), hypofractionation (8%, 3%), conventional fractionation (13%, 25%), and palliative (0%, 0%), respectively. No patients who experienced grade III or higher toxicities were observed as defined by Common Terminology Criteria for Adverse Events (CTCAE). ConclusionOur experience confirms SBRT can provide durable three-year local control with a comparable rate of post-treatment complications versus other radiation modalities for early-stage NSCLC. SBRT appears to be non-inferior to hypofractionation with regards to three-year LC.

A CASE OF INTRA-OPERATIVE INJURY TO LEFT MAIN PULMONARY ARTERY REPAIRED WITH A PERICARDIAL PATCH

Introduction: Patients with central lung tumours often undergo surgery, offering them a chance of cure. With central lung tumours, there is always the dreaded risk of injury to the left main pulmonary artery (PA) and rupture of the anterior segmental artery, known as the artery of sorrow. Case Presentation: A 75-year-old lady with a background of breast cancer presented to our cardiothoracic centre because computed tomography (CT) of the chest revealed a left lung lesion of 5 x 4 x 3.7 cm, in contact with oblique fissure, radiological staging T3 N2 M0, which was later shown to be highly avid on positron emission tomography (PET-CT). Resection via thoracotomy was done, due to dense attachment to PA, Left PA defect was noted after resection which was repaired with a pericardial patch with no post-operative complication. Discussion: In the event of tumours invading the PA, it is safe to divide the tumours completely and repair the PA using a patch if there are any complications. Conclusion: We performed a repair of the PA using a pericardial patch and reconstruction of the PA using a pericardial patch, and evidence shows that there is excellent long-term survival associated with this.

Long-Term Outcome in a Phase II Study of Regional Hyperthermia Added to Preoperative Radiochemotherapy in Locally Advanced and Recurrent Rectal Adenocarcinomas.

Simple SummaryRegional hyperthermia added to standard preoperative chemoradiotherapy for locally advanced and recurrent rectal cancer gives a high complete response rate and an improved long-term recurrence free survival.Hyperthermia was added to standard preoperative chemoradiation for rectal adenocarcinomas in a phase II study. Patients with T3-4 N0-2 M0 rectal cancer or local recurrences were included. Radiation dose was 54 Gy combined with capecitabine 825 mg/m2 × 2 daily and once weekly oxaliplatin 55 mg/m2. Regional hyperthermia aimed at 41.5–42.5 °C for 60 min combined with oxaliplatin infusion. Radical surgery with total or extended TME technique, was scheduled at 6–8 weeks after radiation. From April 2003 to April 2008, a total of 49 eligible patients were recruited. Median number of hyperthermia sessions were 5.4. A total of 47 out of 49 patients (96%) had the scheduled surgery, which was clinically radical in 44 patients. Complete tumour regression occurred in 29.8% of the patients who also exhibited statistically significantly better RFS and CSS. Rate of local recurrence alone at 10 years was 9.1%, distant metastases alone occurred in 25.6%, including local recurrences 40.4%. RFS for all patients was 54.8% after 5 years and CSS was 73.5%. Patients with T50 temperatures in tumours above median 39.9 °C had better RFS, 66.7% vs. 31.3%, p = 0.047, indicating a role of hyperthermia. Toxicity was acceptable.

Etude comparative entre l'irradiation prophylactique des ganglions et la radiothérapie du champ atteint dans le cancer de l'œsophage au stade précoce

INTRODUCTION : L’objectif de ce travail est d’analyser la faisabilité de l'irradiation prophylactique des ganglions dans le cancer de l’œsophage au stade précoce, évaluer l'effet curatif de la radiothérapie et déterminer les causes de l'échec du traitement. MATERIELS ET METHODES : Les données de 123 patients atteints d'un cancer de l'œsophage classé T1-2 N0-1 M0 ont été rétrospectivement étudiées. Les patients étaient répartis en deux groupes en fonction des modalités de la radiothérapie. Parmi eux, 102 ont bénéficié d’une radiothérapie du champ atteint et 21 ont bénéficié d’une irradiation prophylactique des ganglions. Une analyse comparative dans les deux groupes a été réalisée. RESULTATS : Chez les 123 patients, les taux de survie à un, trois et cinq ans étaient respectivement de 87,8%, 47,2% et 36,6%. Les taux de contrôle local à un, trois et cinq ans étaient de 89,4%, 67,5% et 48,8%, respectivement. Les taux de survie à un, trois et cinq ans chez 21 patients traités par une irradiation prophylactique des ganglions étaient de 90,5%, 47,6% et 42,9%, contre 86,3%, 49,0% et 35,2%, respectivement chez 102 patientes traités par la radiothérapie du champ atteint. Aucune différence significative n'a été trouvée entre les deux groupes (Chi2=0,290, p=0,588). Nos résultats indiquent que l’irradiation prophylactique des ganglions diminue significativement la survenue de métastases ganglionnaires (Chi2=5,778, p=0,016). CONCLUSION : La radiothérapie conformationnelle en 3D est l'un des meilleurs schémas thérapeutiques de radiothérapie dans le cancer de l’œsophage stade précoce. L'irradiation prophylactique des ganglions serait une option pour prévenir les métastases ganglionnaires régionales. La question de savoir si l’irradiation prophylactique des ganglions conduit à une amélioration de la survie globale, les résultats de la présente étude suggèrent des enquêtes plus approfondies.

A standard for hilar and intrapulmonary lymph node dissection and pathological examination in early non-small cell lung cancer.

BackgroundThere is considerable variation in the staging of lymph nodes (LNs) as part of tumor, node, metastasis (TNM) staging of non-small cell lung cancer (NSCLC). A new dissection and pathological examination standard for hilar and intrapulmonary LNs needs to be established for patients with early-stage T1–3N0M0 NSCLC.MethodsThis study involved 3,002 patients with T1–3N0M0 NSCLC who underwent radical lobectomy or total pneumonectomy in the thoracic departments of 11 Chinese institutions between January 1999 and October 2013. The Cox model was applied for univariate and multivariate analyses in the examination of station 10, 11 LN and station 12, 13, 14 LN. A hilar and intrapulmonary standard (HI standard) was then established based on univariate and multiple-factor analyses conducted using the Cox model.ResultsAmong the 3,002 patients enrolled in the study, 2,609 underwent at least one examination of station 10, 11 LN (A1), while 393 did not undergo examination of station 10, 11 LN (A0). The A0 and A1 groups had 5-year survival rates of 76% and 80%, respectively (P=0.018). Further, 1,764 patients underwent at least one examination of station 12, 13, 14 LN (B1), while 1,238 patients did not (B0). The B0 and B1 groups had 5-year survival rates of 77% and 82%, respectively (P=0.008). In total, 1,269 patients attained the HI standard (C1), and 1,733 did not (C0). The C0 and C1 groups had 5-year survival rates of 77% and 83%, respectively (P<0.001).ConclusionsThe HI standard can improve both the prognosis and survival rates of patients with T1–3N0M0 NSCLC. This will provide important guidance for pulmonary LN dissection and pathological examination in NSCLC cases.

A nomogram for predicting probability of low risk of MammaPrint results in women with clinically high-risk breast cancer

We aimed to develop a prediction MammaPrint (MMP) genomic risk assessment nomogram model for hormone-receptor positive (HR+) and human epidermal growth factor receptor-2 negative (HER2–) breast cancer and minimal axillary burden (N0-1) tumors using clinicopathological factors of patients who underwent an MMP test for decision making regarding adjuvant chemotherapy. A total of 409 T1-3 N0-1 M0 HR + and HER2– breast cancer patients whose MMP genomic risk results and clinicopathological factors were available from 2017 to 2020 were analyzed. With randomly selected 306 patients, we developed a nomogram for predicting a low-risk subgroup of MMP results and externally validated with remaining patients (n = 103). Multivariate analysis revealed that the age at diagnosis, progesterone receptor (PR) score, nuclear grade, and Ki-67 were significantly associated with MMP risk results. We developed an MMP low-risk predictive nomogram. With a cut off value at 5% and 95% probability of low-risk MMP, the nomogram accurately predicted the results with 100% positive predictive value (PPV) and negative predictive value respectively. When applied to cut-off value at 35%, the specificity and PPV was 95% and 86% respectively. The area under the receiver operating characteristic curve was 0.82 (95% confidence interval [CI] 0.77 to 0.87). When applied to the validation group, the nomogram was accurate with an area under the curve of 0.77 (95% CI 0.68 to 0.86). Our nomogram, which incorporates four traditional prognostic factors, i.e., age, PR, nuclear grade, and Ki-67, could predict the probability of obtaining a low MMP risk in a cohort of high clinical risk patients. This nomogram can aid the prompt selection of patients who does not need additional MMP testing.

Late-Stage Pancreatic Cancer Detected During High-Risk Individual Surveillance: A Systematic Review and Meta-Analysis

Identification and resection of successful targets, that is, T1 N0M0 pancreatic ductal adenocarcinoma (PDAC) and high-grade precursors during surveillance of high-risk individuals (HRIs) confers improved survival. Late-stage PDACs refer to T2-4 N0M0 and nodal or distant metastatic PDAC stages diagnosed during the follow-up phase of HRI surveillance. This study aimed to quantify late-stage PDACs during HRI surveillance and identify associated clinicoradiologic factors. A systematic search (PROSPERO:CRD42018117189) from Cochrane Library, Embase, Google Scholar, Medline, PubMed, Scopus, and Web of Science was last performed on April 18, 2021. Only original HRI surveillance manuscripts that specified follow-up strategies were included, and studies with only baseline information were excluded. Cumulative incidences of advanced neoplasia: high-grade precursors and all PDACs, and surveillance-detected/interval late-stage PDACs were calculated through random-effects model. Incidence of late-stage PDACs underwent metaregression to identify association with HRI clinicoradiologic features. Publication bias was assessed through the funnel plot and Egger's regression line. Thirteen original surveillance studies included 2169 HRIs followed over 7302.72 patient-years. Cumulative incidence of advanced neoplasia and late-stage PDACs was 3.3 (95% confidence interval [CI]: 0.6-7.4) and 1.7 (95% CI: 0.2-4.0) per 1000 patient-years, respectively. Late-stage PDACs lacked significant association with surveillance imaging, baseline pancreatic morphology, study location, genetic background, gender, or age. Limited information on diagnostic error, symptoms, timing of presentation, lesion site, and surveillance adherence precluded formal meta-analysis. A sizeable proportion of late-stage PDACs were detected during follow-up. Their incidence lacked association with baseline clinicoradiologic features. Further causal investigation of stage-based outcomes is warranted for overall improvement in HRI surveillance.

A Phase II Trial of Individualized Stereotactic Ablative Radiotherapy for Lung Tumors (iSABR)

Stereotactic ablative radiotherapy (SABR) is an effective treatment for lung tumors, but can result in toxicity such as chest wall pain and life-threatening damage to central lung structures. We hypothesized that while larger tumors require higher dose, small tumors up to 10cc in volume can be controlled with biologically effective dose < 100Gy. In this phase II single-arm trial, we tested the hypothesis that individualizing lung SABR dose and fractionation to tumor size, location, and histology would result in excellent local control with acceptable toxicity. The trial was conducted at two centers in the United States and Japan (NCT# redacted for blinded review).Patients in three groups were enrolled: initial diagnosis of non-small cell lung cancer (NSCLC), AJCC 7th edition stage T1-3 N0 M0 (group 1); new primary NSCLC with history of NSCLC, or multiple synchronously diagnosed NSCLCs (group 2); and lung metastases from NSCLC or another primary site (group 3). Up to four tumors could be treated with once-daily SABR. There were six dose/fractionation schedules used, depending on gross tumor volume (≤10cc, 10-30cc, > 30cc) and location (peripheral vs. central). Larger tumors received higher dose and central tumors generally received lower dose per fraction. Dose ranged from 25Gy in one fraction for 0-10cc peripheral tumors to 60Gy in 8 fractions for > 30cc central tumors. Colorectal cancer metastases were treated to higher dose, at least 50Gy in 4 fractions. The primary endpoint was per-group cumulative incidence of local recurrence at 1 year (recurrence of treated tumor within same lobe), with distant recurrence and death as competing risks. Treated tumor recurrence (recurrence with epicenter within 1cm of PTV) and toxicity were also analyzed.A total of 217 patients were enrolled from 2011-2018 (some patients were enrolled multiple times). Median age was 72, 59% were male, and 69% were current/former smokers. There were 240 treatment courses and 285 tumors treated (range 1-3 tumors per course). 211 tumors were peripheral and 74 were central. Tumor size distribution was: ≤10cc, 74%; 10-30cc, 19%; > 30cc, 7%. The most common dose was 25Gy in one fraction (158 tumors). Median follow-up was 30 months (range 2-95). Median overall survival was 57 months. Local recurrence data are currently being updated and will be presented at the meeting. The rate of grade 2 or higher pneumonitis was 16/217 (7%) and grade 3 or higher pneumonitis was 3/217 (1%). The rate of grade 2 or higher chest wall pain was 13/217 (6%). One patient had a grade 5 adverse event, developing pulmonary hemorrhage that was possibly related to radiotherapy, 17 months after treatment of a large central NSCLC.Individualized SABR to lung cancers resulted in excellent local control and favorable toxicity profile.

Single Institution Experience of Stereotactic Body Radiation Therapy in Non-small Cell Lung Cancer: Comparison of Two Dose Regimes and a Perspective on Ideal Dose Regimens.

IntroductionStereotactic body radiation therapy (SBRT) is an effective treatment for early-stage non-small cell lung cancer (NSCLC) patients who are either medically inoperable or who decline surgery. SBRT improves tumor control and overall survival (OS) in medically inoperable, early-stage, NSCLC patients. In this study, we investigated the effectiveness of two different SBRT doses commonly used and present our institutional experience.PurposeTo determine the clinical outcomes between two treatment regiments (50 Gray [Gy] vs. 55 Gy in five fractions) among Stage I NSCLC patients treated with SBRT at a state academic medical center.MethodsWe performed a retrospective analysis of 114 patients with Stage I (T1-2 N0 M0) NSCLC treated at a state academic medical center between October 2009 and April 2019. Survival analyses with treatment regimens of 50 Gy and 55 Gy in five fractions were conducted to detect any improvement in outcomes associated with the higher dose. The primary endpoints of this study included OS, local control (LC), and disease-free survival (DFS). Log-rank test and the Kaplan-Meier method were used to analyze the survival curves of the two treatment doses. The SPSS v.24.0 (IBM Corp., Armonk, NY, USA) was used for statistical analyses.ResultsThe 114 early-stage NSCLC patients (median age, 68 years; range 12 to 87 years) had a median follow-up of 25 months (range two to 86 months). The number of males (n = 72; 63.2 %) exceeded the number of females (n = 42; 36.8 %). The majority of patients in this study were Caucasians (n = 68; 59.6 %) and 46 patients were African Americans (40.4 %). Two-thirds of the patients (n = 76; 66.7 %) were treated with 50 Gy in five fractions, and 38 patients (33.3 %) with 55 Gy in five fractions. The one-, two-, and three-year OS and DFS rates were improved in the patients treated with 55 Gy [OS, 81.7 % vs. 72.8 %; 81.7 % vs. 58.9 %; 81.7 % vs. 46.7 % (p = 0.049)], [DFS, 69.7 % vs. 69.7 %; 61.9 % vs. 55.7 %; 61.9 % vs. 52.0 % (p = 0.842)], compared to those treated with 50 Gy. Adenocarcinoma was the most common histology in both groups (51.3 % and 68.4 %). Failure rates were elevated for the 50 Gy regimen [39 (34.2 %) vs. 12 (8.5 %)]. Three year control rates were (66.3 % vs. 96.6 %; p = 0.002) local control; (63.3 % vs. 94.4 %; p = 0.000) regional control; and (65.7 % vs. 97.1 %; p = 0.000) distant control, compared to those treated with 55 Gy.ConclusionEarly-stage NSCLC patients treated with SBRT 55 Gy in five fractions did better in terms of local control, overall survival, and disease-free survival rates compared to the 50 Gy in five fractions group.