Stereotactic Radiotherapy in Combination with Immunotherapy in Treatment of Advanced Recurrent Squamous Cell Carcinoma of the Larynx.

Squamous cell carcinoma (SCC) of the larynx in advanced stages is a challenging malignancy to treat with a high recurrence and death rate. An individualized approach to treatment is crucial in such patients. We present a 58-year-old male patient with SCC of the larynx in the T3N0M0 stage who was treated with concurrent radiochemotherapy. A total of 17 months after the radical treatment, the patient underwent a laryngectomy due to recurrence. A total of 11 months after the operation, local failure was diagnosed. In the next order, the patient received six cycles of palliative chemotherapy according to cisplatin 100 mg/m2 and 5-fluorouracil 1000 mg/m2. After three months, due to progression, Nivolumab-based immunotherapy was administered, ensuring disease stabilization. After the 56th cycle of Nivolumab, another progression was documented. The addition of stereotactic radiotherapy (18 Gy in three fractions) to immunotherapy led to significant regression of the disease and enabled the continuation of Nivolumab to the 70th cycle. The presented case demonstrates the usefulness of the combination of stereotactic radiotherapy with immunotherapy in prolonging the local control.

Stereotactic Radiotherapy Boost in Treatment of Persistent Periocular Sebaceous Carcinoma after Surgery.

Sebaceous carcinoma is a rare malignancy that should be treated with surgical resection. Nonetheless, a dynamic and aggressive course of the disease may disqualify a patient from this treatment. Applying radiotherapy with the escalation dose using a stereotactic boost is worthy of consideration as a radical treatment. In this paper, we present the case study of a young patient with a tumor localized in the periocular area. The patient was treated with operation two times without a satisfactory effect. Conventional radiotherapy, 60 Gy in 30 fractions, combined with chemotherapy based on cisplatin 40 mg/m2 and the addition of a stereotactic radiosurgery boost were administered. The tolerance of this treatment was acceptable. During the 2-year follow-up, local and distant recurrences were not diagnosed. The presented case shows the usefulness of an individualized approach in the radical treatment of sebaceous carcinoma with the use of the stereotactic radiotherapy boost. This is a subsequent example of the implementation of the boost in head and neck carcinoma, which yields a positive result.

Escalating a Biological Dose of Radiation in the Target Volume Applying Stereotactic Radiosurgery in Patients with Head and Neck Region Tumours.

Background: The treatment of head and neck tumours is a complicated process usually involving surgery, radiation therapy, and systemic treatment. Despite the multidisciplinary approach, treatment outcomes are still unsatisfactory, especially considering malignant tumours such as squamous cell carcinoma or sarcoma, where the frequency of recurrence has reached 50% of cases. The implementation of modern and precise methods of radiotherapy, such as a radiosurgery boost, may allow for the escalation of the biologically effective dose in the gross tumour volume and improve the results of treatment. Methods: The administration of a stereotactic radiotherapy boost can be done in two ways: an upfront boost followed by conventional radio(chemo)therapy or a direct boost after conventional radio(chemo)therapy. The boost dose depends on the primary or nodal tumour volume and localization regarding the organs at risk. It falls within the range of 10-18 Gy. Discussion: The collection of detailed data on the response of the disease to the radiosurgery boost combined with conventional radiotherapy as well as an assessment of early and late toxicities will contribute crucial information to the prospective modification of fractionated radiotherapy. In the case of beneficial findings, the stereotactic radiosurgery boost in the course of radio(chemo)therapy in patients with head and neck tumours will be able to replace traditional techniques of radiation, and radical schemes of treatment will be possible for future development.

High-dose stereotactic radiotherapy boost in the treatment of squamous cell carcinoma of the head and neck region.

BACKGROUND: Surgical resection with adjuvant concurrent radiochemotherapy is the standard of care for stage III-IV oral cavity cancer. In some cases, the dynamic course of the disease is out of the prepared schedule of treatment. In that event, a stereotactic radiosurgery boost might be the only chance for disease control. CASE PRESENTATION: Here, we present a case study of a patient with oral cancer who underwent surgery. During adjuvant radiotherapy, a metastatic cervical lymph node was diagnosed based on fine-needle aspiration biopsy. To increase the total dose to the metastatic tumor, a stereotactic radiosurgery boost of 1 × 18 Gy was performed two days after the last fraction of conventional radiotherapy. The early and late tolerance of this treatment were positive. During the 18-month follow-up, locoregional recurrence was not detected. The patient died due to secondary malignancy. CONCLUSIONS: This paper shows that a stereotactic radiosurgery boost added to adjuvant conventional radiotherapy is an effective approach permitting the maintenance of good local control in well-selected patients.

Dose-dependence of radiotherapy-induced changes in serum levels of choline-containing phospholipids; the importance of lower doses delivered to large volumes of normal tissues.

BACKGROUND: Conformal radiotherapy is a primary treatment in head and neck cancer, which putative adverse effects depend on relatively low doses of radiation delivered to increased volumes of normal tissues. Systemic effects of such treatment include radiation-induced changes in serum lipid profile, yet dose- and volume-dependence of these changes remain to be established. METHODS: Here we analyzed levels of choline-containing phospholipids in serum samples collected consecutively during the radiotherapy used as the only treatment modality. The liquid chromatography-mass spectrometry (LC-MS) approach applied in the study enabled the detection and quantitation of 151 phospholipids, including (lyso)phosphatidylcholines and sphingomyelins. RESULTS: No statistically significant differences were found in the pretreatment samples from patients with different locations and stages of cancer. To compensate for potential differences between schemes of radiotherapy, the biologically effective doses were calculated and used in the search of correlations with specific lipid levels. We found that the levels of several phospholipids depended on the maximum dose delivered to the gross tumor volume and total radiation energy absorbed by the patient's body. Increased doses correlated with increased levels of sphingomyelins and reduced levels of phosphatidylcholines. Furthermore, we observed several phospholipids whose serum levels correlated with the degree of acute radiation toxicity. CONCLUSION: Noteworthy, serum phospholipid levels were associated mainly with volumes of normal tissues irradiated with relatively low doses (i.e., total accumulated dose 20 Gy), which indicated the importance of such effects on the systemic response of the patient's organism to intensity-modulated radiotherapy (IMRT).

Successful Treatment of Adenoid Cystic Carcinoma with the Application of a High-Dose Stereotactic Body Radiotherapy Boost.

BACKGROUND: Adenoid cystic carcinoma (ACC) should be treated with a surgical procedure. Unfortunately, in some cases, such procedures are impossible to perform. In that event, radiotherapy can be used as a form of radical treatment, although ACC is established as a radio- and chemoresistant tumour. Therefore, unconventional fractionated radiotherapy needs to be considered. CASE PRESENTATION: Here, we present a case study of a patient with an unresectable tumour of the choanae and nasopharynx treated with a stereotactic radiotherapy boost in combination with conventional radiotherapy. We achieved complete clinical regression after application of a 1 × 18 Gy boost followed by conventional radiotherapy at 50 Gy in 25 fractions. The early and late tolerance of this treatment were positive. During the 2-year follow-up, local and distant recurrence were not detected. CONCLUSIONS: This case represents an individualized, modern and safe approach to unresectable ACC. This is one of the first cases to show the use of a combination of stereotactic and conventional radiotherapy in radical, conservative cancer treatment.

The analysis of absorbed dose by pancreas during gastric cancer radiotherapy.

INTRODUCTION: The toxicity of radiotherapy is a very important issue in the everyday work of radiation oncologist. The tolerance to certain doses of radiotherapy in organs at risk determines the safety of radiotherapy. Despite the increasing number of publications concerning the injury of the pancreas after radiotherapy, this organ does not have common directives. We decided to reanalyse our previously published data in terms of the dose of radiation absorbed by the pancreas to determine a dose-effect relationship with the use of radiation-induced hypoamylasaemia and hypolipasaemia. MATERIALS AND METHODS: We reanalysed a group of 127 gastric cancer patients after preoperative or postoperative chemoradiotherapy who were treated with a total dose of 45 Gy administered in 25 fractions. To identify the absorbed doses, the pancreas was contoured based on the CT scans used for radiotherapy planning and divided into anatomical parts: the head, the body and the tail. RESULTS: We found that 80% of the whole pancreatic volume absorbed at least 44.5 Gy. The body, tail and head absorbed 100%, 90% and 70% of the abovementioned dose, respectively. The mean dose absorbed by the whole pancreas ranged from 32 to 48 Gy, with a mean of 44 Gy. A total dose of 45 Gy administered to gastric cancer patients can lead to subclinical insufficiency of the pancreas (hypolipasaemia and hypoamylasaemia). This dose is not able to cause symptomatic damage to the pancreas.

Can we obtain planning goals for conformal techniques in neoadjuvant and adjuvant radiochemotherapy for gastric cancer patients?

AIM: The purpose of this study was to compare conformal radiotherapy techniques used in the treatment of gastric cancer patients. The study is dedicated to radiotherapy centres that have not introduced dynamic techniques in clinical practice. BACKGROUND: The implementation of multi-field technique can minimise the toxicity of treatment and improve dose distribution homogeneity in the target volume with simultaneous protection of organs at risk (OaRs). Treatment plan should be personalised for each patient by taking into account the planning target volume and anatomical conditions of the individual patient. MATERIALS AND METHODS: For each patient, four different three dimensional conformal plans were compared: 2-field plan, 3-field plan, non-coplanar 3-field plan and non-coplanar 4-field plan. Dose distributions in a volume of 107% of the reference dose, and OaRs such as the liver, kidneys, intestines, spinal cord, and heart were analysed. RESULTS: The mean volume of the patient body covered using the isodose of 107% was 3004.73 cm(3), 1454.28 cm(3), 1426.62 cm(3), 889.14 cm(3) for the 2-field, 3-field, non-coplanar 3-field and non-coplanar 4-field techniques, respectively. For all plans the minimum dose in the PTV volume was at least 95% of the reference dose. The QUANTEC protocol was used to investigate doses in OaRs. CONCLUSIONS: Comparison of 3D conformal radiotherapy techniques in gastric cancer patients indicates that none of the plans can fulfil simultaneously all of the criteria of the tolerance dose in the organs at risk. The implementation of the multi-field technique can minimise the toxicity of treatment and improve dose distribution homogeneity in the target volume with additional protection of organs at risk (OaRs).

Radiation-induced injury of the exocrine pancreas after chemoradiotherapy for gastric cancer.

BACKGROUND AND PURPOSE: The pancreas is located almost entirely within the treatment area for radiotherapy of gastric cancer. The aim of this study was to analyze radiation-induced injury of the exocrine pancreas. MATERIAL AND METHODS: The study included 127 gastric cancer patients, who underwent preoperative or postoperative chemoradiotherapy. A total dose of 45 Gy was given in 25 fractions. Concurrent chemotherapy was 5-fluorouracil-based. Lipase and α-amylase were assayed before, during and after treatment. RESULTS: Lipase and α-amylase deficiencies were found in 48.2% and 19.7% of patients, respectively. In the univariant analysis, age and pretreatment α-amylase and lipase activities influenced on risk of injury of the exocrine pancreas (p<0.05). Younger patients (<65 years) had a lower risk of hypoamylasemia than older patients. The probability of insufficiency was lower than 0.2 for patients with pretreatment α-amylase and lipase activities above 50 U/L and 55 U/L, respectively. The multivariate analyses of the time to hypolipasemia showed that only pretreatment lipase activity was significant. CONCLUSIONS: Gastric cancer patients have an increased risk of exocrine pancreatic insufficiency after chemoradiotherapy. Thus, the pancreas should be regarded as an OAR. Measuring lipase activity should be the standard for assessing radiation-induced pancreatic injury.

Identification of serum proteome signatures of locally advanced and metastatic gastric cancer: a pilot study.

BACKGROUND: The gastric cancer is one of the most common and mortal cancer worldwide. The initial asymptomatic development and further nonspecific symptoms result in diagnosis at the advanced stage with poor prognosis. Yet, no clinically useful biomarkers are available for this malignancy, and invasive gastrointestinal endoscopy remains the only reliable option at the moment. Hence, there is a need for discovery of clinically useful noninvasive diagnostic and/or prognostic tool as an alternative (or complement) for current diagnostic tools. Here we aimed to search for serum proteins characteristic for local and invasive gastric cancer. METHODS: Pre-treatment blood samples were collected from patients with diagnosed gastric adenocarcinoma at the different stage of disease: 35 patients with locally advanced cancer and 18 patients with metastatic cancer; 50 healthy donors were also included as a control group. The low-molecular-weight fraction of serum proteome (i.e., endogenous peptidome) was profiled by the MALDI-ToF mass spectrometry, and the whole proteome components were identified and quantified by the LC-MS/MS shotgun approach. RESULTS: Multicomponent peptidome signatures were revealed that allowed good discrimination between healthy controls and cancer patients, as well as between patients with locally advanced and metastatic cancer. Moreover, a LC-MS/MS approach revealed 49 serum proteins with different abundances between healthy donors and cancer patients (predominantly proteins associated with inflammation and acute phase response). Furthermore, 19 serum proteins with different abundances between patients with locally advanced and metastatic cancer were identified (including proteins associated with cytokine/chemokine response and metabolism of nucleic acids). However, neither peptidome profiling nor shotgun proteomics approach allowed detecting serum components discriminating between two subgroups of patients with local disease who either developed or did not develop metastases during follow-up. CONCLUSIONS: The molecular differences between locally advanced and metastatic gastric cancer, as well as more obvious differences between healthy individuals and cancer patients, have marked reflection at the level of serum proteome. However, we have no evidence that features of pre-treatment serum proteome could predict a risk of cancer dissemination in patients treated due to local disease. Nevertheless, presented data confirmed potential applicability of a serum proteome signature-based biomarker in diagnostics of gastric cancer.

Radiotherapy and chemoradiotherapy as a novel option for the treatment of locally advanced inoperable gastric adenocarcinoma: A phase II study.

This phase II trial aimed to evaluate the tolerance and efficacy of radical radiotherapy or chemoradiotherapy in patients with primarily inoperable gastric cancer. The analysis was based on 13 patients with primarily inoperable gastric cancer. A total of 6 (46.2%) patients refused surgery and 7 (53.8%) had contraindications to anesthesia due to cardiological or respiratory reasons (4 and 3 patients, respectively). The treatment regimen consisted of radiotherapy and chemotherapy based on 5-fluorouracil. Half of the patients were not qualified to receive chemotherapy due to the presence of comorbidities. A total dose of 45 Gy was administered in 25 fractions. Of the 13 patients who started treatment, 12 (92.3%) completed radiotherapy. Local treatment response was observed in 6/12 patients (50%), with 5/12 (41.7%) displaying clinical complete response and 1/12 (8.3%) partial response. The 1- and 3-year overall survival rates and the median survival were 59 and 48% and 17.1 months, respectively. In conclusion, radical radiotherapy, either alone or in combination with chemotherapy, is safe for patients with inoperable locally advanced gastric cancer and may prolong survival.