Combined Modality Approach Research Articles

Toward precision medicine in inflammatory breast cancer.

Inflammatory breast cancer (IBC) is an aggressive, although infrequent form of invasive breast cancer. Despite some advances in systemic treatment, even in the early setting, with combined-modality approach being the current recommended standard of care, the prognosis of IBC still remains unfavorable and has not significantly improved over time. Thus, a better understanding of the biology of IBC is eagerly awaited in order to identify possible targets for new drug development. This paper aims to provide an overview on recent data on the molecular and biological features of IBC and on possible targetable pathways. Molecular subtypes of IBC, similarly to other forms of breast cancer, have both therapeutic and prognostic implications. Moreover, few activated pathways have been described in IBC, including angiogenesis, epidermal growth factor receptor (EGFR), Janus kinase/signal transducer of activation (JAK/STAT) signaling and phosphoinositide 3-kinase/Akt/mTOR (PI3K/AKT/mTOR) pathways. However, when tested in clinical trials, agents targeting these pathways have provided only small benefit. Several clinical trials are currently ongoing investigating combination of standard chemotherapeutics, new targeted agents and immunotherapy. Moreover, tumor microenvironment (TME) is likely to play a central role in the disease; targeting the components of the tumor stroma may represent an interesting therapeutic strategy.

Toward precision medicine in inflammatory breast cancer

Inflammatory breast cancer (IBC) is an aggressive, although infrequent form of invasive breast cancer. Despite some advances in systemic treatment, even in the early setting, with combined-modality approach being the current recommended standard of care, the prognosis of IBC still remains unfavorable and has not significantly improved over time. Thus, a better understanding of the biology of IBC is eagerly awaited in order to identify possible targets for new drug development. This paper aims to provide an overview on recent data on the molecular and biological features of IBC and on possible targetable pathways. Molecular subtypes of IBC, similarly to other forms of breast cancer, have both therapeutic and prognostic implications. Moreover, few activated pathways have been described in IBC, including angiogenesis, epidermal growth factor receptor (EGFR), Janus kinase/signal transducer of activation (JAK/STAT) signaling and phosphoinositide 3-kinase/Akt/mTOR (PI3K/AKT/mTOR) pathways. However, when tested in clinical trials, agents targeting these pathways have provided only small benefit. Several clinical trials are currently ongoing investigating combination of standard chemotherapeutics, new targeted agents and immunotherapy. Moreover, tumor microenvironment (TME) is likely to play a central role in the disease; targeting the components of the tumor stroma may represent an interesting therapeutic strategy.

Cabozantinib in Renal Cell Carcinoma With Brain Metastases: Safety and Efficacy in a Real-World Population

Cabozantinib showed efficacy and manageable toxicity in patients with metastatic renal cell carcinoma (mRCC). In this study we aimed to describe the safety and to collect evidence on the potential efficacy of cabozantinib in mRCC patients with brain metastases (BM) in a real-world experience. We retrospectively collected data of patients treated with cabozantinib within the Italian Managed Access Program. Patients were selected for the presence of BM before the start of treatment and for at least 1 previous tyrosine kinase inhibitor (TKI) treatment regimen for metastatic disease. Safety data were reported, and overall response rate (ORR), brain-specific response, progression-free survival (PFS), and median overall survival (OS) were analyzed. Overall, 12 patients treated with cabozantinib were evaluated. Any grade adverse events (AEs) accounted for 92%, Grade 3/4 AEs rated at 36% with no major neurological side effects. The most common AEs included hypertension (33%), fatigue (24%), aminotransferase elevation (25%), hypothyroidism (16%), and gastrointestinal toxicity (16%). The ORR was 50% with a disease control rate of 75%. All 5 patients treated with a combined systemic and brain-directed approach obtained intracranial disease control, without increased toxicity. Median PFS and median OS were 5.8 and 8.8 months, respectively. Comparable safety and tolerability results for other TKI regimens were reported from the literature. Cabozantinib showed safety, acceptable tolerability, and promising antitumor activity in a population of mRCC patients with BM from a real-world experience. A combined modality approach for renal cell carcinoma with BM, whenever feasible, could be recommended to improve oncological outcomes.

Management of Malignant Pleural Mesothelioma in the Elderly Population.

The median age at diagnosis for malignant pleural mesothelioma (MPM) is approximately 72years. Elderly patients pose unique management challenges because of the increased risk of therapy-related toxicities and mortality. Because there are no high-volume retrospective studies, prospective trials, or dedicated treatment recommendations for this population, this investigation addresses a major knowledge gap by examining national practice patterns and postoperative/survival outcomes in elderly MPM patients. The National Cancer Database was queried for patients aged ≥ 80years with newly diagnosed nonmetastatic MPM. Multivariable logistic regression ascertained factors associated with observation and surgery. Kaplan-Meier analysis assessed overall survival (OS), and multivariable Cox proportional hazards modeling examined factors associated with OS. Survival was also calculated following propensity matching. Additionally, postoperative outcomes were evaluated in surgical patients. Of 4526 patients, 2% received surgery and chemotherapy, 22% underwent chemotherapy alone, and 63% were observed. Respective median OS was 12.2, 9.5, and 4.1 months (p<0.001). Differences between all groups persisted following propensity matching (all comparisons p<0.05). For the 8% of patients who underwent specified definitive surgery (95% of whom received pleurectomy/decortication), 30- and 90-day mortality rates were 11.0% and 28.5%, respectively. The median length of postoperative hospitalization was 6days, with 30-day readmission occurring in 7.5% of patients. The majority of elderly MPM patients in the US are observed, which was associated with poorer OS than chemotherapy and/or surgery. Although highly selected surgery/chemotherapy patients were associated with the longest OS, given the high biases in database studies and high perioperative mortality rates, careful patient selection for combined modality approaches in this population is imperative.

Combining Radiation and Immune Checkpoint Blockade in the Treatment of Head and Neck Squamous Cell Carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is a significant cause of morbidity and mortality worldwide. Current treatment options, even though potentially curative, have many limitations including a high rate of complications. Over the past few years immune checkpoint inhibitors (ICI) targeting cytotoxic lymphocyte antigen-4 (CTLA-4), programmed cell death protein 1 (PD-1), and programmed cell death ligand 1 (PD-L1) have changed treatment paradigms in many malignancies and are currently under investigation in HNSCC as well. Despite improvements in treatment outcomes and the implementation of combined modality approaches long-term survival rates in patients with locally advanced HNSCC remain suboptimal. Accumulating evidence suggests that under certain conditions, radiation may be delivered in conjunction with ICI to augment efficacy. In this review, we will discuss the immune modulating mechanisms of ICI and radiation, how changing the dose, fractionation, and field of radiation may alter the tumor microenvironment (TME), and how these two treatment modalities may work in concert to generate durable treatment responses against HNSCC.

The management of primary mediastinal B-cell lymphoma: a British Society for Haematology Good Practice Paper.

This Good Practice Paper was compiled according to the British Society for Haematology (BSH) process at http://www.b-s-h.org.uk/guidelines. The BSH produces Good Practice Papers to recommend good practice in areas where there is a limited evidence base but for which a degree of consensus or uniformity is likely to be beneficial to patient care. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) nomenclature was used to evaluate levels of evidence and to assess the strength of recommendations. The GRADE criteria can be found at http://www.gradeworkinggroup.org and is also detailed in Table 1.

Coexistence of Multiple Metastatic Lesions Showing Various Grades of Differentiation in a Single Patient with Neuroendocrine Tumor of Lung as Primary: A Combined Modality Approach of 68Ga-DOTANOC Positron Emission Tomography/Computed Tomography and 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Imaging.

Neuroendocrine tumors (NETs) of gastrointestinal (GI) tract and lungs are a rare variety of tumors but given their indolent nature are quite prevalent. These tumors are mostly malignant in nature and are often diagnosed in advanced stages. GI tracts are the most common sites of NETs followed by lungs, thymus, and other less common sites being ovaries, testis, and hepatobiliary system. Nuclear medicine imaging modalities include 68Ga-DOTANOC positron emission tomography/computed tomography (PET/CT) which is sensitive for low-grade NETs and 18F-fluorodeoxyglucose (FDG) PET/CT which is more valuable for high-grade NETs. However, intermediate-grade NETs are equally sensitive to both 68Ga-DOTANOC PET/CT and 18F-FDG PET/CT.

Temozolamide-Associated Pancytopenia in a Patient with Glioblastoma Multiforme

Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor. GBM treatment is a combined modality approach involving maximum surgical resection, adjuvant postoperative radiation and adjuvant chemotherapy treatment.There is a greater risk of hematological toxicity in concurrent temozolomide and radiation therapy. We reported that pancytopenia has been developed on a 54-year old female patient with GBM after concurrently used temozolomide and radiotherapy treatment. It should be kept in mind that this side effect may develop because the risk of morbidity and mortality may be elevated. Therefore, supportive therapies should be started immediately in patients where this toxicity developed.

The Use of Adjuvant or Neoadjuvant Chemotherapy in Extremity and Truncal Sarcoma

Although neoadjuvant chemotherapy has been an established component of multimodality cancer care for patients with pediatric sarcomas for the past 25 years, the role of adjuvant or neoadjuvant chemotherapy in the management of adult patients with soft tissue sarcoma (STS) amenable to treatment with curative intent remains controversial. Overall, meta-analyses have revealed modest improvements in survival outcomes with the use of adjuvant or neoadjuvant chemotherapy, but individual trials have demonstrated inconsistent results leading some to question the robustness and external validity of the results. A recent randomized trial using anthracycline- and ifosfamide-based chemotherapy has provided further positive evidence in support of neoadjuvant chemotherapy for adult STS patients, but concerns persist regarding the risks of chemotherapy-related toxicities and the generalizability of the findings. Given the substantial risk of distant recurrence and disease-specific death for adult STS patients with tumors greater than 10 cm, especially those with synovial sarcoma and myxoid or round liposarcoma histologies, these patients should be strongly considered for neoadjuvant chemotherapy as part of a combined modality approach. The impact of recent level I data on the broader implementation of adjuvant or neoadjuvant chemotherapy in adult STS remains to be seen. This review contains 5 figures and 34 references Key Words: chemotherapy, limb salvage, myxoid/round cell liposarcoma, multimodality therapy, soft tissue sarcoma, surgery, survival, synovial sarcoma, undifferentiated pleomorphic sarcoma

The Use of Adjuvant or Neoadjuvant Chemotherapy in Extremity and Truncal Sarcoma

Although neoadjuvant chemotherapy has been an established component of multimodality cancer care for patients with pediatric sarcomas for the past 25 years, the role of adjuvant or neoadjuvant chemotherapy in the management of adult patients with soft tissue sarcoma (STS) amenable to treatment with curative intent remains controversial. Overall, meta-analyses have revealed modest improvements in survival outcomes with the use of adjuvant or neoadjuvant chemotherapy, but individual trials have demonstrated inconsistent results leading some to question the robustness and external validity of the results. A recent randomized trial using anthracycline- and ifosfamide-based chemotherapy has provided further positive evidence in support of neoadjuvant chemotherapy for adult STS patients, but concerns persist regarding the risks of chemotherapy-related toxicities and the generalizability of the findings. Given the substantial risk of distant recurrence and disease-specific death for adult STS patients with tumors greater than 10 cm, especially those with synovial sarcoma and myxoid or round liposarcoma histologies, these patients should be strongly considered for neoadjuvant chemotherapy as part of a combined modality approach. The impact of recent level I data on the broader implementation of adjuvant or neoadjuvant chemotherapy in adult STS remains to be seen. This review contains 5 figures and 34 references Key Words: chemotherapy, limb salvage, myxoid/round cell liposarcoma, multimodality therapy, soft tissue sarcoma, surgery, survival, synovial sarcoma, undifferentiated pleomorphic sarcoma

Toxicity Reduction in the Treatment of HPV Positive Oropharyngeal Cancer: Emerging Combined Modality Approaches.

Human papillomavirus positive (HPV+) oropharyngeal squamous cell carcinoma (OPC) is a distinct clinical entity within the head and neck cancers, with a unique epidemiology and, in general, a favorable prognosis. Because of this favorable prognosis, researchers have considered de-intensifying the current standard treatment of HPV+ OPC in order to reduce acute and late treatment related toxicity without compromising outcome. Current ongoing trials can be divided in three main categories: de-intensification of the chemotherapy by replacing concomitant platinum-based chemotherapy with the EGFR-inhibitor cetuximab, or de-intensification of the radiation dose of either the primary radiotherapy of selected, good-responding patients after induction chemotherapy or of the adjuvant radiotherapy based on pathology features after primary surgery. Despite the good prognosis of the majority of HPV+ OPC patients, a proportion of them still have poor prognosis. This unmet need has led clinical research on new treatment strategies focused on influencing the unique micro-environment of HPV+ OPC with for example immunotherapy. This article summarizes the current understanding regarding the optimal treatment of non-metastatic HPV+ OPC. Ongoing and published clinical trials regarding de-intensification strategies, immunotherapy and proton therapy are described focusing on the rationale and underlying evidence of these emerging treatment strategies. Nevertheless, until the results of the ongoing trials are known, the treatment of HPV+ OPC in clinical practice should remain identical to the treatment of HPV negative OPC.

Primary Gastrointestinal De Novo CD5+ CD23+ Diffuse Large B-Cell Lymphoma (DLBCL): A Different Treatment Approach

Primary gastrointestinal lymphoma is a very rare entity, constituting only about 1%- 4% of all gastrointestinal malignancies. Diffuse large B cell lymphoma (DLBCL) represents the most common histological subtype of primary gastrointestinal lymphoma. Aggressive CD5+ CD23+ primary gastrointestinal DLBCL is a very rare lymphoma representing a unique immunophenotypic and molecular subtype of DLBCL.2547_A Figure 1. CT scan showing primary ileocecal lymphomaThis is a 50-year-old gentleman who presented with symptomatic anemia secondary to severe iron deficiency. On imaging, he was found to have an exophytic soft tissue mass in the cecal tip adjacent to the appendix. His colonoscopy was consistent with a near circumferential large polypoid mass at the ileocecal valve extending into the terminal ileum. Biopsy of the ileocecal mass showed diffuse infiltrate of large (centroblast -like) lymphoid cells positive for CD20, CD5, CD23, CD43, BCL-2, BCL-6, c-MYC, MUM-1 and with Ki-67 of 60%. Fluorescent In Situ Hybridization (FISH) did not show any evidence for MYC, CCND1-IGH, BCL2-IGH, BCL-6 rearrangements. An abnormal hybridization pattern was detected in 50% of cells consistent with loss of 3' region of the MYC gene, which confers poor prognosis. The immunohistochemical and flow cytometry analysis resembled Richter syndrome although chronic lymphocytic leukemia was not pre-existing. His bone marrow biopsy was negative for any involvement of lymphoma and he did not have any evidence of lymphadenopathy or splenomegaly on imaging. His diagnosis was consistent with primary gastrointestinal de novo CD5+ CD23+ diffuse large B-cell lymphoma of activated B cell type with low to intermediate IPI (International Prognostic Index) score. Denovo CD5+ DLBCL lymphoma is a rare variant of lymphoma with a poor prognostic feature. Diagnosis and treatment is always a challenge in these subtypes due to a critical gap in the understanding of optimal management approaches due to the rarity of these tumors. Early tumor stage, right-sided lesion, the diffuse large B-cell histological pattern seems to be the clinical characteristics of optimal surgical candidates. Surgical resection followed by chemotherapy might be an effective treatment strategy with the acceptable quality of life (QOL) for localized intestinal DLBCL. Combined modality approach reduces the risk of treatment-related perfusion and also minimizes the exposure to toxic effects of chemotherapy by decreasing the duration of chemotherapy.2547_B Figure 2. Biopsy of ileocecal mass demonstrating large centroblast like lymphoid cells with positive B cell markers2547_C Figure 3. Laparoscopic resection of the ileocecal diffuse large B-cell lymphoma

Alternative Chemotherapy Schedules in Ewing's Sarcoma: An Indian Perspective

AbstractAdvances in the treatment of Ewing's sarcoma family of tumors (ESFTs) are a result of improvements in systemic and local therapies. VACA (vincristine, Adriamycin [doxorubicin], cyclophosphamide, dactinomycin) chemotherapy alone versus VACA + IE (VACA with alternate ifosfamide, etoposide) improve survival, but this regimen cannot be given to all patients due to poor tolerance and 5-day schedule chemotherapy in VACA + IE schedule. We reviewed the records of 50 patients treated as per our institutional protocols from 2007 to 2011. Two schedules of chemotherapy followed were vincristine, Adriamycin, cyclophosphamide (VAC) and VAC with alternate ifosfamide, etoposide (VAC + IE). Factors predictive of local failure and distant recurrence were analyzed. A total of 50 patients were analyzed. The median age at diagnosis was 14 years. Thirty-two patients were male, whereas 18 were female. Approximately, 95% of the patients relapsed after a median time gap of 1.6 years. The median 5-year disease-free survival was 30%. Systemic treatment with VAC or VAC + IE–based chemotherapy had equal local control and distant control rates. Smaller tumors had a better local control and lesser systemic failure than those of larger sizes. Successful treatment of Ewing's sarcoma requires optimal systemic and local therapy. Both the chemotherapy regimens showed equal survival rates. Control of both the local and distant diseases is a result of the combined modality approach. Stage at presentation is the most important factor for prognosis. Complete surgery and local radiotherapy are important predictive factors for local and systemic control.

Skin revitalisation: an exploration of the methods used in aesthetic dermatology

Skin can be revitalised and given ‘new life’ following the use of pioneering products and provision of aesthetic treatments. The aim of revitalising treatments is to make the skin appear younger, firmer, brighter and more flawless. Every patient's skin is unique and their treatment plan must be personalised. The aims and expectations of treatment must be established during the consultation using effective assessment techniques. A combined modality approach to skin rejuvenation will achieve the most effective results. This article will clarify the processes of assessment and skin type classification. It will also explore the benefits of cosmeceutical products used in conjunction with popular aesthetic procedures, such as skin peels, to maximise outcomes.

Options for Adjuvant Therapy for Uterine Leiomyosarcoma.

Uterine leiomyosarcoma (uLMS) is a rare disease; in the data from the SEER database, 3165 cases of uLMS were diagnosed between January 2000 and December 2012. While a majority of patients (60%) are diagnosed with early stage disease, recurrence rates are high. Five-year disease-specific survival is 76% for patients with FIGO stage I and 60% for patients with FIGO stage II disease. Adjuvant treatments, including radiation therapy, chemotherapy, and combined modality approaches, have been explored with the goal of demonstrating improved survival. However, heterogeneous patient populations, small sample sizes, and lack of no-treatment control arms have limited the interpretation and reliability of the results from these studies. A randomized trial of adjuvant pelvic radiation compared to no additional treatment showed that adjuvant radiation did not improve recurrence or survival outcomes for early-stage uterine LMS. To date, no prospective, randomized trial has been completed comparing adjuvant chemotherapy to observation. A recent well-designed retrospective study showed that women treated with adjuvant gemcitabine-docetaxel had no improvement in progression-free or overall survival compared to women who received no additional treatment. Thus, current data support our recommendation against adjuvant radiation or chemotherapy treatment for patients with non-morcellated, completely resected, and uterine-confined leiomyosarcoma. We recommend that these patients be observed with periodic surveillance imaging and physical examinations.

Combined chemoradiation for head and neck region myxofibrosarcoma of the maxillary sinus.

Adult sarcomas of the head and neck region (HNSs) are considered a rare clinicopathological entity. They account for only 2-15% of all adult sarcomas and for less than 1% of all head and neck malignancies. The preferred initial treatment option is wide surgical excision. Whenever surgery is considered infeasible, a frontline combined-modality approach including radiotherapy and chemotherapy might be proposed. We here report on a case of localized sarcoma of the maxillary sinus treated with induction chemotherapy and subsequent intensity-modulated radiation therapy (IMRT), achieving a persistent complete remission status. A 66-year-old man was referred to our institution hospital for left-sided facial pain with swollen left cheek and ipsilateral facial palsy. Magnetic resonance imaging showed a mass within the left maxillary sinus extending to the orbital floor and adjacent alveolar bones. Histological examination of the biopsy specimen demonstrated a myxofibrosarcoma. The patient underwent induction chemotherapy with gemcitabine 900 mg/m2 (days 1-8) and taxotere 80 mg/m2 every 3 weeks for 3 cycles and sequential simultaneous integrated boost (SIB) IMRT up to a total dose of 70 Gy/35 fractions to the macroscopic disease with 59.5 Gy/35 fractions to the level IB-II lymph nodes in the left neck. Treatment was well tolerated with mild acute toxicity. Complete remission was achieved at restaging MRI 6 months after the end of the combined modality approach. The patient remains in complete, unmaintained clinical and instrumental complete remission 18 months after treatment, with no late side effects. Combination therapy with induction chemotherapy and sequential SIB-IMRT could therefore be a promising modality for head and neck sarcomas, allowing for simultaneous tumor control and normal tissue sparing.

Leptomeningeal metastasis from prostate cancer.

Metastatic prostate carcinoma commonly involves bones and extrapelvic lymph nodes, with occasional visceral deposits. Central nervous system involvement is unusual and particularly the occurrence of leptomeningeal metastasis (LM) is extremely rare, with few cases described in the medical literature. The clinical presentation is characterized by multifocal neurological deficit and the prognosis is generally dismal, with survival ranging between 3 and 6 months. We report on a patient affected by LM due to prostate cancer who was treated with a combined-modality approach consisting of sequential chemotherapy and radiotherapy. A 70-year-old man was referred to our group for cognitive mental disorder, left-sided frontal headache and nausea; the patient had a previous history of metastatic prostate cancer. LM was diagnosed neuroradiologically with brain MRI and evidence of a detectable level of PSA in the cerebrospinal fluid. He was treated with docetaxel and prednisone for 3 cycles followed by external beam radiotherapy (EBRT) to the whole brain to a total dose of 30 Gy in 10 fractions with a simultaneous integrated boost to the macroscopic disease (total dose of 35 Gy in 10 fractions). No acute toxicity was observed. A substantial clinical response was obtained after EBRT with neurological improvement and radiologically stable disease at post-treatment imaging until 10 weeks after radiation. The patient died of sudden general condition deterioration 3 months after EBRT. Since LM derived from prostate cancer is likely to become a more common clinical event, such patients would need to be included in clinical trials evaluating new therapeutic approaches, considering that the current treatment strategies have been shown to be rather ineffective.

Association of chemotherapy and radiotherapy for T3N0 nasopharyngeal carcinoma in the area of intensity-modulated radiation therapy

Nasopharyngeal carcinoma (NPC) is a highly radiosensitive tumor (especially non-keratinizing carcinoma) and radiotherapy (RT) is the mainstay of treatment for newly diagnosed tumors. For early stage NPC, RT alone is the standard treatment while for locally advanced (LA) NPC concurrent chemoradiotherapy (CRT) with or without sequential chemotherapy [induction chemotherapy (IC) or adjuvant chemotherapy] is the standard treatment modality according to current guidelines, while the benefit of adjuvant or induction chemotherapy alone in addition to RT is limited (1,2). Indeed, the benefit of a combined modality approach has been demonstrated by several randomized trials and individual patient data meta-analysis (3). Moreover, in the Meta-Analysis of Chemotherapy in Nasopharynx Carcinoma (MAC-NPC) that included data on 4,806 patients in nineteen trials, with a median follow-up of 7.7 years, the addition of chemotherapy to RT significantly improved overall survival with an absolute benefit at 5 years of 6.3% (95% CI, 3.5–9.1%).

Treatment outcome of postoperative radiotherapy for squamous cell carcinoma of the head and neck

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; Though early stage malignancy of head and neck can be cured by surgery or radiotherapy, cure of patients with locally advanced disease continues to pose a therapeutic challenge. Loco regional failure is the major cause of death in head and neck cancer. As the cure of locally advance head and neck cancer is less than expectation, a combined modality approach is generally used in these type of patients. The combination of surgery, radiotherapy and chemotherapy can improve outcome in locally advance head and neck cancer.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; This observational study reviewed cancer patients reported in our hospital with the following inclusion criteria: primary head and neck cancer, treatment with radical surgery, and multiple nodal metastases. The prescribed dose of postoperative radiotherapy was 60–66 Gy. Patient characteristics, treatment parameters and clinical outcome were recorded. &lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; The primary end point was overall survival, and the secondary endpoint was disease status.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; Concurrent postoperative administration of chemotherapy and radiotherapy is a way to intensify treatment for resectable high-risk head and neck tumors.&lt;/p&gt;

Phase I/II trial of combined kyphoplasty and intraoperative radiotherapy in spinal metastases

Background ContextSpinal metastases occur in 30%–50% of patients with systemic cancer. The primary goals of palliation are pain control and prevention of local recurrence. PurposeThis study aimed to test the safety and efficacy of a combined modality approach consisting of kyphoplasty and intraoperative radiotherapy (Kypho-IORT). Study Design/SettingKyphoplasty and intraoperative radiotherapy was a prospective, single-center phase I/II trial. Patients were enrolled in a classical 3+3 scheme within the initial phase I, where Kypho-IORT was applied using a needle-shaped 50 kV X-ray source at three radiation dose levels (8 Gy in 8-mm, 8 Gy in 11-mm, and 8 Gy in 13-mm depth). Thereafter, cohort expansion was performed as phase II of the trial. The trial is registered with clinicaltrials.gov, number NCT01280032. Patient SamplePatients aged 50 years and older with a Karnofsky Performance Status of at least 60% and with one to three painful vertebral metastases confined to the vertebral body were eligible to participate. Outcome MeasuresThe primary end point was safety as per the occurrence of dose-limiting toxicities. The secondary end points were pain reduction, local progression-free survival (L-PFS), and overall survival (OS). MethodsPain was measured using the visual analog scale (VAS) and local control was assessed in serial computed tomography or magnetic resonance imaging scans. ResultsNone of the nine patients enrolled in the phase I showed dose-limiting toxicities at any level and thus, 52 patients were subsequently enrolled into a phase II, where Kypho-IORT was performed at various dose levels. The median pain score significantly dropped from 5 preoperatively to 2 at the first postoperative day (p<.001). Of 43 patients who reported a pre-interventional pain level of 3 or more, 30 (69.8%) reported a reduction of ≥3 points on the first postoperative day. A persistent pain reduction beyond the first postoperative day of ≥3 points was seen in 34 (79.1%) patients. The 3, 6, and 12 month L-PFS was excellent with 97.5%, 93.8%, and 93.8%. The 3, 6, and 12 months OS was 76.9%, 64.0%, and 48.4%. ConclusionKyphoplasty and intraoperative radiotherapy is safe and immediately provided sustained pain relief with excellent local control rates in patients with painful vertebral metastases.