Locoregional Tumor Control Research Articles

Lateral temporal bone resection for cutaneous carcinomas of the external auditory canal and peri-auricular region.

To evaluate the outcomes for patients after lateral temporal bone resection surgery for cutaneous squamous cell carcinoma and basal cell carcinoma, and to ascertain predictors of survival and treatment failure. A retrospective review was conducted of the medical records for all patients who underwent lateral temporal bone resection for cutaneous squamous cell carcinoma or basal cell carcinoma between 2007 and 2019 in Western Australia. Thirty-seven patients underwent lateral temporal bone resection surgery. Median follow-up duration was 22 months. Twenty-five patients had squamous cell carcinoma and 12 had basal cell carcinoma. The overall survival rate at two years for patients with squamous cell carcinoma was 68.5 per cent. Pre-operative facial nerve involvement (determined via clinical or radiological evidence) was identified as a predictor of mortality (hazard ratio = 3.411, p = 0.006), with all patients dying before two years post-operatively. Locoregional tumour control was achieved in 81 per cent of cases (n = 30). Lateral temporal bone resection offers acceptable local control rates and survival outcomes. Caution should be used in offering this surgery to patients with clinical or radiological evidence of facial nerve involvement because of the relatively poorer survival outcomes in this subgroup.

Critères qualité de la résection chirurgicale et chirurgie d’épargne parenchymateuse: Quality criteria for lung cancer surgery and lung parenchymal preservation

The quality of surgical treatment for non-small cell lung cancer (NSCLC), is based on oncological recommendations and should guide our daily surgical practice and clinical research, at a time when alternative ablative techniques are emerging, as well as multimodal medical care, with or without surgery. Quality criteria to perform this type of surgery can be found at different levels: quality of the surgical indication confirmed by multidisciplinary team (MDT) meeting, quality of resection linked with the surgeon’s expertise, quality of perioperative care, quality of the pathologist’s analysis and quality of long-term follow-up. Only the centres certified for cancer thoracic surgery are authorised to perform this type of surgery. For a patient with localised resectable NSCLC, the recommended treatment remains complete anatomical surgical resection associated with radical lymphadenectomy. This surgical procedure allows optimal locoregional tumour control and precise pathological staging (pTNM), offering a prognostic value. It is essential to determine the adjuvant strategy. In the absence of respiratory failure, lobectomy remains the gold standard for resection. However, recent studies have shown that segmentectomy may become a favoured option for resection of smaller tumours (2 centimetres of less) without lymph node invasion (N0). In any extent of parenchymal resection, the lymphadenectomy has to be identical and follow international recommendations. The ultimate objective of this surgery is patients’ long-term survival, directly correlated with all quality criteria, particularly complete resection (R0).© 2021 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Intraoperative Cryotherapy in the Treatment of Metastatic Renal Cell Carcinoma of the Bone.

Osseous metastases in renal cell carcinoma (RCC) are a heterogeneous mix of cells with hypervascular and rapidly destructive properties that frequently exhibit resistance to both radiation and chemotherapy. Despite this, some patients with isolated and oligometastatic disease have the potential to be cured. Regardless, aggressive metastatic control is critical to minimizing morbidity and mortality for all patients with metastatic RCC. Percutaneous cryoprobes were developed as a minimally invasive technique for both pain relief and tumor control. However, there is little evidence describing an alternative use of this technology in the operating room to assist with open tumor resections, and no formal role for its use in orthopedics exists. Therefore, the authors added this modality to their intraoperative treatment of osseous RCC to investigate whether it would influence their ability to obtain local metastatic control. The authors performed a retrospective chart review of prospectively obtained data to evaluate the role of intraoperative cryotherapy in the treatment of osseous RCC. From 2004 to 2017, cryotherapy was used in 43 procedures, alleviating the need for additional radiation 84% (36 of 43) of the time. Local tumor control was achieved in 100% (43 of 43) of cases. There were 2 wound-related complications and 1 pathologic fracture. Despite the study's limitations, the authors believe that cryotherapy contributed to the reliability and reproducibility of their intralesional resections. Given the palliative, and potentially curative, opportunities afforded by complete locoregional tumor control, the authors support further investigation into the use of intraoperative cryotherapy to treat osseous metastases secondary to RCC. [Orthopedics. 2021;44(5):e645-e652.].

Rare lung cancers—Primary pulmonary leiomyosarcoma: A case report

SummaryPrimary pulmonary sarcomas (PPS) are rare mesenchymal lung cancers, which do not present clinically or radiological different to lung carcinomas. Definite PPS diagnosis can only be made by histological analysis and detailed staging examinations in order to exclude a secondary pulmonary malignancy such as metastatic soft tissue sarcoma or another solid tumour. Here we present the case of a 66-year-old woman with a pulmonary mass infiltrating the diaphragm and the mediastinal adipose tissue, which was identified as leiomyosarcoma. The patient received curative surgery with complete tumour R0 resection. The prognosis of PPS is defined by tumour size, lymph node status and histological grading. Surgery is the mainstay of therapy and there is no definitive indication for adjuvant therapy for R0-resected and lymph-node-negative patients like in our case. However, multimodal therapy approaches such as (neo)adjuvant chemo- and radiotherapy can contribute to improving locoregional tumour control, which is the most important prognostic factor. With our case report we want to raise awareness for pulmonary sarcomas as a relevant proportion of rare lung cancers which have to be kept in mind during the differential diagnosis. Moreover, we aim to discuss the complex and individual interdisciplinary management.

Oct4 confers stemness and radioresistance to head and neck squamous cell carcinoma by regulating the homologous recombination factors PSMC3IP and RAD54L

Head and neck squamous cell carcinoma (HNSCC) is often being diagnosed at an advanced stage, conferring a poor prognosis. The probability of local tumor control after radiotherapy depends on the eradication of cancer stem cells (CSCs) with activated DNA repair. This study provides evidence that the CSC-related transcription factor Oct4 contributes to HNSCC radioresistance by regulating DNA damage response and the CSC phenotype. Knockdown of Oct4 A isoform reduced self-renewal capacity in HNSCC and led to partial tumor cell radiosensitization caused by transcriptional downregulation of the cell cycle checkpoint kinases CHK1 and WEE1 and homologous recombination (HR) repair genes PSMC3IP and RAD54L. Besides, PARP inhibition with Olaparib selectively radiosensitized Oct4 A knockout, but not wild-type HNSCC cells. This finding links Oct4 A to the HR-mediated DNA repair mechanisms. In turn, knockdown of PSMC3IP and RAD54L reduced the HNSCC self-renewal capacity and clonogenic cell survival after irradiation, suggesting the interplay between DNA repair and the CSC phenotype. Similar to the effect of Oct4 knockdown, overexpression of Oct4 also resulted in significant HNSCC radiosensitization and increased DNA damage, suggesting that Oct4-dependent regulation of DNA repair depends on its fine-tuned expression. In line with this observation, HNSCC patients with high and low nuclear Oct4 expression at the invasive tumor front exhibited better loco-regional tumor control after postoperative radio(chemo)therapy compared to the intermediate expression subgroup. Thus, we found that the Oct4-driven transcriptional program plays a critical role in regulating HNSCC radioresistance, and a combination of radiotherapy with PARP inhibitors may induce synthetic lethality in Oct4-deregulated tumors.

Patterns of care, toxicity and outcome in the treatment of salivary gland carcinomas: long-term experience from a tertiary cancer center

BackgroundSalivary gland carcinomas (SGC) cover a heterogeneous group of malignancies with a lack of data of high-level evidence.MethodsClinical data of 127 patients treated for SGC at a university cancer center between 2002 and 2017 were analyzed retrospectively. The association of clinicopathological characteristics, treatment modalities, adverse events, and outcome was assessed.ResultsPatients received surgery (n = 65), surgery followed by (chemo-)radiotherapy (n = 56), or primary (chemo-)radiotherapy (n = 6). Injury to the cranial nerves or their branches was the most frequent surgical complication affecting 40 patients (33.1%). Ten year overall and progression-free survival rates were 73.2% and 65.4%, respectively. Parotid tumor site, advanced tumor, and positive nodal stage remained independent negative prognostic factors for overall survival, loco-regional and distant tumor control in multivariate analysis.ConclusionsOptimizing treatment strategies for SGC, depending on distinct clinicopathological factors, remains challenging due to the low incidence rates of the disease.

Treatment of genitourinary carcinoma in dogs using nonsteroidal anti-inflammatory drugs, mitoxantrone, and radiation therapy: A retrospective study.

BackgroundLocoregional tumor control and prolonged survival for dogs with genitourinary carcinoma (CGUC) reportedly are achievable using treatment with radiotherapy (RT) with or without adjunctive chemotherapy and nonsteroidal anti‐inflammatory drugs (NSAIDs).ObjectivesTo characterize event‐free and overall survival after treatment of CGUC using NSAIDs, mitoxantrone (MTX), and a standardized RT protocol (57 Gy in 20 fractions).AnimalsFifty‐one client‐owned dogs treated between 2008 and 2017.MethodsDogs were retrospectively categorized into treatment groups: (a) first‐line concurrent chemoradiotherapy (≥1 dose of MTX started within 1 month of RT); (b) first‐line chemotherapy (MTX administered for >1 month before RT without tumor progression); (c) RT as a salvage procedure (MTX, surgery or both with subsequent locoregional tumor progression before RT). Treatment‐induced toxicoses, event‐free survival (EFS), and overall survival times (OSTs) were recorded. The influence of demographics, staging, and treatment‐related factors on survival was assessed using Cox proportional hazards modeling.ResultsMedian EFS and OST for all dogs were 260 and 510 days with no significant differences among groups 1 (n = 39), 2 (n = 4), and 3 (n = 8). Both EFS and OST were shorter in dogs with moderate to severe clinical signs (P < .001 and P < .001, respectively); OST was shorter in dogs with prostatic involvement (P = .02). Permanent urinary incontinence developed in 16 dogs (31%) at a median of 70 days postirradiation; other toxicoses were mild and self‐limiting.Conclusions and Clinical ImportanceMild clinical signs and lack of prostate involvement were associated with favorable prognosis for survival. Client education regarding the risk of urinary incontinence is warranted.

No benefit after neoadjuvant chemoradiation in stage IV rectal cancer: A propensity score-matched analysis on a real-world population

BackgroundStage IV rectal cancer occurs in 25% of patients and locoregional control of primary tumor is usually poorly considered, since priority is the treatment of metastatic disease. AimsThis study evaluates impact of neoadjuvant chemoradiation followed by surgery (nCHRTS) vs. upfront surgery on locoregional control and overall survival in stage IV rectal cancer. MethodsAll patients diagnosed with stage IV rectal carcinoma between 2009 and 2019, undergone elective surgery at the National Cancer Institute of Milan (Italy), were included. Propensity score-based matching was performed between the two study groups. Loco-regional recurrence-free survival (LRRFS) and overall survival (OS) were analysed using Kaplan-Meyer method. ResultsA total of 139 patients were analyzed. After propensity score matching, 88 patients were included in the final analysis. The 3-yr LRRFS rates were 80.3% for nCHRTS vs. 90.4% for upfront surgery patients (p = 0.35). The 3-yr OS rates were respectively 81.8% vs. 58% (p = 0.36). KRAS mutation (HR 2.506, p = 0.038) and extra-liver metastases (HR 4.308, p = 0.003) were both predictive of worse OS in univariate analysis. ConclusionThe present study failed to demonstrate a significant impact of nCHRTS on LRRFS or OS in stage IV rectal cancer.

COMPARATIVE STUDY BETWEEN LAPAROSCOPIC VERSUS OPEN RIGHT HEMICOLECTOMY

Background: Colorectal cancer (CRC) incidence and mortality rates vary markedly around the world. The right colon has a thin wall, a large caliber, and its contents are liquid; thus, obstruction is a late event in right colon cancer. Also, right colonic tumors grow large enough to be palpable through the abdominal wall before other symptoms appear. Objective: To compare between laparoscopic and open complete mesocolic excision with central vascular ligation in right colon cancer as regards technical feasibility, advantages and disadvantages of both procedures. Patients and Methods: This study was conducted on 30 patients admitted to Al-Azhar University Hospitals, and diagnosed as operable right sided colon cancer. It was prospectively conducted during the period from October 2019 to June 2020, and all the procedures were done on elective basis. Informed consents were obtained from all patients included in the study which approved by the local ethics committee of Al-Azhar University Hospitals. Patients were 7 (46.7%) males and 8(53.3%) females. Their ages ranged from 51 to 71 years with a mean age of 58.33±5.88 in laparoscopic technique, and ranged from 50 to 70 years with a mean age of 59.93±5.20 in open technique. Results: There was no statistical significant difference between the studied groups regarding the mean age, gender distribution, DM, hypertension and the tumor location. There was a statistical significant difference between the studied groups regarding the incision length as the incision of the open technique was longer than the laparoscopic technique, regarding the operative time and intraoperative blood loss as the laparoscopic technique take more time than the open technique and the intraoperative blood loss during the laparoscopic technique was less than the open technique. Conclusion: Complete mesocolic exicion(CME), with central vascular ligation is the novel key factor in the multimodal management of right colon cancer, determining a significant improvement in loco-regional control of tumors and improving the long-term oncological outcome, especially in intermediate stages of disease. it is a safe, valid, and feasible surgical method for right colon cancers, associated with smaller incisions, less operative blood loss, earlier recovery after operation, and shorter hospital stay compared with Open technique. The open technique is still superior in shorter operative time and more number of harvested lymph nodes.

Cancer field surgery for locoregional tumor control of cervical carcinoma

Journal of Cancer Metastasis and Treatment is an open access journal, focusing on basic and clinical studies related to cancer cell, cell biology, oncology, radiation therapy and radiology, obstetrics and gynecology, pediatrics, surgery, hematology, neuro-oncology, etc.

Definition and validation of a radiomics signature for loco-regional tumour control in patients with locally advanced head and neck squamous cell carcinoma

PurposeTo develop and validate a CT-based radiomics signature for the prognosis of loco-regional tumour control (LRC) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC) treated by primary radiochemotherapy (RCTx) based on retrospective data from 6 partner sites of the German Cancer Consortium - Radiation Oncology Group (DKTK-ROG). Material and methodsPre-treatment CT images of 318 patients with locally advanced HNSCC were collected. Four-hundred forty-six features were extracted from each primary tumour volume and then filtered through stability analysis and clustering. First, a baseline signature was developed from demographic and tumour-associated clinical parameters. This signature was then supplemented by CT imaging features. A final signature was derived using repeated 3-fold cross-validation on the discovery cohort. Performance in external validation was assessed by the concordance index (C-Index). Furthermore, calibration and patient stratification in groups with low and high risk for loco-regional recurrence were analysed. ResultsFor the clinical baseline signature, only the primary tumour volume was selected. The final signature combined the tumour volume with two independent radiomics features. It achieved moderately good discriminatory performance (C-Index [95% confidence interval]: 0.66 [0.55–0.75]) on the validation cohort along with significant patient stratification (p = 0.005) and good calibration. ConclusionWe identified and validated a clinical-radiomics signature for LRC of locally advanced HNSCC using a multi-centric retrospective dataset. Prospective validation will be performed on the primary cohort of the HNprädBio trial of the DKTK-ROG once follow-up is completed.

Outcomes of Breast Brachytherapy in Stage I Breast Cancer – Data from a Large Health System

Accelerated partial breast irradiation (APBI) can be accomplished with a variety of techniques. Randomized trial data exist to support the efficacy of APBI utilizing external beam radiotherapy and interstitial multi-catheter-based brachytherapy, techniques that encompass a large volume of breast tissue. Far less data is available for smaller volume APBI techniques such as intraoperative radiotherapy (IORT) and single-entry brachytherapy devices. NSABP B-39 was the only randomized trial to include single-entry brachytherapy within the APBI arm, but too few patients received this technique to allow for a subset analysis. TARGIT-A is the only trial to evaluate photon IORT with short follow-up. Current study leverages the large patient volume of a university health system to review the experience of smaller volume APBI techniques. We hypothesize that smaller volume APBI would show inferior outcomes in loco-regional tumor control compared to larger volume APBI or whole breast irradiation in stage I breast cancer patients. The shared electronic health record of multiple institutions of a university health system was queried to identify women with either DCIS, T1N0 or T2N0 breast cancer treated with BCS between 2011 and 2014. The data collection included demographic features, known prognostic factors, tumor characteristics, treatment type, and evidence of local or regional recurrence (LRR). For the purposes of this study, the analysis was restricted to those patients treated with IORT or single-entry brachytherapy. The search identified 1386 patients who met criteria. Of these, 112 (8%) were treated with IORT to 20 Gy in a single fraction, and 116 (8%) underwent brachytherapy with a strut-adjusted volume implant (SAVI) device to 34 Gy in 10 fractions delivered twice daily. The demographic and tumor variables are listed below. The five-year rate of LRR among women treated with IORT was 3.4%, and 1.9% for women treated with SAVI brachytherapy using Kaplan-Meier estimate. In the evaluation of treatments for which randomized data are scarce, non-randomized series are vital. Health system consolidation facilitates the compilation of larger multi-hospital experiences. We report on a series of 228 low-risk patients treated with either IORT or SAVI brachytherapy with a single hospital system. The resulting LRR rates are relatively low, reflecting the trend of most modern series. Our next initiative will be to compare these outcomes to those seen for external beam radiotherapy within the same system.Abstract 2089; TableIORT (n = 112)SAVI (n = 116)Median Follow-up (mo.)67 (2.4-102)68 (1-92)Age (median)67 (49-90)59 (43-90)Stage DCIS127 T1mic1- T1a2015 T1b3330 T1c5443 T231Tumor Markers ER+111109 H2N+33 Triple -16 LVI +31 Open table in a new tab

Comprehensive Analysis of Tumour Sub-Volumes for Radiomic Risk Modelling in Locally Advanced HNSCC.

Simple SummaryRadiomic risk models are usually based on imaging features, which are extracted from the entire gross tumour volume (GTV). This approach does not explicitly consider the complex biological structure of the tumours. Therefore, in this retrospective study, we investigated the prognostic value of radiomic analyses based on different tumour sub-volumes using computed tomography imaging of patients with locally advanced head and neck squamous cell carcinoma who were treated with primary radio-chemotherapy. The GTV was cropped by different margins to define the rim and corresponding core sub-volumes of the tumour. Furthermore, the best performing tumour rim sub-volume was extended into surrounding tissue with different margins. As a result, the models based on the 5 mm tumour rim and on the 3 mm extended rim sub-volume showed an improved performance compared to models based on the corresponding tumour core. This indicates that the consideration of tumour sub-volumes may help to improve radiomic risk models.Imaging features for radiomic analyses are commonly calculated from the entire gross tumour volume (GTV). However, tumours are biologically complex and the consideration of different tumour regions in radiomic models may lead to an improved outcome prediction. Therefore, we investigated the prognostic value of radiomic analyses based on different tumour sub-volumes using computed tomography imaging of patients with locally advanced head and neck squamous cell carcinoma. The GTV was cropped by different margins to define the rim and the corresponding core sub-volumes of the tumour. Subsequently, the best performing tumour rim sub-volume was extended into surrounding tissue with different margins. Radiomic risk models were developed and validated using a retrospective cohort consisting of 291 patients in one of the six Partner Sites of the German Cancer Consortium Radiation Oncology Group treated between 2005 and 2013. The validation concordance index (C-index) averaged over all applied learning algorithms and feature selection methods using the GTV achieved a moderate prognostic performance for loco-regional tumour control (C-index: 0.61 ± 0.04 (mean ± std)). The models based on the 5 mm tumour rim and on the 3 mm extended rim sub-volume showed higher median performances (C-index: 0.65 ± 0.02 and 0.64 ± 0.05, respectively), while models based on the corresponding tumour core volumes performed less (C-index: 0.59 ± 0.01). The difference in C-index between the 5 mm tumour rim and the corresponding core volume showed a statistical trend (p = 0.10). After additional prospective validation, the consideration of tumour sub-volumes may be a promising way to improve prognostic radiomic risk models.

The prognostic value of the lymph node ratio for local advanced gastric cancer patients with intensity-modulated radiation therapy and concurrent chemotherapy after radical gastrectomy in China

BackgroundNearly 50% of new gastric cancer cases and gastric cancer-related deaths worldwide occur in China. No global consensus has been reached about the optimal management of locally advanced gastric cancer. Although the Guidelines for the Diagnosis and Treatment of Gastric Cancer from the National Health Commission of China, which has been updated three times since 2010, explicitly emphasize the necessity of adjuvant chemoradiation, few clinical institutions in China routinely adhere to the recommended radiotherapy guidelines. This study aimed to examine the efficacy, in terms of locoregional control and long-term survival, and the safety of adjuvant radiotherapy using intensity-modulated radiation therapy (IMRT) with concurrent and adjuvant fluoropyrimidine-based chemotherapy for gastric cancer.MethodsThis was a retrospective evaluation of 156 patients with high-risk gastric cancer who underwent adjuvant chemoradiotherapy between September 2008 and May 2019. The prescribed planning target volume median dose was 45 Gy in 1.8 Gy daily fractions, and all patients received concurrent and adjuvant fluoropyrimidine-based chemotherapy. Locoregional control, distant metastasis, and overall survival rates were estimated. Clinicopathological characteristics and patterns of failure were retrospectively reviewed to identify factors associated with survival and recurrence.ResultsThe median follow-up duration was 56 months (range 3–130 months) for all patients. Of the patients, 11 (7.1%) were lost to follow-up, and 49 (31.4%) and 104 (66.7%) had stage II or III disease according to the eighth edition of the American Joint Committee on Cancer tumor-node-metastasis staging criteria. The frequencies of acute grade 3 or 4 gastrointestinal and hematological toxicity were 9.6% and 10.9%, respectively. In total, 152 patients (97.4%) completed the entire chemoradiation regimen. No toxicity-related deaths occurred. Nineteen patients (12.2%) had locoregional recurrence, 26 (16.7%) had distant metastases, and 12 (7.7%) had peritoneal metastasis. The overall survival (OS) rates were 83.5%, 65.0%, and 59.5%, while the disease-free survival rates were 75.1%, 61.0%, and 55.6% at 1, 3, and 5 years, respectively. In the multivariate analysis, age, pathological T stage and lymph node ratio (LNR) were found to be independent predictors of OS.ConclusionPostoperative concomitant IMRT and chemotherapy were well tolerated, with acceptable toxicities and encouraging locoregional tumor control and long-term survival. The LNR can be used as an important prognostic indicator for OS. Adjuvant chemoradiotherapy should be considered for all patients with a high risk of locoregional recurrence, especially in China.

2D and 3D convolutional neural networks for outcome modelling of locally advanced head and neck squamous cell carcinoma

For treatment individualisation of patients with locally advanced head and neck squamous cell carcinoma (HNSCC) treated with primary radiochemotherapy, we explored the capabilities of different deep learning approaches for predicting loco-regional tumour control (LRC) from treatment-planning computed tomography images. Based on multicentre cohorts for exploration (206 patients) and independent validation (85 patients), multiple deep learning strategies including training of 3D- and 2D-convolutional neural networks (CNN) from scratch, transfer learning and extraction of deep autoencoder features were assessed and compared to a clinical model. Analyses were based on Cox proportional hazards regression and model performances were assessed by the concordance index (C-index) and the model’s ability to stratify patients based on predicted hazards of LRC. Among all models, an ensemble of 3D-CNNs achieved the best performance (C-index 0.31) with a significant association to LRC on the independent validation cohort. It performed better than the clinical model including the tumour volume (C-index 0.39). Significant differences in LRC were observed between patient groups at low or high risk of tumour recurrence as predicted by the model (p=0.001). This 3D-CNN ensemble will be further evaluated in a currently ongoing prospective validation study once follow-up is complete.

Postoperative radiotherapy with intensity-modulated radiation therapy versus 3-dimensional conformal radiotherapy in early breast cancer: A randomized clinical trial of KROG 15-03

PurposeTo investigate the safety and efficacy of intensity-modulated radiation therapy (IMRT) for early breast cancer compared with 3-dimensional conformal radiotherapy (3D-CRT) in a prospective and randomized trial. Methods and materialsFrom March 2015 to February 2018, 693 patients with pT1-2N0M0 early breast cancer who underwent breast-conserving surgery were enrolled and randomly assigned into IMRT and 3D-CRT. The primary endpoint was 3-year locoregional recurrence-free survival (LRRFS). The secondary endpoints were recurrence-free survival, overall survival, acute toxicity, target coverage index, irradiation dose to organs at risk, and fatigue inventory. The radiation dose for the 3D-CRT arm was 59.4 Gy in 33 fractions for 6.5 weeks. It was 57.4 Gy in 28 fractions with simultaneous integrated boost for 5.5 weeks for the IMRT arm. ResultsOf 693 patients, 349 and 344 patients received 3D-CRT and IMRT, respectively. There was no significant difference in LRRFS between the two arms. Conformity index of planning target volume was significantly superior in the IMRT arm than the 3D-CRT arm (p < 0.001). The mean lung dose and V5-V50 for the ipsilateral lung were significantly lower in the IMRT arm than the 3D-CRT arm (all p < 0.05). The incidence of grade 2 or higher dermatitis was significantly lower in the IMRT arm (p = 0.009). ConclusionCompared to 3D-CRT, IMRT showed similar results in locoregional tumor control but superior results in planning target volume coverage. When IMRT is used in breast cancer, the irradiation dose to an ipsilateral lung and skin toxicity can be reduced.

Radiation with concurrent radiosensitizing capecitabine tablets and single-dose mitomycin-C for muscle-invasive bladder cancer: A convenient alternative to 5-fluorouracil

Background and purposeChemoradiation (CRT) with mitomycin-C (MMC) and 5-fluorouracil (5-FU) has been shown to be superior to radiation alone in patients with muscle-invasive bladder cancer (MIBC). MMC/capecitabine is an effective replacement for 5FU as a radiosensitizer in other malignancies but has not been studied in bladder cancer. We evaluated the outcomes of MIBC patients treated with concurrent radiation and MMC/capecitabine. Materials and methodsMIBC patients treated with CRT (60 Gy in 5 weeks with single-dose MMC and capecitabine orally twice daily) between 2014 and 2019 were identified. Acute (<90 days) and late toxicity were registered. Endpoints were clinical complete response (cCR) in the bladder assessed by cystoscopy 3 months after CRT, locoregional disease-free survival (LDFS) and the number of salvage cystectomies. ResultsWe analysed 71 cT2-4aN0-2 M0 MIBC patients (median age 70 years). Twenty-one (30%) patients received neoadjuvant or induction chemotherapy and 14 (20%) patients underwent a pelvic lymph node dissection prior to CRT. All patients received the full dose of planned radiation. Seven (10%) patients experienced acute grade 3–4 toxicities and 2 (3%) patients experienced late grade 3–4 toxicities. Sixty-eight (96%) patients achieved cCR. Eight (11%) patients had a bladder recurrence, of whom 3 (4%) required salvage cystectomy. Two-year LDFS was 79% (95% CI: 68–88) at a median follow-up of 23 (95% CI: 17–28) months. ConclusionRadiation with concurrent MMC/capecitabine is a well-tolerated bladder-sparing treatment. Severe toxicity is infrequent and locoregional tumor control and short-term disease free survival appear similar to previous studies with MMC/5FU.

Nimotuzumab for Patients With Inoperable Cancer of the Head and Neck.

EGFR activation induces cell proliferation, neoformation of blood vessels, survival, and metastasis of the cancer cells. Nimotuzumab is an engineered, intermediate affinity anti-EGFR antibody, that apart from other drugs in its class, is very safe and does not cause hypomagnesemia or grade 3–4 cutaneous rash. The antibody inhibits cell proliferation and angiogenesis, activates natural killer cells, stimulates dendritic cell maturation, and induces cytotoxic T cells. Nimotuzumab restores MHC-I expression on tumor cells, hindering one of the EGFR immune-escape ways. The antibody has been extensively studied in 7 clinical trials, concurrently with irradiation or irradiation plus chemotherapy in subjects with inoperable head and neck tumors. Nimotuzumab was safe and efficacious in unfit patients receiving irradiation alone and in subjects treated with cisplatin and radiotherapy. In patients with locally advanced squamous cell carcinomas of the head and neck, nimotuzumab in combination with low dose cisplatin and radiotherapy was superior to cisplatin and radiotherapy in progression free survival, disease free survival, and locoregional tumor control.

Comparison of GeneChip, nCounter, and Real-Time PCR–Based Gene Expressions Predicting Locoregional Tumor Control after Primary and Postoperative Radiochemotherapy in Head and Neck Squamous Cell Carcinoma

This article compares the expression and applicability of biomarkers, from single genes and gene signatures, identified in patients with locally advanced head and neck squamous cell carcinoma using the GeneChip Human Transcriptome Array 2.0, nCounter, and real-time PCR analyses. Two multicenter, retrospective cohorts of patients with head and neck squamous cell carcinoma from the German Cancer Consortium Radiation Oncology Group who received postoperative radiochemotherapy or primary radiochemotherapy were considered. Real-time PCR was performed for a limited number of 38 genes of the cohort who received postoperative radiochemotherapy only. Correlations between the methods were evaluated by the Spearman rank correlation coefficient. Patients were stratified based on the expression of putative cancer stem cell markers, hypoxia-associated gene signatures, and a previously developed seven-gene signature. Locoregional tumor control was compared between these patient subgroups using log-rank tests. Gene expressions obtained from nCounter analyses were moderately correlated to GeneChip analyses (median ρ = approximately 0.68). A higher correlation was obtained between nCounter analyses and real-time PCR (median ρ=0.84). Significant associations with locoregional tumor control were observed for most of the considered biomarkers evaluated by GeneChip and nCounter analyses. In general, all applied biomarkers (single genes and gene signatures) classified approximately 70% to 85% of the patients similarly. Overall, gene signatures seem to be more robust and had a better transferability among different measurement methods.

Definitive chemoradiotherapy in patients with squamous cell cancers of the head and neck - results from an unselected cohort of the clinical cooperation group \u201cPersonalized Radiotherapy in Head and Neck Cancer\u201d

BackgroundDefinitive chemoradiotherapy (dCRT) is a standard treatment for patients with locally advanced head and neck cancer. There is a clinical need for a stratification of this prognostically heterogeneous group of tumors in order to optimize treatment of individual patients. We retrospectively reviewed all patients with head and neck squamous cell carcinoma (HNSCC) of the oral cavity, oropharynx, hypopharynx, or larynx, treated with dCRT from 09/2008 until 03/2016 at the Department of Radiation Oncology, LMU Munich. Here we report the clinical results of the cohort which represent the basis for biomarker discovery and molecular genetic research within the framework of a clinical cooperation group.MethodsPatient data were collected and analyzed for outcome and treatment failures with regard to previously described and established risk factors.ResultsWe identified 184 patients with a median follow-up of 65 months and a median age of 64 years. Patients received dCRT with a median dose of 70 Gy and simultaneous chemotherapy in 90.2% of cases, mostly mitomycin C / 5-FU in concordance with the ARO 95–06 trial. The actuarial 3-year overall survival (OS), local, locoregional and distant failure rates were 42.7, 29.8, 34.0 and 23.4%, respectively. Human papillomavirus-associated oropharynx cancer (HPVOPC) and smaller gross tumor volume were associated with significantly improved locoregional tumor control rate, disease-free survival (DFS) and OS in multivariate analysis. Additionally, lower hemoglobin levels were significantly associated with impaired DFS und OS in univariate analysis. The extent of lymph node involvement was associated with distant failure, DFS and OS. Moreover, 92 patients (50%) of our cohort have been treated in concordance with the ARO 95–06 study, corroborating the results of this study.ConclusionOur cohort is a large unselected monocentric cohort of HNSCC patients treated with dCRT. Tumor control rates and survival rates compare favorably with the results of previously published reports. The clinical data, together with the available tumor samples from biopsies, will allow translational research based on molecular genetic analyses.