Regimens of neo-adjuvant chemotherapy in the treatment of breast cancer: A systematic review & network meta-analysis with PRISMA-NMA compliance.

Efficacy of neo-adjuvant therapy depends on the used regimens. There are contradictory findings regarding relative efficacy of these regimens. Accordingly, present study assessed the relative efficacy of Anthracyclines, Taxanes and added targeted therapies in neo-adjuvant setting simultaneously with a focus on tumor response and breast conserving surgery among breast cancer patients. The network meta-analysis model was used. Ranking of treatment was done by surface under cumulative ranking curve for each regimen. Out of 1286 screened records obtained by searching PubMed and Cochrane register of controlled trials, a total of 34 studies randomizing 12,630 breast cancer patients were included. Network meta-analysis for pathological complete response (pCR) revealed Addition of targeted therapies especially Trastuzumab for HER2+ breast cancer and Bevacizumab for HER2- breast cancer along with Anthracyclines and/or Taxanes based chemotherapy significantly improves pCR but with increased haematological toxicities. All the regimens performed similar in terms of breast conserving surgery rates.

Low dose radiation primed iNOS + M1macrophages modulate angiogenic programming of tumor derived endothelium.

Solid tumors are covered by stroma, which is hypoxic in nature and composed of various non-malignant components such as endothelial cells, fibroblasts, and pericytes that support tumor growth. Tumor stroma represents a mechanical barrier for tumor infiltration of CD8+ effector T cells in particular. In this context, our previous studies have demonstrated the therapeutic impact of Low-Dose Radiation (LDR)-primed and M1-retuned (iNOS+) peritumoral macrophages that produce inducible nitric oxide, have immunological roles on tumor infiltration of effector T cells, cancer-related inflammation, and subsequent tumor immune rejection in a mouse model of pancreatic cancer. These findings suggested a possible modification of tumor endothelium by LDR-primed macrophages. In line with these observations, here we demonstrate the influence of LDR in down-modulating HIF-1 in irradiated tumors in the course of polarization of irradiated tumor-associated macrophages toward an M1 phenotype. Furthermore, we demonstrate that M1 macrophages which are primed by LDR can directly influence angiogenic responses in eNOS+ endothelial cells which produce nitric oxide having both vascular and physiological roles. Furthermore, we demonstrate that naïve macrophages, upon differentiating to an M1 phenotype either by Th1 stimuli or LDR, potentially modify sphingosine-1-phosphate/VEGF-induced angiogenic signaling in tumor-derived endothelial cells with tumorigenic potential, thus indicating the significance of iNOS+ macrophages in modulating signaling in eNOS+ tumor-derived endothelium. Our study suggests that iNOS+ macrophages can activate tumor endothelium which may contribute to cancer-directed immunotherapy in particular.

Primary pediatric mid-brain lymphoma: Report of a rare pediatric tumor in a rare location.

Primary central nervous system lymphoma (PCNSL) is a rare disease in pediatric age group. A thirteen-year-old male child presented with complaints of headache for six months, vomiting and diplopia for three days. Magnetic resonance imaging of the brain showed a single lesion of 1.7 cm × 1.6 cm × 1.6 cm in the mid brain and tectum. He underwent a gross total resection of the tumor. The histopathological evaluation revealed B cell high grade non Hodgkin lymphoma. The patient was treated with High dose methotrexate and cranio spinal radiation. The patient was alive without disease 12 mo after completion of treatment. This case highlights importance of keeping PCNSL as differential in brain stem lesions of pediatric patients also. Radiation and chemotherapy remains the most important treatment for such patients.

Malignant and borderline phyllodes tumor of breast treated with a multi-modality approach in a tertiary cancer care centre in North India.

BACKGROUND: Phyllodes tumor (PT) of the breast can be categorized into benign, borderline and malignant subgroups depending on various histopathological factors. Although malignant PTs may be indolent and controlled by local excision, they frequently show local and distant relapses. Literature reveals local recurrence to be the predominant pattern of failure and thus emphasizes the importance of adjuvant radiation in these tumors. The role of systemic chemotherapy has remained doubtful. MATERIALS AND METHODS: We have analyzed details of all patients of PT (n = 33) treated with adjuvant multi-modality approach in our institute since 1994-2009. The demographic data, treatment details, recurrence patterns and salvage treatment options were documented. RESULTS: All patients received adjuvant radiation. Seven patients received adjuvant chemotherapy. The mean survival of the entire cohort was 150.618 months. There was a trend for better overall survival with borderline grade (193.6 vs. 160.2 months; P = 0.08, log rank). The disease free survival (DFS) favored borderline grade (193.6 months vs. 82.9 months for high grade; P = 0.02, log rank). The DFS was significantly better in tumors having negative margins on postoperative histopathological examination (DFS rate at 5 years being 100% vs. 69.2% for positive or close margins; P = 0.015). The mode of surgery did not have any impact on survival. CONCLUSION: Adjuvant Radiation should be discussed taking into account surgical margins, size and various pathological factors of the primary. Adjuvant radiation may be utilized in high risk patients to enhance loco-regional control. Systemic chemotherapy is an option, worth exploring, in cases of systemic failure.

Short course palliative radiotherapy in the management of choroidal metastasis: An effective technique since ages.

PURPOSE: Uveal tract is the most common site of intra-ocular metastasis. Overall, the reported prevalence of clinically evident uveal metastases in patients with cancer ranges from 2% to 9%, with the majority of the cases being due to breast cancer. We aimed at evaluating the role of palliative radiotherapy in the management of choroidal metastasis from carcinoma breast. MATERIALS AND METHODS: We describe the clinico-pathologic features, treatment and outcome of ten patients of carcinoma breast who presented to the ophthalmology department at our institution with ocular symptoms attributable to choroidal metastasis. RESULTS: Nine of the patients were female while one was male. All of them presented with painless progressive diminution of vision. Median duration of symptoms was 2.25 months. Five patients had associated lung metastasis while bone and brain metastases were seen in three and two patients respectively. All of them received palliative radiotherapy (RT) to the involved eye (or eye+brain) by 3D-CRT (n=7), or 2 Dimensional technique (n=2) or electron therapy (n=1). Doses prescribed were 30 Gy/10#/2 weeks (n=8); 20 Gy/5 #/1 week (n=2). Simultaneously they received hormonal therapy (n=6) or systemic chemotherapy (n=3). After a median follow up of 18 months seven patients had complete resolution and two patients had partial resolution of the metastases. CONCLUSION: Short course palliative radiation therapy is an effective modality for the management of choroidal metastasis in patients of carcinoma breast. In the current report it led to formidable local control with acceptable radiation induced toxicity.

Passive Smoking and Breast Cancer - a Suspicious Link.

BACKGROUND: Breast cancer is the most common malignancy of women in the world. The disease is caused by infectious and non-infectious, environmental and lifestyle factors. Tobacco smoke has been one of the most widely studied environmental factors with possible relevance to breast cancer. The purpose of this study was to assess the impact of tobacco smoking in breast cancer patients in a hospital based cohort and to establish prognostic implications if any. MATERIALS AND METHODS: A retrospective audit of 100 women with pathological diagnosis of invasive breast cancer was included in this study. The verbal questionnaire elicited information on current and previous history of exposure to smoking in addition to active smoking. All analyses were adjusted for potential confounders, including stage at presentation, alcohol intake, hormonal replacement therapy, oral contraceptive intake, obesity and menopausal status. RESULTS: The mean age at presentation of breast cancer was 51.4 ± 10.86 years. Mean age of presentation was 53.1±11.5 and 45.7±11.9 years in never smokers and passive smokers, respectively. Age at presentation varied widely in patients exposed to tobacco smoke for >10 years in childhood from 40.3± 12.0 years to 47.7± 13.9 in patients exposed for > 20 years as adults. Among passive smokers, 60.9% were premenopausal and 39.1% of patients were postmenopausal. In never smokers, 71.4% were post menopausal. Expression of receptors in non-smokers vs passive smokers was comparable with no significant differences. Metastatic potential in lung parenchyma was slightly elevated in passive smokers as compared to never smokers although statistically non-significant. CONCLUSIONS: An inverse relationship exists between the intensity and duration of smoking and the age at presentation and poor prognostic factors. The results strongly suggest efforts should be taken to prevent smoking, encourage quitting and restrict exposure to second hand smoke in India.

Medullomyoblastoma treated with craniospinal radiation and adjuvant chemotherapy: Report of 4 cases and review of the literature.

Medullomyoblastoma (MMB) is a rare primitive neuro-epithelial tumor and seen in mainly pediatric age group1. There have been about 50 cases reported so far in the literature. In this report, we describe the clinical features and treatment of 4 cases of MMB.

Metastatic Adenocarcinoma of Prostate in a 28-Year-Old Male: The outcome is poor in young patients?

Prostate cancer is common in older patients. Rarity in younger population limits the study of natural history and prognosis in this population. Most of the published data has reported poor outcome in younger patients with metastatic prostate cancer. Here, we report a case of prostate cancer in 28-year-old male who presented with bone metastasis. After bilateral inguinal orchidectomy, he was started on anti-androgen therapy and received palliative radiotherapy for bone metastasis. There was only a slight decrease in prostate-specific antigen (PSA) level and pelvic disease post treatment. Subsequently, he was started on opioid analgesics (by World Health Organization, WHO, step ladder) in view of persistent pain. The index case is being presented for its rarity and probable poor outcome in young patients and to stress on the fact that the possibility of primary prostatic adenocarcinoma should be investigated in a male presenting with bone metastasis irrespective of the age.

Radiation induced lung injury: prediction, assessment and management.

Radiation induced lung injury has long been considered a treatment limiting factor for patients requiring thoracic radiation. This radiation induced lung injury happens early as well as late. Radiation induced lung injury can occur in two phases viz. early (<6 months) when it is called radiation pneumonitis and late (>6 months) when it is called radiation induced lung fibrosis. There are multiple factors that can be patient, disease or treatment related that predict the incidence and severity of radiation pneumonitis. Radiation induced damage to the type I pneumocytes is the triggering factor to initiate such reactions. Over the years, radiation therapy has witnessed a paradigm shift in radiation planning and delivery and successfully reduced the incidence of lung injury. Radiation pneumonitis is usually a diagnosis of exclusion. Steroids, ACE inhibitors and pentoxyphylline constitute the cornerstone of therapy. Radiation induced lung fibrosis is another challenging aspect. The pathophysiology of radiation fibrosis includes continuing inflammation and microvascular changes due to pro-angiogenic and pro- fibrogenic stimuli resembling those in adult bronchiectasis. General supportive management, mobilization of airway secretions, anti-inflammatory therapy and management of acute exacerbations remains the treatment option. Radiation induced lung injury is an inevitable accompaniment of thoracic radiation.

Outcome of surgery and post-operative radiotherapy for major salivary gland carcinoma: ten year experience from a single institute.

AIMS: To determine the clinical characteristics, pathological features, local and distant failure patterns in patients with carcinoma of major salivary glands treated with surgery and postoperative radiotherapy (PORT). MATERIALS AND METHODS: We retrospectively reviewed 106 cases of major salivary gland tumor seen at our centre (1998-2008). Sixty five cases of major salivary gland carcinoma were selected for analysis (exclusions: benign, palliative, non-carcinomas). The patient population treated by surgery and PORT was divided into two groups: 1) Patients who underwent surgery and immediate PORT (Primary PORT); 2) Patients with recurrent carcinoma who underwent at least two surgeries and received PORT in the immediate post-operative period of the last performed surgery (Recurrent PORT). Recurrence free survival (RFS) was assessed using the Kaplan-Meier method. RESULTS: Median age was 35 years with a male: female ratio of 1.3:1. The majority of cancers were located in the parotid gland (86.2%) and the most common histology was mucoepidermoid carcinoma (43%). Thirty nine cases (60%) were primary while 26 (40%) were recurrent. Optimal surgery was performed in 59/65 patients (90.8%). 43 patients (66.2%) underwent neck dissection, of which 14 (32.5%) had nodal metastasis. Overall, 61 (93.8%) patients complied with the prescribed radiotherapy. Median dose of PORT was 60 Gy. Median follow-up was 13.1 months (range 2-70). Relapse free survival was 50.4% at 60 months. Some 12 cases (18.5%) recurred with a median time to recurrence of 16.9 months. CONCLUSIONS: Surgery and PORT is an effective treatment for major salivary gland carcinoma with over 90% compliance and <20% recurrence. Early treatment with postoperative radiotherapy may increase the survival rate in major salivary gland carcinoma patients.

Advantages and implications of high dose rate (HDR) total skin electron irradiation (TSEI) for the management of Mycosis Fungoides. Indian experience.

BACKGROUND: Mycosis Fungoides (MF) is an indolent lymphoproliferative disorder affecting dermis caused by abnormal proliferation of CD4+ T-cells. Radiation therapy is the most effective modality of treatment for MF which offers cure in limited stage disease and desirable palliation in advance stage disease. Treating entire skin having many curved surfaces and folds with radiation is the real challenge for the radiation oncologist. Many techniques, dose schedules and modifications in total skin electron irradiation (TSEI) have been tried since 1950s. TSEI treatment is a very time consuming, inconvenient and physically challenging to both patient as well as oncologist. AIM: At our center TSEI was performed since 1983 with conventional linear accelerator where the treatment time was prolonged beyond two hours, which was very difficult or the patient, oncologist, technical officer and eating away the machine time hampering the treatment of other patients. From 1998 we shifted to high dose rate (HDR) mode, in order to bring down the treatment time of a single patient every day from two and half hour to 15 min. The reduction of treatment time increases patient compliance and at the same time saved machine time. MATERIALS AND METHODS: Between 1998 and 2003, eleven pathological diagnosed MF patients were treated using HDR TSEI. All the patients were male between 40 and 70 years of age, who had the history of having the disease for 7-22 months. Four patients had T2 and seven patients had T3 stage disease with more than 90% skin surface involvement. TSEI was performed with 4 MeV electrons with a daily fraction size of 120 cGy to a total dose of 36 Gy. At the end of 36 Gy, boost dose of 10 Gy was delivered to self shielding regions like sole, scalp and perineum. Considering the treatment related toxicities and consequent treatment interruptions, in the first seven patients, the last four patients were treated using similar HDR TSEI technique with modified treatment schedule, where the treatment was given on an alternate day basis following 2nd week of initiation of treatment. RESULTS: The patients were followed over a period of 144 months with a median of 72 months. Nine patients are alive without any evidence of disease, one patient relapsed and one died due to progression of disease. The most common radiation related morbidities are erythema, skin blisters, various degree of desquamations, swelling of joints (specially small joints) etc. which are controlled by treatment interruptions and conservative measures. By modifying the treatment schedule, the incidence of toxicity as well as treatment interruptions were brought down. CONCLUSIONS: We can conclude that HDR-TSEI is an excellent and safe therapeutic modality for the patients with MF both curative as well as palliative without any added toxicity profile, provided patient positioning is done properly.

Sarcomatoid squamous cell carcinoma of uterine cervix: pathology, imaging, and treatment.

Sarcomatoid squamous cell carcinoma of the cervix is a rare tumor. Only 16 cases have so far been reported in literature. We report here one such tumor occurring in a 54-year-old postmenopausal woman. Our case report describes the clinical, pathological, and PET scan characteristics of this tumor. The patient was treated with concurrent chemoradiotherapy and is disease free at 6-months follow-up.

A phase II study of gemcitabine and carboplatin combination chemotherapy in gallbladder carcinoma.

BACKGROUND: Patients with carcinoma of the gallbladder have advanced, unresectable tumor at the time of presentation and face a dismal prognosis in the absence of a standard palliative chemotherapy regimen. This study was undertaken to evaluate the efficacy and safety of combined chemotherapy of gemcitabine and carboplatin in 20 patients with advanced gallbladder carcinoma. METHODS: The criteria of eligibility included chemonaive patients with unresectable gallbladder cancer, bidimensionally measurable disease, Zubrod's performance status < or = 2, and adequate major organ function. The patients received gemcitabine (1000 mg/m2) on days 1 and 8, and carboplatin (target AUC of 5.0 mg/ml) on day 1, in a 21-day cycle. CT was used for response assessment. RESULTS: In this group of 20 patients with advanced gallbladder carcinoma 6 were men and 14 women, with a median age of 55 years. The stage of the tumor at presentation was IVB in 14 patients (70%), IVA in 3 (15%) and III in 3 (15%). Four patients (21%) achieved a complete response, and 3 (15.7%), a partial response; an overall response rate was 36.7%. The median time to progression of the tumor was 33.8 weeks, and 1-year survival rate of the patients was 43.3%. Anemia of WHO grade III or IV was seen in 2 patients (10%) and 1 patient (5%), respectively. Grade III neutropenia and thrombocytopenia were observed in 2 patients (10%) and 1 patient (5%), respectively. CONCLUSION: With mild toxicity, combined chemotherapy of gemcitabine and carboplatin is effective in the treatment of advanced gallbladder carcinoma.