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INTERNATIONAL JOURNAL OF HYPERTHERMIA 447
A complete blood count (CBC) and serum urea and cre-

atinine analysis were required from all patients on the day of
treatment, and full dose chemotherapy was administered
only when the neutrophil count was >2000/lL, platelet
count was >100 000/lL and hemoglobin was >9.0 g/dL.
Carboplatin dosage was calculated using the Calvert formula
before each chemotherapy session, based on creatinine val-
ues using the Cockcroft-Gault formula. In case of neutro-
penia, anemia and/or thrombocytopenia, treatment was
postponed for approximately a week and supportive treat-
ments as well as granulocyte-colony stimulating factors (G-
CSF) were administered for 3 consecutive days. CBCs and
blood biochemistry analyses, including renal function tests,
were repeated in each patient at least once weekly. Red
blood cell (RBC) transfusions and platelet transfusions were
given when values below the specified thresholds were
detected. Carboplatin and paclitaxel doses were reduced by
20–25% only during the subsequent treatment. In case of
severe myelosuppression, unacceptable toxicity, deterioration
of performance status or multiple delays, schedule individual-
ization was allowed and doses were reduced up to 30%.
Primary prophylaxis with G-CSF was not given.
Chemotherapy was mostly administered in an outpatient set-
ting; however, patients were hospitalized in case of Grade 3
or febrile neutropenia or Grade 3–4 infection.
Figure 2. Placement of hyperthermia electrode. View from left (A) and Patients that achieved complete response (CR), partial
above (B). response (PR) or stable disease (SD) status continued to
receive maintenance therapy with the same regimen until
death. Those with progressive disease were assigned to
in doses ranging between 5 and 20 IU (in order to achieve a second-line chemotherapy with a single agent such as erloti-
state of mild hypoglycemia with blood glucose levels around nib, gemcitabine, or docetaxel. Patients with ALK fusion
50–60 mg/dl for normoglycemic patients and in accordance received targeted therapy as second-line treatment following
with MSCT protocols) [24–26]. progression after chemotherapy.
Patients visited our clinic for treatment sessions following
12 h of fasting, and their blood glucose level was measured
Ketogenic diet, hyperthermia and hyperbaric
upon admission. Then this level was down-titrated to the tar-
oxygen therapy
geted pretreatment mild hypoglycemia level with insulin
administration. An IV line for dextrose administration was Patients were encouraged to consume a ketogenic diet,
always kept open. Patients were closely monitored for hypo- which is high in fat and low in carbohydrate. However, it is a
glycemia signs/symptoms and blood glucose levels by the mild rather than a strict ketogenic diet, where patients avoid
attending physician and an experienced nurse. In normogly- food with a high amount of carbohydrates. Every patient
cemic patients, fasting blood glucose levels upon admission received a brief training regarding the diet restrictions and
ranged between 70 and 90 mg/dl, while the achieved pre- was given a food list. All patients were asked to keep a diet-
treatment glucose ranged between 50 and 59 mg/dl. For dia- ary record. In addition to proactively encouraging and ques-
betics on the other hand, a more individualized approach tioning the patient for the ongoing ketogenic diet, blood
was adopted. In diabetics (14 patients, none of which were sugar levels were measured as a part of routine procedures
on insulin and all were on oral anti-diabetic therapy) blood before insulin administration at each visit. Based on blood
glucose level was lowered to around 90 mg/dl based on the sugar levels and dietary records (if the patient was able to
individual patient’s condition. All diabetic patients were man- complete successfully), a feedback was given to the patient
aged together with endocrinology specialist support. Fasting at each visit on how effective the diet was and what modifi-
blood glucose levels ranged between 95 and 160 mg/dl for cations or precautions are still required.
diabetic patients. For these patients, the achieved pretreat- For each 60-min hyperthermia session, OncoTherm EHY-
ment levels ranged between 65 and 95 mg/dl. Following the 3010 HT device (OncoTherm, Troisdorf, Germany) was used
achievement of target blood sugar level, treatment was initi- to gradually increase the temperature of the tumoral region.
ated together with oral sugar intake. All patients received a Thoracic tumors and thoracic metastases were targeted. A
chemotherapy regimen consisting of paclitaxel 75 mg/m2 large enough mobile electrode positioned over the tumoral
(over 60 min) and carboplatin AUC 2 (after paclitaxel, region was used based upon each individual patient’s condi-
over 30 min). tion to cover the primary tumor and thoracic metastases (if

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INTERNATIONAL JOURNAL OF HYPERTHERMIA 447

A complete blood count (CBC) and serum urea and cre-

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